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Sample records for preoperative imatinib treatment

  1. Imatinib treatment for gastrointestinal stromal tumour (GIST).

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    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.

  2. Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: a proof-of-concept study in the preoperative window period (ImPACCT).

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    Ubink, I; Bloemendal, H J; Elias, S G; Brink, M A; Schwartz, M P; Holierhoek, Y C W; Verheijen, P M; Boerman, A W; Mathijssen, R H J; de Leng, W W J; de Weger, R A; van Grevenstein, W M U; Koopman, M; Lolkema, M P; Kranenburg, O; Borel Rinkes, I H M

    2017-04-19

    than non-selected patients with late-stage disease. By making use of the pre-operative window period, the biological effect of imatinib treatment on CMS4 tumours can be rapidly assessed. Delivering proof-of-concept for drug action in early stage disease should form the basis for the design of future trials with subtype-targeted therapies in colon cancer patients. ClinicalTrials.gov: NCT02685046 . Registration date: February 9, 2016.

  3. Imatinib as preoperative therapy in Chinese patients with recurrent or metastatic GISTs

    Institute of Scientific and Technical Information of China (English)

    Chunmeng Wang; Biqiang Zheng; Yong Chen; Xi Cao; Ruining Zhang; Yingqiang Shi

    2013-01-01

    Imatinib has dramatically altered the options for management of patients with gastrointestinal stromal tumours.However,it has become clear that secondary resistance to the drug develops during long-term therapy.The purpose of our study was to retrospectively analyze safety and long-term outcomes in Chinese patients with recurrent or metastatic GISTs treated with imatinib preoperatively.Methods:Between June 2003 and June 2011,22 patients underwent surgery for recurrent or metastatic GISTs after preoperative treatment with imatinib.Results:Complete resection was accomplished in 8 of the 10 responsive disease (RD) patients (80%),and in 3 of the 12 patients (25%) who had progression disease (PD).The amount of blood loss during the operation in PD patients was higher than in RD patients.There was 1 hospital death in PD group related to surgery,while the other patients recovered with conservative therapy because complications were mild.The difference in median PFS between patients with RD and those with PD was significant (24.8 vs.2.81 months,P<0.001).The difference in 2-year OS rate between patients with RD and those with PD was not significant (100% vs.87.5%,P>0.05).Conclusions:Our study indicates that surgical intervention can improve the PFS of Chinese patients with recurrent or metastatic GISTs responsive to imatinib,but does not prolong OS as well as in patients who develop imatinib resistance.Surgical resection following imatinib treatment is feasible and can be considered for patients with advanced GISTs responsive to imatinib.

  4. Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia

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    Daniels, J. M. A.; Vonk-Noordegraaf, A.; Janssen, J. J. W. M.; Postmus, P. E.; van Altena, R.

    Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are

  5. An analysis of strategic treatment interruptions during imatinib treatment of chronic myelogenous leukemia with imatinib-resistant mutations.

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    Paquin, Dana; Sacco, David; Shamshoian, John

    2015-04-01

    Chronic myelogenous leukemia (CML) is a cancer of the white blood cells that results from increased and uncontrolled growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. The most common form of treatment for CML is imatinib, a tyrosine kinase inhibitor. Although imatinib is an effective treatment for CML and most patients treated with imatinib do attain some form of remission, imatinib does not completely eradicate all leukemia cells, and if treatment is stopped, all patients eventually relapse (Cortes, 2005). In Kim (2008), the authors developed a mathematical model for the dynamics of CML under imatinib treatment that incorporates the anti-leukemia immune response, and in Paquin (2011), the authors used this mathematical model to study strategic treatment interruptions as a potential therapeutic strategy for CML patients. Although the authors presented the results of several numerical simulations in Paquin (2011), the studies in that work did not include the possibility of imatinib-resistant mutations or an initial population of imatinib-resistant leukemia cells. As resistance is a significant consideration in any drug treatment, it is important to study the efficacy of the strategic treatment interruption plan in the presence of imatinib resistance. In this work, we modify the delay differential equations model of Kim (2008), Paquin (2011) to include the possibility of imatinib resistance, and we analyze strategic treatment interruptions as a potential therapeutic tool in the case of patients with imatinib-resistance leukemia cells.

  6. Dramatic regression and bleeding of a duodenal GIST during preoperative imatinib therapy: case report and review

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    Schwandner Thilo

    2010-06-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GISTs are the most common mesenchymal tumors of the digestive tract. The majority of GISTs is located in the stomach. Only 3-5% of GISTs are located in the duodenum associated with an increased risk of gastrointestinal bleeding as primary manifestation. With response rates of up to 90%, but complications like bleeding due to tumor necrosis in 3%, imatinib mesylate dramatically altered the pre- and postoperative therapy for GIST patients. Case presentation A 58-year-old female patient presented with acute upper gastrointestinal bleeding 2 weeks after a giant GIST of the duodenum had been diagnosed. Neoadjuvant imatinib therapy had been initiated to achieve a tumor downsizing prior to surgery. During emergency laparotomy a partial duodenopancreatectomy was performed to achieve a complete resection of the mass. Histology revealed a high-malignancy GIST infiltrating the duodenal wall. Adjuvant imatinib therapy was initiated. At follow-up (19 months the patient is still alive and healthy. Conclusion Giant GISTs of the duodenum are rare and - in contrast to other localizations - harbour a higher risk of serious bleeding as primary manifestation. Tumor necrosis and tumor bleeding are rare but typical adverse effects of imatinib therapy especially during treatment of high-malignancy GIST. In GIST patients with increased risk of tumor bleeding neoadjuvant imatinib therapy should thoroughly be performed during hospitalization. In cases of duodenal GIST primary surgery should be considered as treatment alternative.

  7. One-stage laparoscopic resection for a large gastric gastrointestinal stromal tumor and synchronous liver metastases following preoperative imatinib therapy: A case report.

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    Cao, Feng; Li, Jia; Li, Ang; Fang, Yu; Li, Fei

    2013-04-01

    Laparoscopic partial gastrectomy without lymph node dissection has been accepted worldwide for the treatment of small gastric gastrointestinal stromal tumors (GISTs). However, the role of laparoscopic surgery in the treatment of large gastric GISTs remains under debate due to the risk of tumor spillage or rupture of the tumor capsule leading to peritoneal seeding. To the best of our knowledge, one-stage laparoscopic resection for a large gastric GIST and synchronous liver metastases following preoperative imatinib therapy has not been previously reported. Here, we present our initial experience of this method of treatment.

  8. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

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    Waring Paul

    2004-10-01

    Full Text Available Abstract Background The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. Case presentation A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression

  9. Appropriate modulation of autophagy sensitizes malignant peripheral nerve sheath tumor cells to treatment with imatinib mesylate.

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    Okano, Munehiro; Sakata, Naoki; Ueda, Satoshi; Takemura, Tsukasa

    2014-04-01

    Malignant peripheral nerve sheath tumor (MPNST), very rare in childhood, is a highly aggressive soft-tissue tumor. We experienced a case of a 7-year-old boy with MPNST who was treated with imatinib mesylate (imatinib) after the identification of platelet-derived growth factor receptor expression in his tumor. We were unable to observe clinical benefits of imatinib in this patient. Therefore, cellular reactions of imatinib were investigated in vitro using 3 MPNST cell lines. Imatinib induced cytotoxicity in vitro with variable IC50 values (11.7 to >30 μM). Induction of apoptosis was not a pivotal mechanism in the inhibitory effects. We found that the treatment of MPNST cell lines with imatinib induced autophagy. Suppression of the initiation of autophagy by 3-methyladenine or small interfering RNA (siRNA) against beclin-1 attenuated the imatinib-mediated cytotoxicity. In contrast, blocking the formation of autophagosomes or the development of autolysosomes using siRNA against microtubule-associated protein light chain 3B, bafilomycin A1, chloroquine, or an MEK1/2 inhibitor (U0126) enhanced the imatinib-induced cytotoxicity in MPNST cells. Our data showed that the imatinib-mediated autophagy can function as a cytotoxic mechanism and that appropriate modulation of autophagy may sensitize MPNST cells to imatinib, which in turn may be a novel therapeutic strategy for MPNST.

  10. Successful pregnancy in a patient with chronic myeloid leukemia under treatment with imatinib.

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    Tsuzuki, Motohiro; Inaguma, Youko; Handa, Kousuke; Hasegawa, Akio; Yamamoto, Yukiya; Watanabe, Masato; Mizuta, Syuichi; Maruyama, Fumio; Okamoto, Masataka; Emi, Nobuhiko

    2009-01-01

    Contraception is recommended during imatinib therapy based on the teratogenicity data in rats. However, patients may become pregnant and here we describe a successful pregnancy and labor without any congenital anomaly in a patient with chronic myeloid leukemia (CML) under treatment with imatinib. The patient had received imatinib for 53 months before she became pregnant, with a complete cytogenetic response achieved after 6 months of therapy and a major molecular response (MMR) after 28 months. CML was in MMR at discovery of pregnancy and the fetus had been exposed to imatinib for 5 weeks. Treatment was discontinued, but MMR persisted during gestation.

  11. Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose

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    Waclaw J

    2015-09-01

    Full Text Available Joanna Waclaw,1 Tomasz Sacha,1 Tomasz Stoklosa,21Department of Hematology, Jagiellonian University Collegium Medicum, Kraków, 2Department of Immunology, Medical University of Warsaw, Warsaw, Poland Abstract: Imatinib was the first tyrosine kinase inhibitor (TKI, successfully used in a clinical setting. It inhibits activity of BCR-ABL1 oncogenic tyrosine kinase which is crucial in the pathogenesis of chronic myeloid leukemia (CML. The safety and efficacy of imatinib dose 400 mg daily was established in several clinical studies. Nevertheless, imatinib dose escalation (≥600 mg daily has been widely explored as an option to improve clinical outcomes. Results of the meta-analysis comparing frontline therapy with imatinib 400 mg daily vs high dose (HD, ≥600 mg daily in patients with chronic phase CML (CML-CP showed that the rate of complete cytogenetic response as well as major molecular response (MMR at 12 months was significantly higher in HD imatinib group. However, HD imatinib does not improve overall survival and progression-free survival. Thus, the routine use of HD imatinib as frontline treatment for CML-CP is not recommended. In patients with CML-CP resistant to standard dose, HD imatinib does not significantly improve patient outcomes without a prior cytogenetic response. Therefore, in second-line therapy, the current CML-CP treatment guidelines do not recommend imatinib dose escalation but the use of second-or third-generation TKIs. In the therapy of TKI-naïve patients with accelerated or blastic phase of CML, HD imatinib (400 mg twice daily is one of the recommended standards. In case of disease progression while on imatinib, second- or third-generation TKIs should be administered. Keywords: imatinib, standard dose, dose escalation, chronic myeloid leukemia, BCR-ABL1, high dose

  12. First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib

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    Rafiyath Shamudheen

    2010-11-01

    Full Text Available Abstract Imatinib, a tyrosine kinase inhibitor (TKI of BCR-ABL, was the standard first-line therapy for chronic myeloid leukemia (CML for almost 10 years. Dasatinib and nilotinib, two newer drugs with higher potency than imatinib against BCR-ABL and activity against most imatinib-resistant BCR-ABL mutations, have each shown superior efficacy compared with imatinib for first-line treatment of chronic-phase CML in randomized phase 3 trials. With 14 months follow-up time, available data suggest no obvious differences in efficacy between dasatinib and nilotinib. Compared with imatinib, dasatinib is associated with higher rates of pleural effusion and thrombocytopenia, but lower rates of edema, gastrointestinal AEs, musculoskeletal AEs, and rash. Nilotinib is associated with higher rates of dermatologic toxicity, headache, and biochemical abnormalities associated with hepatic and pancreatic toxicity compared with imatinib, but lower rates of edema, gastrointestinal AEs, muscle spasm, and neutropenia. Several studies have shown that poor adherence to imatinib detrimentally affects responses and should be considered in patients with a suboptimal response. The different dosing requirements of dasatinib (once daily with or without food and nilotinib (twice daily with fasting may be an additional factor in selecting frontline agents. This review compares and contrasts the three FDA approved first line TKI agents.

  13. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

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    Abe, Michio [Minamata City Hospital and Medical Center, Minamata City, Kumamoto 867 (Japan); Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina, E-mail: jbaranow@unmc.edu [Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, NE 68198 (United States)

    2011-05-25

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy.

  14. Influence of late treatment on how chronic myeloid leukemia responds to imatinib

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    Ana Carolina Costa Scerni

    2009-01-01

    Full Text Available INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil. BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60% probability of achieving MMR, while the probability for those patients who received late treatment was 40%. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79%, compared with patients who received early treatment (21%, odds ratio=5.75, P=0.012. The probability of maintaining MMR at 30 months of treatment was 80% in the early treatment group and 44% in the late treatment group (P=0.0005. CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.

  15. Partial response to imatinib treatment in a patient with unresectable gastrointestinal stromal tumor: A case report and mini literature review

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    Wu, Xiaolong; Feng, Libo; Liu, Qing; Xia, Dong; Xu, Liang

    2016-01-01

    The aim of the present study was to evaluate the efficacy and safety of imatinib mesylate in unresectable gastrointestinal stromal tumor (GIST) and to discuss its therapeutic regimen. A patient with unresectable GIST is described, and several key clinical studies are reviewed, including the clinical trials B2222 and S0033, which contain recently reported results of the long-term clinical outcome of imatinib in patients with unresectable or metastatic GIST. The recent results of the two studies demonstrate the long-term efficacy and safety of imatinib for unresectable or metastatic GIST. A positive response to imatinib treatment was observed in the present patient, which is consistent with the data of the B2222 and S0033 trials. However, further long-term, large-scale, multicenter and controlled trials are required to determine the relative efficacy of combining imatinib agents with surgical procedures or administering imatinib alone. PMID:27698727

  16. Leucemia Mielóide Crônica: causas de falha do tratamento com mesilato de imatinibe Chronic Myeloid Leukemia: causes of treatment failure with imatinib

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    Katia B. B. Pagnano

    2008-04-01

    Full Text Available O mesilato de imatinibe (MI é atualmente o tratamento de escolha da Leucemoa Mielóide Crônica (LMC, mas, apesar dos excelentes resultados, não é capaz de erradicar completamente a doença, podendo ocorrer resistência ao tratamento. O mecanismo mais conhecido de resistência é o desenvolvimento de mutações do BCR-ABL, que impedem a ação ligação adequada do imatinibe à quinase, além de amplificação gênica e evolução clonal. No entanto, há uma série de outros mecanismos envolvidos e ainda pouco estudados, como alterações na absorção, efluxo e influxo de droga para o interior das células. Devem-se também considerar outros fatores, como aderência ao tratamento e uso de medicamentos concomitantes que podem interferir com imatinibe, diminuindo sua ação. O entendimento desses mecanismos poderá contribuir no desenvolvimento de novas estratégias para o tratamento dos casos resistentes.Imatinib is currently the treatment of choice of CML, but despite of the excellent results, it is not able to completely eradicate the disease and resistance may occur. The most studied mechanism is the presence of ABL kinase mutations that interfere with imatinib binding and action, gene amplification and clonal evolution. However, there are other mechanisms involved and less studied such as drug absorption and influx and efflux of imatinib. Besides the true causes of resistance, compliance is always a concern and also drug interaction should be checked. An understanding of these mechanisms will certainly contribute to develop new strategies for the treatment of resistant cases.

  17. Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis.

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    Vincenzi, Bruno; Nannini, Margherita; Fumagalli, Elena; Bronte, Giuseppe; Frezza, Anna Maria; De Lisi, Delia; Spalato Ceruso, Mariella; Santini, Daniele; Badalamenti, Giuseppe; Pantaleo, Maria Abbondanza; Russo, Antonio; Dei Tos, Angelo Paolo; Casali, Paolo; Tonini, Giuseppe

    2016-10-25

    We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line.All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line.

  18. Approval summary: imatinib mesylate in the adjuvant treatment of malignant gastrointestinal stromal tumors.

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    Cohen, Martin H; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    On December 19, 2008, the U.S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec(R); Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal tumor (GIST). A randomized, double-blind, placebo-controlled study enrolling 713 patients was submitted. The primary objective of the clinical trial was to compare the recurrence-free survival (RFS) intervals of the two groups. Overall survival (OS) was a secondary endpoint. Eligible patients were > or =18 years of age with a histological diagnosis of GIST (Kit(+)), resected tumor size > or =3 cm, and a complete gross resection within 14-70 days prior to registration. Imatinib, 400 mg orally, was administered once daily for 1 year. The study was terminated after completion of the third protocol-specified interim analysis. At that time, 100 RFS events were confirmed by a blinded central independent review. With a median follow-up of 14 months, 30 RFS events were observed in the imatinib group and 70 were observed in the placebo group (hazard ratio, 0.398; 95% confidence interval, 0.259-0.610; two-sided p-value or =3 adverse reactions. The most frequently reported adverse reactions (> or =20%) were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Drug was discontinued for adverse reactions in 17% and 3% of the imatinib and placebo-treated patients, respectively.

  19. Usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in dermatofibrosarcoma protuberans on treatment with imatinib

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    Kashyap, Raghava; Muddu, Vamshi Krishna; Anantamakula, Sameera; Sri, Satya

    2016-01-01

    Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive tumor with distant metastases being unusual. We present a case of metastatic DFSP treated with imatinib showing complete metabolic response to treatment. PMID:27385888

  20. Successful combination treatment of a patient with progressive juvenile localized scleroderma (morphea) using imatinib, corticosteroids, and methotrexate.

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    Inamo, Yasuji; Ochiai, Toyoko

    2013-01-01

    We report a case of progressive juvenile localized scleroderma (JLS or morphea) treated with a combination of imatinib, corticosteroids, and methotrexate. This therapy halted the progressive skin thickening and the hand and finger joint deformity in the early stages of the disease. We conclude that imatinib used in addition to standard treatment with systemic corticosteroids and methotrexate may be of therapeutic benefit for individuals with JLS.

  1. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors.

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    Cohen, Martin H; Farrell, Ann; Justice, Robert; Pazdur, Richard

    2009-02-01

    The purpose of the present application was to fulfill a postmarketing commitment to provide long-term efficacy and safety data on treatment with imatinib mesylate (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) in patients with CD117(+) unresectable and/or metastatic malignant gastrointestinal stromal tumors (GISTs). In addition, this application also provides evidence to support a change in the label to allow for an escalation of imatinib dosing to 800 mg/day for patients with progressive disease on a lower dose. Two open-label, controlled, multicenter, intergroup, international, randomized phase III studies were submitted -- one conducted by the European Organization for Research and Treatment of Cancer (n = 946) and the other by the Southwest Oncology Group (n = 746). These studies compared 400 mg/day of imatinib with 800 mg/day of imatinib. A combined analysis of the two studies was prospectively defined and agreed to by both groups. Both protocols allowed patients randomized to the 400-mg/day imatinib arm to cross over to 800 mg/day imatinib at progression. Objective responses were achieved in >50% of patients receiving either imatinib dose. The median progression-free survival time was approximately 20 months and the median overall survival (OS) time was approximately 49 months. In the combined analysis, 347 patients crossed over to 800 mg/day imatinib at the time of progression. The median OS time after crossover was 14.3 months. The most common adverse events (AEs) were fluid retention, nausea, fatigue, skin rash, gastrointestinal complaints, and myalgia. The most common laboratory abnormality was anemia. Most often the AEs were of mild-to-moderate severity. Fluid retention events and skin rash were numerically reported more often in the 800-mg/day treatment cohort of patients.

  2. Treatment of gastrointestinal stromal tumor with imatinib mesylate: a retrospective single-center experience in Heidelberg.

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    Kasper, Bernd; Kallinowski, Birgit; Herrmann, Thomas; Lehnert, Thomas; Mechtersheimer, Gunhild; Geer, Thomas; Ho, Anthony D; Egerer, Gerlinde

    2006-01-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Surgery has been the only effective therapy. However, many patients still eventually die of disease recurrence. Chemotherapy and radiation therapy have been of limited value. Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany. We summarized the data of 16 patients with advanced or metastatic GIST treated with imatinib mesylate in palliative and neoadjuvant settings. Overall response was 81%, with no evidence of disease (NED) in 3/16 (19%), partial response (PR) in 9/16 (56%) and stable disease (SD) in 1/16 (6%), whereas 3/16 patients (19%) suffered from progressive disease (PD). Mean follow-up was 18.6 months [range: 4-30]. Mean progression-free survival (PFS) was 17.6 months [range: 0-30], mean overall survival (OS) from initial diagnosis was 32.3 months [range: 5-122]. Most common side effects were periorbital edema and skin rash. Imatinib mesylate is well tolerated in a dose of up to 800 mg/day and has significant activity during long- term treatment of patients with advanced or metastatic GIST. Copyright 2006 S. Karger AG, Basel.

  3. The use of imatinib in the treatment of inoperable dermatofibrosarcoma protuberans in the area of the shoulder joint

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    Joanna Huszno

    2014-06-01

    Full Text Available Introduction. Dermatofibrosarcoma protuberans (DFSP is a rare sarcoma of the skin and subcutaneous tissue. The most common clinical problem is its local recurrence. The therapeutic procedure of choice is radical surgery. In the case of inoperable disease, targeted therapy with imatinib, a tyrosine kinase inhibitor, may cause significant reduction of tumor volume and even enable radical surgery. Objective. We present the effectiveness of imatinib for the treatment of unresectable DFSP localized in the area of the shoulder joint of a 62-year-old woman. Case report. The patient met the criteria for inclusion in treatment with imatinib. After 3 cycles of treatment, partial regression of the lesions (above 50% was observed. Therapy was complicated by hepatological side effects during the sixth cycle. Treatment was continued with a reduced dose when transaminase levels normalized. In a physical examination and imaging studies, further regression was observed. The patient has regained considerable mobility of the shoulder joint. A decision to continue the treatment has been made. Conclusions. The use of imatinib allowed a clinical benefit to be gained in the form of significant regression of lesions. A very good treatment response and significant improvement in quality of life of the patient were achieved. The patient has been treated with imatinib for 30 months.

  4. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury

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    Enming Joe Su

    2015-10-01

    Full Text Available Current therapies for Traumatic brain injury (TBI focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC within the brain can promote BBB permeability through PDGF receptor α (PDGFRα signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRα, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 minutes after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 hours, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC measurements, and with the preservation of cognitive function. Finally, analysis of CSF from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRα.

  5. Serum Natrium Determines Outcome of Treatment of Advanced GIST with Imatinib

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Rasmussen, Peter; Dybdahl, Helle;

    2011-01-01

    patients treated at the Department of Oncology, Aarhus University Hospital were retrospectively reviewed. Between 2001 and 2009, 80 patients with advanced GIST were treated with imatinib as first-line therapy. The median OS was 44 months (95% CI 31-56), and the 5-year OS was 40%. Since 2005, 32 patients......Treatment with tyrosine kinase inhibitors (TKIs) has drastically improved overall survival (OS) of patients with advanced GIST. The aim of this study is to evaluate the results of treatment with different TKIs on advanced GIST and identify prognostic factors for OS. The medical records of all...... were treated with sunitinib as 2nd-line therapy. The median time to progression was 9 months (95% CI: 3-13 months), and the 3-year OS was 30%. The data illustrate that data from large multicenter studies are reproducible in a single sarcoma centre. This retrospective study pointed to low serum sodium...

  6. Aurora kinase inhibitors: which role in the treatment of chronic myelogenous leukemia patients resistant to imatinib?

    Directory of Open Access Journals (Sweden)

    Giovanni Martinelli

    2009-02-01

    Full Text Available At present, there are no compounds in clinical development in the field of chronic myeloid leukemia (CML or Philadelphia-positive (Ph+ acute lymphoblastic leukemia (ALL that have been documented to harbor significant activity against the imatinib-resistant T315I mutation. Recent reports on the pre-clinical activity of some emerging tyrosine kinase inhibitors such as ON012380, VX-680 and PHA-739358 promise possible clinical efficacy against this specific Bcr-Abl mutant form. Here, we focus on the role of aurora kinase inhibitor VX-680 and PHA-739358 in blocking the leukemogenic pathways driven by wild-type and T315I-Bcr-Abl in CML or Ph+ ALL by reviewing recent research evidence. We also discuss the possibility of employing aurora kinase inhibitors as a promising new therapeutic approach in the treatment of CML and Ph+ ALL patients resistant to first and second generation TK inhibitors.

  7. Uso neoadjuvante do mesilato de imatinibe no tratamento de GIST retal volumoso: relato de caso Neoadjuvant use of imatinib mesylate for treatment of large rectal GIST: case report

    Directory of Open Access Journals (Sweden)

    Paulo Rocha França Neto

    2011-03-01

    Full Text Available Tem sido relevante o papel das drogas que interferem na atividade tirosina-quinase dos receptores c-kit, no tratamento dos tumores derivados do estroma gastrintestinal (GISTs, sobretudo em tumores volumosos. Relata-se o caso de um paciente do sexo masculino, 56 anos, obeso, com quadro de peso retoanal associado a tenesmo e à sensação de evacuação incompleta. Foi diagnosticado volumoso GIST de reto inferior de localização posterior, visualizado por ressonância magnética e confirmado por estudo imunoistoquímico em punção-biópsia parassacral, guiada por tomografia. A impressão inicial foi de necessidade de amputação abdômino-perineal do reto, pois havia importante compressão do canal anal e do aparelho esfincteriano. Optou-se, então, por indicação de neoadjuvância com mesilato de imatinibe (Glivec® na tentativa de preservação esfincteriana. Após quatro meses de tratamento, apresentava, ao toque retal, redução significativa (cerca de 50% do volume da massa e em menor grau à ressonância magnética. Paciente foi submetido à excisão total do mesorreto e anastomose colo-anal manual, com ileostomia protetora. Evoluiu com necrose do cólon abaixado, tendo sido realizada ressecção do mesmo e colostomia terminal ilíaca. O paciente recusou a se submeter a uma nova tentativa de abaixamento colo-anal, tendo sido fechada a ileostomia e restabelecido trânsito pela colostomia ilíaca. No tratamento dos GISTs de reto muito volumosos ou irressecáveis, deve-se avaliar a indicação pré-operatória do imatinibe, uma vez que a cirurgia radical deve ser sempre indicada, a fim de minimizar a possibilidade de recorrência local.The role of drugs that intervene with the tirosine kinase activity on the c-kit receptors in the treatment of gastrointestinal stromal tumors (GISTs has been considered very important, mainly in large tumors. We report a case of a male patient, 56 years-old, obese, presenting with feeling of rectal pressure

  8. Maternal, Fetal, and Neonatal Imatinib Levels With Treatment of Chronic Myeloid Leukemia in Pregnancy.

    Science.gov (United States)

    Burwick, Richard M; Kuo, Kelly; Brewer, Diana; Druker, Brian J

    2017-05-01

    Pregnant women with chronic myeloid leukemia (CML) can be treated effectively with the tyrosine-kinase inhibitor imatinib, but data regarding fetal and neonatal exposure and safety are limited. We present a patient with newly diagnosed CML in early pregnancy. Leukapheresis and interferon-α were initiated in the second trimester with limited benefit. Imatinib was subsequently started at 28 weeks of gestation with complete hematologic response within 4 weeks. No significant maternal or neonatal adverse effects were noted, but imatinib and its primary active metabolite concentrated in maternal breast milk and neonatal urine. Imatinib is effective for CML in pregnancy, but caution is warranted in light of potentially unrecognized fetal and neonatal effects.

  9. Dasatinib treatment can overcome imatinib and nilotinib resistance in CML patient carrying F359I mutation of BCR-ABL oncogene.

    Science.gov (United States)

    Barańska, Marta; Lewandowski, Krzysztof; Gniot, Michał; Iwoła, Małgorzata; Lewandowska, Maria; Komarnicki, Mieczysław

    2008-01-01

    Point mutations of bcr-abl tyrosine kinase are the most frequent causes of imatinib resistance in chronic myeloid leukaemia (CML) patients. In most CML cases with BCR-ABL mutations leading to imatinib resistance the second generation of tyrosine kinase inhibitors (TKI- e.g. nilotinib or dasatinib) may be effective. Here, we report a case of a CML patient who during imatinib treatment did not obtain clinical and cytogenetic response within 12 months of therapy. The sequencing of BCR-ABL kinase domains was performed and revealed the presence of a F359I point mutation (TTC-to-ATC nucleotide change leading to Phe-to-Ile amino acid substitution). After 1 month of nilotinib therapy a rapid progression of clinical symptoms was observed. In the presence of the F359I point mutation only dasatinib treatment overcame imatinib and nilotinib resistance.

  10. Expression of c-kit receptor in human cholangiocarcinoma and in vivo treatment with imatinib mesilate in chimeric mice

    Institute of Scientific and Technical Information of China (English)

    Thomas Kamenz; Karel Caca; Thilo Blüthner; Andrea Tannapfel; Joachim M(o)ssner; Marcus Wiedmann

    2006-01-01

    AIM: To investigate the c-kit expression in biliary tract cancer cell lines and histological sections from patients with extrahepatic cholangiocarcinoma (CC) and to evaluate the efficacy of in vitro and in vitro treatment with imatinib mesilate.METHODS: The protein expression of c-kit in the human biliary tract cancer cell lines Mz-ChA-2 and EGI-1 and histological sections from 19 patients with extrahepatic CC was assessed by immunoblotting,immunocytochemistry, and immunohistochemistry. The anti-proliferative effect of imatinib mesilate on biliary tract cancer cell lines Mz-ChA-2 and EGI-1 was studied in vitro by automated cell counting. In addition, immunodeficient NMRI mice (TaconicTM) were subcutaneously injected with 5×106 cells of cell lines MzChA-2 and EGI-1. After having reached a tumour volume of 200 mm3, daily treatment was started intraperitoneally with imatinib mesilate at a dose of 50 mg/kg or normal saline (NS).Tumor volume was calculated with a Vernier caliper.After 14 d, mice were sacrificed with tumors excised and tumor mass determined.RESULTS: Immunoblotting revealed presence of c-kit in Mz-ChA-2 and absence in EGI-1 cells.Immunocytochemistry with c-kit antibodies displayed a cytoplasmatic and membraneous localization of receptor protein in Mz-ChA-2 cells and absence of c-kit in EGI-1 cells, c-kit was expressed in 7 of 19 (37%) extrahepatic humanCC tissue samples, 2 showed a moderate and 5 a rather weak immunostaining. Imatinib mesilate at a low concentration of 5 μmol/L caused a significant growth inhibition in the c-kit positive cell line Mz-ChA-2 (31%), but not in the c-kit negative cell line EGI-1 (0%) (P< 0.05). Imatinib mesilate at an intermediate concentration of 10 μmol/L inhibited cellular growth of both cell lines (51% vs 57%). Imatinib mesilate at a higher concentration of 20 μmol/L seemed to have a general toxic effect on both cell lines. The IC50 values were 9.7 μmol/L and 11 μmol/L, respectively. After 14 d of in vitro

  11. Determination of serum levels of imatinib mesylate in patients with chronic myeloid leukemia: validation and application of a new analytical method to monitor treatment compliance.

    Science.gov (United States)

    Rezende, Vinícius Marcondes; Rivellis, Ariane Julio; Gomes, Melissa Medrano; Dörr, Felipe Augusto; Novaes, Mafalda Megumi Yoshinaga; Nardinelli, Luciana; Costa, Ariel Lais de Lima; Chamone, Dalton de Alencar Fisher; Bendit, Israel

    2013-01-01

    The goal of this study was to monitor imatinib mesylate therapeutically in the Tumor Biology Laboratory, Department of Hematology and Hemotherapy, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP). A simple and sensitive method to quantify imatinib and its metabolite (CGP74588) in human serum was developed and fully validated in order to monitor treatment compliance. The method used to quantify these compounds in serum included protein precipitation extraction followed by instrumental analysis using high performance liquid chromatography coupled with mass spectrometry. The method was validated for several parameters, including selectivity, precision, accuracy, recovery and linearity. The parameters evaluated during the validation stage exhibited satisfactory results based on the Food and Drug Administration and the Brazilian Health Surveillance Agency (ANVISA) guidelines for validating bioanalytical methods. These parameters also showed a linear correlation greater than 0.99 for the concentration range between 0.500 µg/mL and 10.0 µg/mL and a total analysis time of 13 minutes per sample. This study includes results (imatinib serum concentrations) for 308 samples from patients being treated with imatinib mesylate. The method developed in this study was successfully validated and is being efficiently used to measure imatinib concentrations in samples from chronic myeloid leukemia patients to check treatment compliance. The imatinib serum levels of patients achieving a major molecular response were significantly higher than those of patients who did not achieve this result. These results are thus consistent with published reports concerning other populations.

  12. SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation

    Directory of Open Access Journals (Sweden)

    Giallongo Cesarina

    2013-02-01

    Full Text Available Abstract Background SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC. Methods We evaluated SPARC expression using real-time PCR and western blotting. SPARC serum levels were detected by ELISA assay. Finally we analyzed the interaction between exogenous SPARC and imatinib (IM, in vitro, using ATP-lite and cell cycle analysis. Results Our study shows that the CML cells of patients at diagnosis have a low mRNA and protein expression of SPARC. Low serum levels of this protein are also recorded in CML patients at diagnosis. However, after IM treatment we observed an increase of SPARC mRNA, protein, and serum level in the peripheral blood of these patients that had already started at 3 months and was maintained for at least the 18 months of observation. This SPARC increase was predominantly due to monocyte production. In addition, exogenous SPARC protein reduced the growth of K562 cell line and synergized in vitro with IM by inhibiting cell cycle progression from G1 to S phase. Conclusion Our results suggest that low endogenous SPARC expression is a constant feature of BCR/ABL positive cells and that IM treatment induces SPARC overproduction by normal cells. This exogenous SPARC may inhibit CML cell proliferation and may synergize with IM activity against CML.

  13. Advanced gastrointestinal stromal tumor patients with complete response after treatment with imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    Kun-Chun Chiang; Tsung-Wen Chen; Chun-Nan Yeh; Feng-Yuan Liu; Hsiang-Lin Lee; Yi-Yin Jan

    2006-01-01

    AIM: Most gastrointestinal stromal tumors (GISTs)express constitutively activated mutant isoforms of kit kinase or platelet-derived growth factor receptor alpha (PDGFRA), which are potential therapeutic targets for imatinib mesylate (Glivec). Partial response occurred in almost two thirds of GIST patients treated with Glivec.However, complete response (CR) after Glivec therapy was sporadically reported. Here we illustrated advanced GIST patients with CR after Glivec treatment.METHODS: Between January 2001 and June 2005,42 advanced GIST patients were treated with Glivec.Patients were administered 400 mg of Glivec in 100-mg capsules, taken orally daily with food. The response of the tumor to Glivec was evaluated after one month, three months, and every three months thereafter or whenever medical need was indicated. Each tumor of patients was investigated for mutations of kit or PDGFRA.RESULTS: The median follow-up time of the 42 ad-vanced GIST patients treated with Glivec was 16.9 months (range, 1.0- 47.0 months). Overall, 3patients had complete response CR (7.1%), 26 partial response (67.8%), 5 stationary disease (11.9%), and 3 progressive disease (11.9%). The median duration of Glivec administration for the three patients was 36months (range, 23-36 months). The median time to CR after Glivec treatment was 20 months (range, 9-26months). Deletion and insertion mutations of c-kit exon 11 and insertion mutation of c-kit exon 9 were found in two cases and one case, respectively.CONCLUSION: Complete response (CR) can be achieyed in selected advanced GIST patients treated with Glivec. The median time to CR after Glivec treatment was 20 months. Deletion and insertion mutations of kit exon 11 and insertion mutation of kit exon 9 contribute to the genetic features in these selected cases.

  14. Sunitinib for Taiwanese patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance

    Institute of Scientific and Technical Information of China (English)

    Yen-Yang Chen; Chun-Nan Yeh; Chi-Tung Cheng; Tsung-Wen Chen; Kun-Ming Rau; Yi-Yin Jan; Miin-Fu Chen

    2011-01-01

    AIM: To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwanese gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure. METHODS: Between 2001 and May 2010, 199 Taiwanese patients with metastatic GIST were treated at Chang Gung Memorial Hospital. Among them, 23 (11.6%) patients receiving sunitinib were investigated. RESULTS: Sixteen male and 7 female patients with a median age of 59 years (range: 24-83 years) received sunitinib. Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance. The median duration of sunitinib administration was 6.0 mo (range: 2-29 mo). The clinical benefit was 65.2% [2 complete response (CR), 4 partial response (PR), and 9 stationary disease (SD); 15/23]. In 12 patients harboring mutations of the kit gene at exon 11, the clinical benefit rate (CR, PR, and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant, P = 0.344). The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type, KIT exon 9, or KIT exon 11 mutations. Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%), followed by anemia (17.4%), and neutropenia (13.0%). During the median 7.5-mo follow-up after sunitinib use, the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo, respectively. CONCLUSION: Sunitinib appears to be an effective treatment for Taiwanese with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwanese advanced GIST patients.

  15. Chronic Myeloid Leukemia with Variant Chromosomal Translocations: Results of Treatment with Imatinib Mesylate

    Directory of Open Access Journals (Sweden)

    Rohan Bhise

    2013-01-01

    Full Text Available Objective: To evaluate the efficacy of imatinib in chronic myeloid leukemia patients with variant translocations. Methods: Forty eight chronic myeloid leukemia patients carrying variant translocations and treated with imatinib at our institute were considered for the study. Survival and response rates were evaluated. Results: The median follow up was 48 months(m. Forty three (89.58% patients achieved complete hematologic response. Thirty one (64.58% patients achieved complete cytogenetic response and 19(39.58% achieved major molecular response anytime during their follow up period. Only 18.75% of the patients achieved complete cytogenetic response and major molecular response within the stipulated time frames.The estimated overall survival at 48 m median follow up was 81.2%.The progression free survival was also 81.2% and the event free survival was 79.1%.There was no significant survival difference between low vs intermediate and high risk sokal group. Conclusion: We report suboptimal responses to imatinib in chronic myeloid leukemia with variant translocations. Further studies with imatinib and the newer more active drugs dasatinib and nilotinib are justified.

  16. Time-series analysis in imatinib-resistant chronic myeloid leukemia K562-cells under different drug treatments.

    Science.gov (United States)

    Zhao, Yan-Hong; Zhang, Xue-Fang; Zhao, Yan-Qiu; Bai, Fan; Qin, Fan; Sun, Jing; Dong, Ying

    2017-08-01

    Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein. Imatinib is the first-line treatment of CML; however, many patients are resistant to this drug. In this study, we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments. GSE24946 was downloaded from the GEO database, which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5). Three drug treatment groups were considered for this study: arsenic trioxide (ATO), AMN107, and ATO+AMN107. Each group had one sample at each time point (3, 12, 24, and 48 h). Time-series genes with a ratio of standard deviation/average (coefficient of variation) >0.15 were screened, and their expression patterns were revealed based on Short Time-series Expression Miner (STEM). Then, the functional enrichment analysis of time-series genes in each group was performed using DAVID, and the genes enriched in the top ten functional categories were extracted to detect their expression patterns. Different time-series genes were identified in the three groups, and most of them were enriched in the ribosome and oxidative phosphorylation pathways. Time-series genes in the three treatment groups had different expression patterns and functions. Time-series genes in the ATO group (e.g. CCNA2 and DAB2) were significantly associated with cell adhesion, those in the AMN107 group were related to cellular carbohydrate metabolic process, while those in the ATO+AMN107 group (e.g. AP2M1) were significantly related to cell proliferation and antigen processing. In imatinib-resistant CML cells, ATO could influence genes related to cell adhesion, AMN107 might affect genes involved in cellular carbohydrate metabolism, and the combination therapy might regulate genes involved in cell proliferation.

  17. Imatinib treatment causes substantial transcriptional changes in adult Schistosoma mansoni in vitro exhibiting pleiotropic effects.

    Directory of Open Access Journals (Sweden)

    Christin Buro

    2014-06-01

    Full Text Available BACKGROUND: Schistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec. Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites. METHODOLOGY/PRINCIPAL FINDINGS: Here we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common

  18. Leucemia Mielóide Crônica: causas de falha do tratamento com mesilato de imatinibe Chronic Myeloid Leukemia: causes of treatment failure with imatinib

    OpenAIRE

    Katia B.B. Pagnano

    2008-01-01

    O mesilato de imatinibe (MI) é atualmente o tratamento de escolha da Leucemoa Mielóide Crônica (LMC), mas, apesar dos excelentes resultados, não é capaz de erradicar completamente a doença, podendo ocorrer resistência ao tratamento. O mecanismo mais conhecido de resistência é o desenvolvimento de mutações do BCR-ABL, que impedem a ação ligação adequada do imatinibe à quinase, além de amplificação gênica e evolução clonal. No entanto, há uma série de outros mecanismos envolvidos e ainda pouco ...

  19. [Resection of a Huge Gastrointestinal Stromal Tumor of the Stomach Following Neoadjuvant Chemotherapy with Imatinib].

    Science.gov (United States)

    Sato, Yoshihiro; Karasawa, Hideaki; Aoki, Takeshi; Imoto, Hirofumi; Tanaka, Naoki; Watanabe, Kazuhiro; Abe, Tomoya; Nagao, Munenori; Ohnuma, Shinobu; Musha, Hiroaki; Takahashi, Masanobu; Motoi, Fuyuhiko; Naitoh, Takeshi; Ishioka, Chikashi; Unno, Michiaki

    2016-11-01

    We report a case of a huge gastric gastrointestinal stromal tumor(GIST)that was safely resected followingpreoperative imatinib therapy. A 72-year-old woman was hospitalized with severe abdominal distension. Computed tomography revealed a 27×17 cm tumor in the left upper abdominal cavity. The patient was diagnosed with high risk GIST by EUS-FNA. We initiated preoperative adjuvant chemotherapy with imatinib to achieve a reduction of operative risks and functional preservation. After 6 months of chemotherapy, CT showed a reduction in the tumor size and the patient underwent partial gastrectomy and partial resection of the diaphragm. Histologically, most of the tumor cells were replaced by hyalinized collagen and viable cells were scattered only around the blood vessels. Neoadjuvant chemotherapy with imatinib has the potential to become an important therapeutic option for the treatment of huge GISTs.

  20. Pheochromocytoma : a review on preoperative treatment with phenoxybenzamine or doxazosin

    NARCIS (Netherlands)

    van der Zee, P A; de Boer, A|info:eu-repo/dai/nl/075097346

    2014-01-01

    BACKGROUND: During surgical treatment of pheochromocytoma,`haemodynamic instability may occur. To prevent this, patients receive preoperative treatment with an alpha-blocker. Nowadays, some centres use phenoxybenzamine, while others use doxazosin. The purpose of this review is to analyse the current

  1. Determination of serum levels of imatinib mesylate in patients with chronic myeloid leukemia: validation and application of a new analytical method to monitor treatment compliance

    Directory of Open Access Journals (Sweden)

    Vinícius Marcondes Rezende

    2013-01-01

    Full Text Available OBJECTIVE: The goal of this study was to monitor imatinib mesylate therapeutically in the Tumor Biology Laboratory, Department of Hematology and Hemotherapy, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP. A simple and sensitive method to quantify imatinib and its metabolite (CGP74588 in human serum was developed and fully validated in order to monitor treatment compliance. METHODS: The method used to quantify these compounds in serum included protein precipitation extraction followed by instrumental analysis using high performance liquid chromatography coupled with mass spectrometry. The method was validated for several parameters, including selectivity, precision, accuracy, recovery and linearity. RESULTS: The parameters evaluated during the validation stage exhibited satisfactory results based on the Food and Drug Administration and the Brazilian Health Surveillance Agency (ANVISA guidelines for validating bioanalytical methods. These parameters also showed a linear correlation greater than 0.99 for the concentration range between 0.500 µg/mL and 10.0 µg/mL and a total analysis time of 13 minutes per sample. This study includes results (imatinib serum concentrations for 308 samples from patients being treated with imatinib mesylate. CONCLUSION: The method developed in this study was successfully validated and is being efficiently used to measure imatinib concentrations in samples from chronic myeloid leukemia patients to check treatment compliance. The imatinib serum levels of patients achieving a major molecular response were significantly higher than those of patients who did not achieve this result. These results are thus consistent with published reports concerning other populations.

  2. Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    Seiji Suzuki; Shotaro Maeda; Takashi Tajiri; Koji Sasajima; Masayuki Miyamoto; Hidehiro Watanabe; Tadashi Yokoyama; Hiroshi Maruyama; Takeshi Matsutani; Aimin Liu; Masaru Hosone

    2008-01-01

    A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor (GIST). Computed tomography (CT) and magnetic resonance imaging (MRI) 107 mo after the operation, revealed a cystic mass (14 cm in diameter) and a solid mass (9 cm in diameter) in the right and left lobes of the liver, respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate (IM) treatment, 400mg/day orally. Following the IM treatment for a period of 35 mo, the patient underwent partial hepatectomy (S4+S5). The effect of IM on the metastatic lesions was interpreted as pathologic complete response (CR). Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

  3. The in-vitro antiproliferative effect of PRI-2191 and imatinib applied in combined treatment with cisplatin, idarubicin, or docetaxel on human leukemia cells.

    Science.gov (United States)

    Switalska, Marta; Nasulewicz-Goldeman, Anna; Opolska, Aleksandra; Maciejewska, Magdalena; Kutner, Andrzej; Wietrzyk, Joanna

    2012-01-01

    Imatinib mesylate (Gleevec, STI571) is a specific inhibitor of the Bcr/Abl fusion tyrosine kinase that exhibits potent antileukemic effects in chronic myelogenous leukemia. Bcr/Abl-positive K562 and Bcr/Abl-negative HL-60 human leukemia cells were used to investigate the effect of PRI-2191, a calcitriol analog, on the biological effects of imatinib combined with other anticancer drugs. The results show that PRI-2191 enhances the antiproliferative effect of imatinib on HL-60 cells. When these two agents together are applied with either docetaxel or cisplatin, but not with idarubicin, the antiproliferative effect could still be enhanced. Moreover, when the interaction between the chemotherapy agents was antagonistic or additive, PRI-2191 could even shift it to synergism. This effect correlated with an accumulation of HL-60 cells in the G0/G1 phase of the cell cycle and a decrease in the percentage of cells in the G2/M and S stage in the ternary combinations used. PRI-2191 did not influence apoptosis induced by imatinib alone or in ternary combinations with all the chemotherapy agents used. These results may suggest that the stronger antiproliferative effect of the combined treatment with PRI-2191 on HL-60 cells is related to cell cycle arrest rather than to the induction of apoptosis.

  4. Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis.

    Science.gov (United States)

    Hasselbalch, Hans Carl; Bjerrum, Ole Weiss; Jensen, Bjarne Anker; Clausen, Nielsaage Tøffner; Hansen, Per Boye; Birgens, Henrik; Therkildsen, Marianne Hamilton; Ralfkiaer, Elisabeth

    2003-12-01

    Imatinib mesylate targets the adenosine triphosphate (ATP)-binding sites of the protein tyrosine kinase domains associated with Bcr-abl, the platelet-derived growth factor (PDGF) and c-kit. In idiopathic myelofibrosis (IMF) PDGF is considered to be one of the growth factors responsible for the development of bone marrow fibrosis. Recently, it has been shown that imatinib has antifibrogenic effect on bone marrow fibrosis in chronic myelogenous leukemia. Treatment with imatinib alone in IMF has been associated with significant side effects. In this study, the safety and efficacy of imatinib therapy in IMF, either administered as a single agent or in combination with hydroxyurea (HU) and/or alpha-interferon (IFN-alpha) are evaluated. Eleven patients (median age, 63 years; range, 33-82 years) with IMF (n = 8) or postpolycythemic myelofibrosis (PPMF) (n = 3) were studied All patients had been treated with HU (n = 9) and/or IFN (n = 7) before study entry. In all but one patient, treatment with these agents was discontinued when imatinib therapy was instituted. One patient continued IFN when treatment with imatinib was started. Imatinib was given at a dose of 400 mg/day. Nine patients were in an advanced disease phase. The patients have been followed for a median period of 2 months (range, 0.5-12 months). Treatment with imatinib has been stopped in six patients (55%), because of overt side effects (n = 4), recurrence of transitory dizziness and visual defects owing to a rising platelet count (n = 1), or the occurrence of an acute subdural hemorrhage that was evacuated without neurological deficits (n = 1). In nine patients imatinib treatment was followed by a rise in leukocyte and platelet counts that required combination with HU or IFN. The combined treatment modalities were followed by a rapid decrease in cell counts and were well tolerated apart from IFN side effects. A beneficial effect of imatinib was documented in three patients. It is concluded that leukocytosis

  5. Clinicopathological studies on three preoperative combined treatments for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Yuji; Ichikawa, Daisuke; Iizuka, Ryouji; Hagiwara, Akeo; Sawai, Kiyoshi; Yamaguchi, Toshiharu; Takahashi, Toshio [Kyoto Prefectural Univ. of Medicine (Japan)

    1995-09-01

    To prevent postoperative local recurrence of rectal cancer, we treated patients using preoperative hyperthermia (5-6 times), irradiation (total 30 Gy) and 5-fluorouracil suppository (2,000-2,500 mg). The subjects were 31 patients given combined treatments and 28 patients given surgery alone. The results were as follows: Histologically, therapeutic effects were recognized in 80.6% of patients receiving combined treatments. The mean distance from the adventitia to the site of cancer infiltration was 6.54 mm in the combined treatments group and 3.35 mm in the surgery alone group. The difference between the two was significant (p<0.05). The rate of local recurrence in the combined treatments group was less than that in the surgery alone group. No systemic side effects nor severe complications were observed during hospitalization in the combined treatments group. The survival rate of the combined treatments group was higher than that of the surgery alone group. It was considered that combined preoperative treatments for rectal cancer were beneficial to survival and local control. (author).

  6. Long-term safety and efficacy of dasatinib in the treatment of chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib

    Directory of Open Access Journals (Sweden)

    Shoumariyeh K

    2014-09-01

    Full Text Available Khalid Shoumariyeh, Nikolas von BubnoffDepartment of Hematology, Oncology and Stem Cell Transplantation, University Hospital Freiburg, Freiburg, Germany Abstract: Treatment of chronic myeloid leukemia (CML has undergone dramatic changes in the last decade. Dissecting the molecular pathways that lead to the development of this disease resulted in the development of targeted therapy against the molecular driver of CML, namely the aberrantly activated tyrosine kinase BCR-ABL1. By introducing the tyrosine kinase inhibitor imatinib to the treatment repertoire, the natural course of the disease has been dramatically altered and overall survival of patients with CML prolonged substantially. Nevertheless, a significant number of patients are primarily resistant, acquire resistance during the course of their disease, or do not tolerate the intake of imatinib due to adverse effects. Second-generation tyrosine kinase inhibitors were developed in an attempt to overcome these problems. Dasatinib is a potent oral kinase inhibitor that was originally developed as an Src-kinase inhibitor but exhibited promising potency against BCR-ABL1 as well. Phase I and II trials demonstrated efficacy in patients failing imatinib, and thus dasatanib was approved in 2006 for the treatment of imatinib-resistant or -intolerant patients with chronic-phase CML harboring the BCR-ABL1 fusion protein. It has since shown promising efficacy and good overall tolerability in subsequent clinical trials, including the Phase III first-line DASISION trial that led to the extension of its approval for first-line treatment of chronic-phase CML. The following review summarizes the available data on the long-term efficacy and safety of dasatinib as a second-line therapy in chronic-phase CML. Keywords: BCR-ABL1, TKI, CML-CP, second-line treatment

  7. Adherence to treatment with imatinib in chronic myeloid leukemia: a study of the first decade of responses obtained at a Brazilian hospital

    Directory of Open Access Journals (Sweden)

    Samuel Roosevelt Campos dos Reis

    2013-06-01

    Full Text Available Objetive: The aim of this study was to identify the reasons for failure in adherence to imatinib mesylate treatment in chronic myeloid leukemia. Methods: A retrospective review was performed of 100 non-electronic records of patients with Ph+ chronic myeloid leukemia treated with imatinib mesylate. The study period was from January 2001 to January2011. Data were analyzed by Chi-Square and Correspondence analysis using the Statistical Analysis System software package. Results: At the beginning of treatment 41% of patients were in advanced stages of the disease. The unavailability of the drug (44.8% and myelotoxicity (25.7% were the most frequent reasons for interruption. The adherence rate was 95% induced complete cytogenetic response, major cytogenetic response and major molecular response. Conclusion: The population of this study obtained lower-than-expected therapeutic responses compared to other studies.

  8. Preoperative Assessment of Different Treatment Modalities in Bronchial Asthma Patients

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    Kawther A. Azzam M.D. and **Sahar S. Khattab MD

    2003-06-01

    Full Text Available This study was performed to assess the effectiveness of acupuncture and medical therapies of bronchial asthma preoperatively. Sixty patients suffered from mild to moderate bronchial asthma and coming for elective operations were chozen from the outpatient clinic of Al-Zahraa University Hospital. Patients were randomly divided into three equal groups (n=20 each. Group I patients (drug group received oral theophylline and Salbutamol (ventolin inhaler according to the needs. Group II patients (drug +ear acupuncture group received same medical treatment as in group I and added ear acupuncture. Group III patients (drug + ear and body acupuncture group received same medical treatment as in group I and II and added ear and body acupuncture. Ventilatory function tests through spirometer and interleukin-13 estimation were performed before treatment and after two weeks of treatment. Improvement of subjective and objective parameters had occurred with significant decrease in the mean serum level of interleukin-13 and decrease in the mean number of using b-agonist puffs after two weeks of treatment in the three groups, with the best results being in group III than in group II and then in group I. Conclusion: Interleukin-13 estimation togheter with ventilatory function tests is a useful parameter for pre-operative assessment and evaluation of asthmatic patients. Also medication was significantly reduced when combined with acupuncture.

  9. Prospect of Imatinib in the Treatment of Systemic Sclerosis%伊马替尼在系统性硬化症的应用前景

    Institute of Scientific and Technical Information of China (English)

    刘心娟; 李梦涛; 曾小峰

    2011-01-01

    系统性硬化症(systemic sclerosis,SSc)以胶原过度产生和细胞外基质过度沉积导致组织纤维化为主要特征.血小板源性生长因子受体(platelet-derived growth factor receptor,PDGFR)、转化生长因子-β(transforming growth factor-β,TGF-β)以及细胞免疫的异常可能参与了这一过程.甲磺酸伊马替尼(imatinib mesylate,IM)是一种人工合成的酪氨酸蛋白激酶抑制剂,最早被用于治疗慢性粒细胞白血病,近年发现其具有抗纤维化作用.目前认为,IM可以通过抑制PDGFR和TGF-β,并可能通过影响调节性T细胞的增殖和功能达到治疗SSc的目的.但是,IM治疗SSc的临床研究刚刚起步,其疗效及安全性有待已经启动的大规模随机对照临床试验(RCT)的结果来评价.%Systemic sclerosis is a multisystem fibrotic disorder characterized by excessive deposition of collagen and other extracellular matrix components. The disorders of platelet-derived growth factor receptor (PDGFR),transforming growth factor-β (TGF-β) and cell-mediated immunity are hypothesized to be involved in the pathogenesis of systemic sclerosis (SSc). Imatinib mesylate is a small molecule that antagonizes specific tyrosine kinases which has been approved to be the treatment of chronic myeloid leukemia. Recently,imatinib began to be used to treat SSc which is mostly based on the known anti-proliferative properties, as an inhibitor of PDGFR and TGF-β, even anti-regulatory T lymphocytes (Treg). The preliminary clinical data raised the possibility that patients with SSc may benefit clinically from imatinib therapy. Large prospective randomized clinical trials are needed to further investigate the effects of imatinib on SSc.Gratifyingly, several clinical trials using imatinib in SSc are currently in progress.

  10. Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: Implications of imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    Chun-Nan Yeh; Tsung-Wen Chen; Ting-Jung Wu; Swei Hsueh; Yi-Yin Jan

    2006-01-01

    AIM: To examine the impact of imatinib mesylate (Glivec)on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status.METHODS: Thirty-three of 74 (44.6%) small bowel gastrointestinal stromal tumor (GIST) patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients.Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients.Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha (PDGFRA). The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed.RESULTS: Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response (PR) (67.8%). Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate (PR) was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate (ORR) of 66.7% (not significant).CONCLUSION: Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients with advanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs.There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.

  11. Effective Downsizing of a Large Oesophageal Gastrointestinal Stromal Tumour with Neoadjuvant Imatinib Enabling an Uncomplicated and without Tumour Rupture Laparoscopic-Assisted Ivor-Lewis Oesophagectomy.

    Science.gov (United States)

    Neofytou, Kyriakos; Costa Neves, Mafalda; Giakoustidis, Alexandros; Benson, Charlotte; Mudan, Satvinder

    2015-01-01

    Neoadjuvant imatinib for gastrointestinal stromal tumours (GISTs) is increasingly used nowadays. As oesophagectomy is associated with high morbidity and mortality, a preoperative downsizing of an oesophageal GIST to limit the extent of resection would be ideal. Because these tumours are rare and neoadjuvant treatment with imatinib is recent, there is limited literature available regarding neoadjuvant administration of imatinib in patients with oesophageal GISTs. A 50-year-old woman presented with total dysphagia. An upper endoscopy and biopsy revealed a large submucosal KIT-positive GIST obstructing the mid oesophagus. CT confirmed a lesion measuring 99 mm × 50 mm × 104 mm. Because the size and location of the tumour increased the risk of intraoperative rupture, it was decided to administer preoperative imatinib. The patient had an excellent clinical and radiological response. Her dysphagia gradually resolved and the follow-up CT scans of the first 10 months showed a gradually reducing tumour size to 54 mm × 33 mm × 42 mm. The patient underwent an uneventful laparoscopic-assisted Ivor-Lewis oesophagectomy. Postoperatively, the patient continued with adjuvant imatinib. At the last follow-up, 1 year from operation and 38 months from the diagnosis, the patient is disease free.

  12. [Literature review and presentation of our own research results regarding the effects on bone of tyrosine kinase inhibitors imatinib and nilotinib used in the treatment of oncohematological diseases].

    Science.gov (United States)

    Kirschner, Gyöngyi; Balla, Bernadett; Kósa, János; Horváth, Péter; Kövesdi, Andrea; Lakatos, Gergely; Takács, István; Nagy, Zsolt; Tóbiás, Bálint; Árvai, Kristóf; Lakatos, Péter

    2016-09-01

    Tyrosine kinase inhibitors are widely used for treatment of certain oncohematological diseases. Several clinical studies have confirmed that specific BCR-ABL tyrosine kinase inhibitors alter the physiological process of bone tissue in a complex and unclearly identified manner. Since these treatments are being given to more and more patients, and the therapy takes decades or lasts even lifelong, it is justifiable to obtain more detailed knowledge of the molecular background of these mechanisms. In this article the authors summarize preliminary research results and human clinical observations on imatinib and nilotinib which are related to bone metabolism, and present the results of their own experiments in in vitro osteoblast cultures. Based on the presented results, the effects of imatinib and nilotinib on bone cells depend on the concentration of imatinib and nilotinib, the maturation stage of the cells and the distribution ratio of receptor tyrosine kinase signaling pathways. In this study the authors firstly prepared a stop-gap, comprehensive review in the Hungarian literature, regarding the effects of tyrosine kinase inhibitors on bone metabolism. In addition they firstly performed whole transcriptome analysis on osteoblasts in order to obtain a better understanding of the cellular molecular mechanisms. Orv. Hetil., 2016, 157(36), 1429-1437.

  13. Imatinib treatment induces CD5+ B lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia.

    Directory of Open Access Journals (Sweden)

    Silvia Catellani

    Full Text Available Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32, the percentage of bone marrow CD20(+CD5(+sIgM(+ lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and -7. All patients with high number of CD20(+CD5(+sIgM(+ cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20(+CD5(+sIgM(+ lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20(+CD5(+sIgM(+ cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response.

  14. Positron Emission Tomography as a Surrogate Marker for Evaluation of Treatment Response in Patients with Desmoid Tumors under Therapy with Imatinib

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    Bernd Kasper

    2013-01-01

    Full Text Available We used 2-deoxy-2-[18F] fluoro-D-glucose (FDG positron emission tomography (PET to evaluate patients with desmoid tumors undergoing therapy with imatinib. The study included 22 patients with progressive disease (PD of a biopsy proven desmoid tumor treated orally with imatinib 800 mg daily. Patients were examined using PET prior to onset of therapy and during treatment. Restaging was performed in parallel using computed tomography (CT and/or magnetic resonance imaging (MRI. Outcome of 22 evaluable patients was as follows: five patients with partial response (PR; twelve patients with stable disease (SD accounting for 77% with non-progressive disease; five patients showed PD. A 30% decrease of the mean average standardized uptake value (SUV of sequential PET examinations could be demonstrated; no patient demonstrated a substantial increase in SUV. Patients with PR/SD were matched to a group of nonprogressive disease and tested versus PD. The initial average SUV and seem to be candidates for a response prediction with an approximate -value of 0.06553 and 0.07785, respectively. This is the first larger series of desmoid patients monitored using PET showing that early SUV changes may help to discriminate responders from nonresponders and, thus, to decide whether imatinib therapy should be continued.

  15. Is Adherence to Imatinib Mesylate Treatment Among Patients with Chronic Myeloid Leukemia Associated with Better Clinical Outcomes in Qatar?

    Science.gov (United States)

    Al-Dewik, Nader I.; Morsi, Hisham M.; Samara, Muthanna M.; Ghasoub, Rola S.; Gnanam, Cinquea C.; Bhaskaran, Subi K.; Nashwan, Abdulqadir J.; Al-Jurf, Rana M.; Ismail, Mohamed A.; AlSharshani, Mohammed M.; AlSayab, Ali A.; Ben-Omran, Tawfeg I.; Khatib, Rani B.; Yassin, Mohamed A.

    2016-01-01

    BACKGROUND Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients’ treatments fail. AIM This study investigates the correlation between patient adherence and failure of TKIs’ treatment in a follow-up study. METHODS This is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd). The 9-item Morisky Medication Adherence Scale, medication possession ratio (MPR) calculation, and the electronic medical records are used for identifying potential factors that influence adherence. Clinical outcomes are assessed according to the European Leukemia Net 2013 guidelines via reverse transcriptase quantitative polymerase chain reaction measurement of the level of BCR-ABL1 transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure. RESULTS A total of 36 CML patients (5 citizens and 31 noncitizen residents) consented to participate in the study. The overall mean MEMS score was 89. Of the 36 patients, 22 (61%) were classified as adherent (mean: 95) and 14 (39%) were classified as nonadherent (mean: 80.2). Adherent patients were significantly more likely to obtain optimal response (95%) compared to the nonadherent group (14.3%; P health-care teams, doctors, nurses, pharmacists, and patients are essential components for maximizing the benefits of TKI therapy and could rectify this problem. The preliminary results show that patients’ response to treatment may be directly linked to patients’ adherence to treatment. However, further in-depth and specific analysis may be necessary in a larger cohort. PMID:27721664

  16. Lichenoid drug eruption due to imatinib mesylate.

    Science.gov (United States)

    Bhatia, Anuradha; Kanish, Bimal; Chaudhary, Paulina

    2015-01-01

    Imatinib mesylate is a selective tyrosinase kinase inhibitor which has revolutionized the treatment of chronic myeloid leukemia. It is also used in gastrointestinal stromal tumors and dermatofibrosarcoma protruberans. Cutaneous adverse reactions are the most common nonhematological side effects secondary to imatinib. Nonlichenoid reactions are common, while lichenoid reactions are rare. We report a case of lichenoid drug eruption due to imatinib. As the indications and use of imatinib are increasing, the incidences of adverse effects, including cutaneous ones, are likely to increase. Some of the reactions may be severe enough to warrant discontinuation of the drug. The physicians should be aware of this morphological entity, which is usually benign and does not warrant withdrawal of the drug.

  17. One-stage laparoscopic resection for a large gastric gastrointestinal stromal tumor and synchronous liver metastases following preoperative imatinib therapy: A case report

    OpenAIRE

    2013-01-01

    Laparoscopic partial gastrectomy without lymph node dissection has been accepted worldwide for the treatment of small gastric gastrointestinal stromal tumors (GISTs). However, the role of laparoscopic surgery in the treatment of large gastric GISTs remains under debate due to the risk of tumor spillage or rupture of the tumor capsule leading to peritoneal seeding. To the best of our knowledge, one-stage laparoscopic resection for a large gastric GIST and synchronous liver metastases following...

  18. Lack of Association of Multidrug Resistance Gene-1 Polymorphisms with Treatment Outcome in Chronic Myeloid Leukemia Patients Treated with Imatinib

    Directory of Open Access Journals (Sweden)

    Yaya Kassogue

    2015-10-01

    Full Text Available Background: Despite the impressive results obtained with imatinib, inadequate response or resistance are observed in certain patients. It is known that imatinib is a substrate of a multidrug resistance gene (MDR1. Thus, interindividual genetic differences linked to single nucleotide polymorphisms in MDR1 may influence the metabolism of imatinib. The present study has aimed to examine the impact of MDR1 polymorphisms on the hematologic and cytogenetic responses in 70 chronic myeloid leukemia patients who received imatinib. Methods: We used a polymerase chain reaction followed by restriction fragment length polymorphism to identify different profiles of 1236C>T, 2677G>T and 3435C>T in MDR1. Results: The distribution of the three SNPs in responders and poor responders did not show any particular trend (P>0.05. The T allele was slightly higher in responders, but not significantly regardless of the type of SNP (40.3% vs. 33.8% for 1236C>T; 25% vs. 14.7% for 2677G>T and 33.3% vs. 22% for 3435C>T. The dominant model showed a similar trend (P>0.05. Diplotypes composed by the T allele in different exons were frequent in responders. Haplotype analysis showed that 1236C-2677G-3435C was slightly higher in poor responders (60.02% compared to responders (50.42%. However, 1236T-2677T-3435T was frequent in responders (16.98% compared to poor responders (13.1%. Overall, none of the haplotypes were associated with IM response in our cohort (global haplotype association test, P=0.39. Conclusion: The identification of 1236C>T, 2677G>T and 3435C>T polymorphisms may not be advantageous to predict imatinib response for our chronic myeloid leukemia patients.

  19. Development of a specific and sensitive enzyme-linked immunosorbent assay for the quantification of imatinib.

    Science.gov (United States)

    Saita, Tetsuya; Shin, Masashi; Fujito, Hiroshi

    2013-01-01

    Imatinib is an oral tyrosine kinase inhibitor used for first-line treatment of chronic myeloid leukemia. Therapeutic drug monitoring targeting trough plasma levels of about 1000 ng/mL may help to optimize imantinib's therapeutic effect. This paper reports a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for a pharmacokinetic evaluation of imatinib. Anti-imatinib antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin and succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. Enzyme labeling of imatinib with horseradish peroxidase was similarly performed using succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. A simple ELISA for imatinib was developed using the principle of direct competition between imatinib and the enzyme marker for anti-imatinib antibody which had been adsorbed by the plastic surface of a microtiter plate. Serum imatinib concentrations lower than 40 pg/mL were reproducibly measurable using the ELISA. This ELISA was specific to imatinib and showed very slight cross-reactivity (1.2%) with a major metabolite, N-desmethyl imatinib. Using this assay, drug levels were easily measured in the blood of mice after their oral administration of imatinib at a single dose of 50 mg/kg. The specificity and sensitivity of the ELISA for imatinib should provide a valuable new tool for use in therapeutic drug monitoring and pharmacokinetic studies of imatinib.

  20. Preoperative distress predicts persistent pain after breast cancer treatment

    DEFF Research Database (Denmark)

    Mejdahl, Mathias Kvist; Mertz, Birgitte Goldschmidt; Bidstrup, Pernille Envold Hansen;

    2015-01-01

    at the Department of Breast Surgery, Rigshospitalet, Denmark, were invited to participate in the study. Patients filled out a questionnaire preoperatively, and 4 and 8 months after surgery. Preoperative distress was measured with the Distress Thermometer (DT; 11-point scale, 0-10). We examined the association...

  1. Fluid retention associated with imatinib treatment in patients with gastroenterol stromal: Quantitative radiologic assessment and implications for management

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Won; Shinagare, Atul B.; Krajewski, Katherine M.; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikihil H. [Dept. of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Pyo, Jun Hee [The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston (United States)

    2015-04-15

    We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.

  2. Serial splintage: Preoperative treatment of upper limb contracture.

    Science.gov (United States)

    Puri, Vinita; Khare, Nishant; Venkateshwaran, N; Bharadwaj, Sumit; Choudhary, Sushant; Deshpande, Omkarnath; Borkar, Rupali

    2013-09-01

    The present study aimed to study the efficacy of preoperative splints in treatment of upper limb contractures and to evaluate the response of contracture to splints depending on the etiology and the joint involved. Ninety joints of 42 patients were studied. Patients age, gender, etiology, duration of contracture, contracture site and joint and type of contracture was noted. The range of motion of the involved joint was recorded. Serial static splints made of thermoplastic material were applied after customizing them for each patient. The range of motion and percentage movement was recorded at weekly interval and the splints were modified as per need. Time taken to reach a plateau stage was noted. To compare the statistical significance between two groups and more than two groups of continuous variable unpaired t-test and one way ANOVA respectively was applied. We considered differences to be statistically significant when the p value was below 0.05. The strength of relationship between the two continuous variables was analyzed by Pearson correlation analysis. Etiological factors were thermal burns (36.7%), electrical burns (13.3%), post traumatic (35.6%) and post cellulitis (14.4%). Age ranged from 2 to 70 years with a mean of 28.9±13.4 years. Sixty-two patients treated were males (68.9%) and 28 were female (31.1%). The mean range of motion present across all joints before starting the therapy was 54.7±23.6 degrees. The mean improvement in contracture angle obtained by serial splintage was 37.4±28.1 degrees. The mean time taken to achieve plateau was 23.6±3.2 days. Maximum improvement was seen in thermal burn contractures (41.2±30.3 degrees). Least improvement was seen in contractures due to cellulitis (6.5±16.2 degrees). This finding was statistically significant [F(3,86)=4.25, p=0.005]. Significant difference was seen in response to therapy based on the joint involved [F(3,86)=3.36, p=0.02]. Highest improvement in the range of motion was seen in the

  3. [A case report of two-term surgery for focal progression of a huge liver metastasis and peritoneal dissemination from gastrointestinal stromal tumor during imatinib mesylate treatment].

    Science.gov (United States)

    Toyokawa, Takahiro; Teraoka, Hitoshi; Kitayama, Kisyu; Nomura, Shinya; Kanehara, Isao; Nishino, Hiroji

    2014-03-01

    We report a patient who underwent 2-term surgery to treat focal progression of a huge liver metastasis and peritoneal dissemination from a gastric gastrointestinal stromal tumor(GIST)during imatinib mesylate treatment. A 59-year-old man underwent an emergency surgery for perforative peritonitis caused by gastric GIST in June 2006 and a partial resection of the stomach in September 2006. Four years later, abdominal computed tomography(CT)detected a huge liver tumor that occupied the entire right lobe. We initiated imatinib mesylate treatment(400mg/day), and the patient maintained stable disease for several months. However, focal progression of the huge liver tumor and a peritoneal tumor at the splenic hilum were revealed by CT; therefore, an extended right hepatic resection was performed in August 2011 and a distal pancreatectomy, splenectomy, and partial resection of the stomach were performed in February 2012. The patient died of the primary disease at 16 months after the hepatic resection for focal progression.

  4. Hypoxia- or PDGF-BB-dependent paxillin tyrosine phosphorylation in pulmonary hypertension is reversed by HIF-1α depletion or imatinib treatment.

    Science.gov (United States)

    Veith, C; Zakrzewicz, D; Dahal, B K; Bálint, Z; Murmann, K; Wygrecka, M; Seeger, W; Schermuly, R T; Weissmann, N; Kwapiszewska, G

    2014-12-01

    Chronic exposure to hypoxia induces a pronounced remodelling of the pulmonary vasculature leading to pulmonary hypertension (PH). The remodelling process also entails increased proliferation and decreased apoptosis of pulmonary arterial smooth muscle cells (PASMC), processes regulated by the cytoskeletal protein paxillin. In this study, we aimed to examine the molecular mechanisms leading to deregulation of paxillin in PH. We detected a time-dependent increase in paxillin tyrosine 31 (Y31) and 118 (Y118) phosphorylation following hypoxic exposure (1 % O2) or platelet-derived growth factor (PDGF)-BB stimulation of primary human PASMC. In addition, both, hypoxia- and PDGF-BB increased the nuclear localisation of phospho-paxillin Y31 as indicated by immunofluorescence staining in human PASMC. Elevated paxillin tyrosine phosphorylation in human PASMC was attenuated by hypoxia-inducible factor (HIF)-1α depletion or by treatment with the PDGF-BB receptor antagonist, imatinib. Moreover, we observed elevated paxillin Y31 and Y118 phosphorylation in the pulmonary vasculature of chronic hypoxic mice (21 days, 10 % O2) which was reversible by imatinib-treatment. PDGF-BB-dependent PASMC proliferation was regulated via the paxillin-Erk1/2-cyclin D1 pathway. In conclusion, we suggest paxillin up-regulation and phosphorylation as an important mechanism of vascular remodelling underlying pulmonary hypertension.

  5. Imatinib-induced postoperative periorbital purpura: GASP (Gleevec-Associated Surgical Purpura) in a woman with imatinib-treated chronic myelogenous leukemia.

    Science.gov (United States)

    Anzalone, C Lane; Cohen, Philip R; Kurzrock, Razelle; Cortes, Jorge E

    2014-01-15

    Imatinib mesylate is a selective tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukemia. Ocular side effects of imatinib include periorbital edema, which may become so severe as to obstruct the visual field. The purpose of this case study is to describe the clinical characteristics of imatinib- induced postoperative periorbital purpura. We retrospectively reviewed the medical literature using PubMed, searching the terms edema, Gleevec, imatinib, periorbital, postoperative and purpura. Patient reports and previous reviews of the subject were critically assessed and the salient features are presented. Three patients have undergone surgery to reduce the imatinib-induced periorbital edema; two of these individuals have developed imatinib-induced postoperative periorbital purpura. We recommend discontinuing imatinib usage one week prior to periorbital surgery and not resuming therapy until the eighth postoperative day.

  6. Profile of imatinib in pediatric leukemia

    Directory of Open Access Journals (Sweden)

    Burke MJ

    2014-02-01

    Full Text Available Michael J BurkeDepartment of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI, USAAbstract: Using targeted therapy for treatment of cancer has become the paradigm to which clinical trials aspire. Imatinib, the BCR-ABL1 tyrosine kinase inhibitor (TKI, was the first of its kind to specifically target and inhibit the underlying Philadelphia chromosome (Ph+ oncogene found to be driving chronic myeloid leukemia in adults, and has since become standard of care for the treatment of chronic myeloid leukemia in children. Imatinib, with its ability to target Ph+ leukemia, has been successfully incorporated into the treatment of not only pediatric chronic myeloid leukemia but also Ph+ acute lymphoblastic leukemia. With the incorporation of imatinib into combination chemotherapy for pediatric Ph+ acute lymphoblastic leukemia, current survival rates are far higher than at any other time for this once dreadful disease. With more children today receiving treatment with imatinib for either chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia, knowledge is accumulating surrounding the short-term and long-term toxicities observed in children, adolescents, and young adults treated with this TKI. In summary, the TKI imatinib has made a historic impact in the treatment of pediatric Ph+ leukemias, transforming what were once very high-risk diseases with considerable morbidity and mortality into ones that are now very treatable but with a new awareness surrounding the long-term toxicities that may come with this price for cure.Keywords: imatinib, leukemia, lymphoblastic leukemia, chronic myeloid leukemia, pediatric

  7. Sensitivity of imatinib-resistant T315I BCR-ABL CML to a synergistic combination of ponatinib and forskolin treatment.

    Science.gov (United States)

    Oaxaca, Derrick M; Yang-Reid, Sun Ah; Ross, Jeremy A; Rodriguez, Georgialina; Staniswalis, Joan G; Kirken, Robert A

    2016-09-01

    Tyrosine kinase inhibitors (TKIs) have dramatically improved the life expectancy of patients suffering from chronic myeloid leukemia (CML); however, patients will eventually develop resistance to TKI therapy or adverse side effects due to secondary off-target mechanisms associated with TKIs. CML patients exhibiting TKI resistance are at greater risk of developing an aggressive and drug-insensitive disease. Drug-resistant CML typically arises in response to spontaneous mutations within the drug binding sites of the targeted oncoproteins. To better understand the mechanism of drug resistance in TKI-resistant CML patients, the BCR-ABL transformed cell line KCL22 was grown with increasing concentrations of imatinib for a period of 6 weeks. Subsequently, a drug-resistant derivative of the parental KCL22 cell line harboring the T315I gatekeeper mutation was isolated and investigated for TKI drug sensitivity via multi-agent drug screens. A synergistic combination of ponatinib- and forskolin-reduced cell viability was identified in this clinically relevant imatinib-resistant CML cell line, which also proved efficacious in other CML cell lines. In summary, this study provides new insight into the biological underpinnings of BCR-ABL-driven CML and potential rationale for investigating novel treatment strategies for patients with T315I CML.

  8. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump

    NARCIS (Netherlands)

    H. Burger (Herman); H. van Tol; A.W.M. Boersma (Anton); M. Brok (Mariël); E.A.C. Wiemer (Erik); G. Stoter (Gerrit); K. Nooter (Kees)

    2004-01-01

    textabstractImatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular

  9. Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management

    Science.gov (United States)

    Shinagare, Atul B.; Krajewski, Katherine M.; Pyo, Junhee; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.

    2015-01-01

    Objective We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. Materials and Methods In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. Results The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Conclusion Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management. PMID:25741192

  10. Behandling af ideopatisk hypereosinofilt syndrom med imatinib

    DEFF Research Database (Denmark)

    Sørensen, Anne Louise; Larsen, Herdis

    2008-01-01

    We here report a case of idiopathic hypereosinophilic syndrome with prompt response to treatment with imatinib. The patient presented with chest pain, myalgias, fatigue and weakness. Blood tests and bone marrow examination revealed striking eosinophilia. Clonal or reactive disorders were excluded...

  11. International preoperative rectal cancer management: staging, neoadjuvant treatment, and impact of multidisciplinary teams.

    LENUS (Irish Health Repository)

    Augestad, Knut M

    2010-11-01

    Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates.

  12. Overexpression of P-glycoprotein induces acquired resistance to imatinib in chronic myelogenous leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Xing-Xiang Peng; Amit K. Tiwari; Hsiang-Chun Wu; Zhe-Sheng Chen

    2012-01-01

    Imatinib,a breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) tyrosine kinase inhibitor (TKI),has revolutionized the treatment of chronic myelogenous leukemia (CML).However,development of multidrug resistance(MDR) limits the use of imatinib.In the present study,we aimed to investigate the mechanisms of cellular resistance to imatinib in CML.Therefore,we established an imatinib-resistant human CML cell line (K562-imatinib) through a stepwise selection process.While characterizing the phenotype of these cells,we found that K562-imatinib cells were 124.6-fold more resistant to imatinib than parental K562 cells.In addition,these cells were cross-resistant to second- and third-generation BCR-ABL TKIs.Western blot analysis and reverse transcription-polymerase chain reaction(RT-PCR) demonstrated that P-glycoprotein (P-gp) and MDR1 mRNA levels were increased in K562-imatinib cells.In addition,accumulation of [14C]6-mercaptopurine (6-MP) was decreased,whereas the ATP-dependent efflux of [14C] 6-MP and [3H]methotrexate transport were increased in K562-imatinib cells.These data suggest that the overexpression of P-gp may play a crucial role in acquired resistance to imatinib in CML K562-imatinib cells.

  13. Exploiting mitochondrial dysfunction for effective elimination of imatinib-resistant leukemic cells.

    Directory of Open Access Journals (Sweden)

    Jérome Kluza

    Full Text Available Challenges today concern chronic myeloid leukemia (CML patients resistant to imatinib. There is growing evidence that imatinib-resistant leukemic cells present abnormal glucose metabolism but the impact on mitochondria has been neglected. Our work aimed to better understand and exploit the metabolic alterations of imatinib-resistant leukemic cells. Imatinib-resistant cells presented high glycolysis as compared to sensitive cells. Consistently, expression of key glycolytic enzymes, at least partly mediated by HIF-1α, was modified in imatinib-resistant cells suggesting that imatinib-resistant cells uncouple glycolytic flux from pyruvate oxidation. Interestingly, mitochondria of imatinib-resistant cells exhibited accumulation of TCA cycle intermediates, increased NADH and low oxygen consumption. These mitochondrial alterations due to the partial failure of ETC were further confirmed in leukemic cells isolated from some imatinib-resistant CML patients. As a consequence, mitochondria generated more ROS than those of imatinib-sensitive cells. This, in turn, resulted in increased death of imatinib-resistant leukemic cells following in vitro or in vivo treatment with the pro-oxidants, PEITC and Trisenox, in a syngeneic mouse tumor model. Conversely, inhibition of glycolysis caused derepression of respiration leading to lower cellular ROS. In conclusion, these findings indicate that imatinib-resistant leukemic cells have an unexpected mitochondrial dysfunction that could be exploited for selective therapeutic intervention.

  14. The role of preoperative pulmonary function tests in the surgical treatment of extremely severe scoliosis

    OpenAIRE

    Lao, Lifeng; Weng, Xisheng; Qiu, Guixing; Shen, Jianxiong

    2013-01-01

    Background The patients with extremely severe spinal deformity are commonly considered high-risk candidates for surgical treatment because of their underlying lung disease. Currently, little has been reported about the postoperative pulmonary complication events in this population. This retrospective study sought to evaluate preoperative pulmonary function tests in the surgical treatment of extremely severe scoliosis. Methods Preoperative forced vital capacity (FVC), FVC ratio, forced expirat...

  15. Study on adherence to treatment with imatinib in chronic myeloid leukaemia and its association with therapeutic response.

    Science.gov (United States)

    García-Queiruga, Marta; Martínez-López, Laura María; Martín-Herranz, María Isabel; Seoane-Pillado, Teresa; Fernández-Gabriel, Elena; Calleja-Chuclá, Teresa

    2016-05-01

    Objetivo: El objetivo es evaluar el grado de adhesión terapéutica a imatinib en pacientes con leucemia mieloide crónica y su relación con la respuesta terapéutica. Material y métodos: Estudio realizado en octubre 2013-marzo 2014 que incluye a pacientes diagnosticados de leucemia mieloide crónica en tratamiento con imatinib en el hospital. Se evaluó la adhesión terapéutica mediante el cuestionario estandarizado Morisky-Green y el registro de dispensaciones de medicación. Se excluyeron aquellos que no completaron 6 meses de tratamiento y/o no realizaron el cuestionario. La respuesta terapéutica se evaluó siguiendo guías clínicas. Se realizó el análisis descriptivo de variables y correlación mediante test Chi-cuadrado de Pearson. Resultados: Se incluyeron 31 pacientes. Al evaluar el grado de asociación entre variables de respuesta y adhesión terapéutica: 1. La respuesta molecular mayor fue alcanzada por el 68,4% de los pacientes con alta adhesión y por el 75% de los pacientes con adhesión media. 2. La respuesta molecular completa fue alcanzada por el 57,9% de los pacientes con alta adhesión y por el 58,3% de los pacientes con adhesión media. No se observaron diferencias estadísticamente significativas en las variables de respuesta entre pacientes con adhesión terapéutica alta y media. No se observó asociación entre el grado de adhesión y la respuesta terapéutica. Conclusiones: No podemos afirmar que el distinto grado de adhesión terapéutica influya en la respuesta al imatinib, aunque debería considerarse en casos de fallo terapéutico o respuesta subóptima.

  16. [The role of magnetic resonance imaging to select patients for preoperative treatment in rectal cancer].

    Science.gov (United States)

    Rödel, Claus; Sauer, Rolf; Fietkau, Rainer

    2009-08-01

    Traditionally, the decision to apply preoperative treatment for rectal cancer patients has been based on the T- and N-category. Recently, the radial distance of the tumor to the circumferential resection margin (CRM) has been identified as an important risk factor for local failure. By magnetic resonance imaging (MRI) this distance can be measured preoperatively with high reliability. Thus, selected groups have started to limit the indication for preoperative therapy to tumors extending to - or growing within 1 mm from - the mesorectal fascia (CRM+). Pros and cons of this selected approach for preoperative treatment and first clinical results are presented. Prerequisites are the availability of modern high-resolution thin-section MRI technology as well as strict quality control of MRI and surgical quality of total mesorectal excision (TME). By selecting patients with CRM-positive tumors on MRI for preoperative therapy, only approximately 35% patients will require preoperative radiotherapy (RT) or radiochemotherapy (RCT). However, with histopathologic work-up of the resected specimen after primary surgery, the indication for postoperative RCT is given for a rather large percentage of patients, i.e., for pCRM+ (5-10%), intramesorectal or intramural excision (30-40%), pN+ (30-40%). Postoperative RCT, however, is significantly less effective and more toxic than preoperative RCT. A further point of concern is the assertion that patients, in whom a CRM-negative status is achieved by surgery alone, do not benefit from additional RT. Data of the Dutch TME trial and the British MRC (Medical Research Council) CR07 trial, however, suggest the reverse. To omit preoperative RT/RCT for CRM-negative tumors on MRI needs to be further investigated in prospective clinical trials. The German guidelines for the treatment of colorectal cancer 2008 continue to indicate preoperative RT/RCT based on the T- and N-category.

  17. Therapeutic drug monitoring for imatinib: Current status and Indian experience.

    Science.gov (United States)

    Arora, Brijesh; Gota, Vikram; Menon, Hari; Sengar, Manju; Nair, Reena; Patial, Pankaj; Banavali, S D

    2013-07-01

    Imatinib is the current gold standard for treatment of chronic myeloid leukemia (CML). Recent pharmacokinetic studies have shown considerable variability in trough concentrations of imatinib due to variations in its metabolism, poor compliance, or drug-drug interactions and highlighted its impact on clinical response. A trough level close to 1000 ng/mL, appears to be correlated with better cytogenetic and molecular responses. Therapeutic Drug Monitoring (TDM) for imatinib may provide useful added information on efficacy, safety and compliance than clinical assessment alone and help in clinical decision making. It may be particularly helpful in patients with suboptimal response to treatment or treatment failure, severe or rare adverse events, possible drug interactions, or suspected nonadherence. Further prospective studies are needed to confirm relationship between imatinib plasma concentrations with response, and to define effective plasma concentrations in different patient populations.

  18. Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib

    OpenAIRE

    Moryoussef, Frédérick; Dhooge, Marion; Volet, Julien; Barbe, Coralie; Brezault, Catherine; Hoeffel, Christine; Coriat, Romain; Bouché, Olivier

    2015-01-01

    Background Imatinib is a long-term, oral, targeted therapy for high-risk resected and advanced gastrointestinal stromal tumours (GIST). It is known that sarcopenia affects prognosis and treatment tolerance in patients with various solid cancers. We analysed lumbar skeletal muscle index changes in imatinib-treated GIST patients. Imatinib tolerance was also assessed to evaluate the influence of pre-treatment sarcopenia. Methods Thirty-one patients with advanced (n = 16) or high-risk resected (n...

  19. Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Wang, Dian [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Haas, Rick L.M. [Department of Radiotherapy, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Catton, Charles N. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Indelicato, Daniel J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Kirsch, David G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Roberge, David [Department of Radiation Oncology, Centre Hospitalier de l' Université de Montreal, Montreal, Quebec (Canada); Salerno, Kilian [Department of Radiation Oncology, Roswell Park Cancer Institute, Buffalo, New York (United States); Deville, Curtiland [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Sidney Kimmel Cancer Center, Washington, DC (United States); Guadagnolo, B. Ashleigh [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); O' Sullivan, Brian [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Petersen, Ivy A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Le Pechoux, Cecile [Department of Radiotherapy, Institut Gustave-Roussy, Villejuif (France); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-07-01

    Purpose: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. Methods and Materials: An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Results: Treatment guidelines for preoperative RT for RPS are presented. Conclusions: An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy

  20. Preoperative embolization in surgical treatment of spinal metastases

    DEFF Research Database (Denmark)

    Clausen, Caroline; Dahl, Benny; Frevert, Susanne Christiansen;

    2015-01-01

    AND METHODS: This single-blind, randomized (1:1), controlled, parallel-group, single-center trial was approved by the Danish National Committee on Biomedical Research Ethics and was conducted from May 2011-March 2013. Participants (N = 45) were scheduled for decompression and posterior thoracic/lumbar spinal...... instrumentation and randomly assigned to either preoperative embolization (n = 23) or a control group (n = 22). The primary outcome was intraoperative blood loss. Secondary outcomes were perioperative blood loss, allogeneic RBC transfusion, and surgery time. Analyses were performed by intention-to-treat. RESULTS......: The intention-to-treat analysis included 45 patients. Mean intraoperative blood loss did not differ significantly (P = .270) between the embolization group (618 mL [SD, 282 mL]) and the control group (735 mL [SD, 415 mL]). There was also no significant difference in allogeneic RBC transfusion (P = .243...

  1. Imatinib Use in Pregnancy

    Directory of Open Access Journals (Sweden)

    Michael J Webb

    2012-12-01

    Full Text Available The outcome in patients with chronic myeloid leukemia (CML has dramatically improved over the last decade due to the widespread use of novel tyrosine kinase inhibitors such as imatinib. As overall survival has improved, the number of women with CML that wish to become pregnant has increased. As such, attending physicians are faced with a dilemma-continue life-prolonging medication to treat the cancer, or interrupt its use due to its potential teratogenicity. Herein we describe 2 CML patients that gave birth. Case 1 was managed via substitution of imatinib with interferon. The patient’s child underwent genetic evaluation at age 3 years, achieved normal developmental milestones, and despite being shorter than his peers was proportional. In terms of morphology, the child had clinodactyly, short fifth fingers, and slightly downward slanting palpebral fissures, but otherwise appeared normal. In case 2 imatinib was continued throughout the pregnancy. This patient’s child underwent postpartum evaluation by a geneticist and was observed to be morphologically normal, except for clinodactyly and low-set ears.

  2. Formulation and characterization of microspheres loaded with imatinib for sustained delivery.

    Science.gov (United States)

    Ramazani, F; Chen, W; Van Nostrum, C F; Storm, G; Kiessling, F; Lammers, T; Hennink, W E; Kok, R J

    2015-03-30

    The aim of this study was the development of imatinib-loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres with high loading efficiency which can afford continuous release of imatinib over a prolonged period of time. Imatinib mesylate loaded PLGA microspheres with a size of 6-20 μm were prepared by a double emulsion (W1/O/W2) method using dichloromethane as volatile solvent. It was found that the microspheres were spherical with a non-porous surface; imatinib loading efficiency (LE) was highly dependent on the pH of the external water phase (W2). By increasing the pH of W2 phase above the highest pKa of imatinib (pKa 8.1), at which imatinib is mainly uncharged, the LE increased from 10% to 90% (pH 5.0 versus pH 9.0). Conversely, only 4% of its counter ion, mesylate, was retained in the microspheres at the same condition (pH 9.0). Since mesylate is highly water soluble, it is unlikely that it partitions into the organic phase. We demonstrated, using differential scanning calorimetry (DSC), that imatinib was molecularly dispersed in the polymeric matrix at loadings up to 8.0%. At higher drug loading, imatinib partially crystallized in the matrix. Imatinib microspheres released their cargo during three months by a combination of diffusion through the polymer matrix and polymer erosion. In conclusion, we have formulated imatinib microspheres with high LE and LC. Although we started with a double emulsion of imatinib mesylate, the obtained microspheres contained imatinib base which was mainly molecularly dispersed in the polymer matrix. These microspheres release imatinib over a 3-month period which is of interest for local treatment of cancer.

  3. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Seshadri Ramakrishnan

    2009-01-01

    Full Text Available Aim : To study the role of neoadjuvant imatinib mesylate in downsizing tumors in patients with locally advanced nonmetastatic gastrointestinal stromal tumors (GISTs, thus improving the possibility of complete resection. Materials and Methods : We used neoadjuvant imatinib in six patients with locally advanced GISTs, at a dose of 400 mg daily, given orally in all patients for a median period of 3.5 months (range 1-20 months. All patients had a computerized tomography scan (CT scan once before starting the treatment and a repeat CT scan 1 month after starting imatinib. Some patients had another CT scan done at 3 months. The tumor volume was calculated using the formula V=4/3 πr 3 . Results : Following imatinib therapy, the median reduction in the tumor volume was 40% (range 20-50%. Four of the six patients underwent successful complete resection of the tumor following neoadjuvant imatinib for a median period of 2 months, and are disease free after a median follow-up of 10.5 months (range 3-20 months. Two patients in whom the tumors were deemed to be operable after downsizing refused surgery and are continuing imatinib. Imatinib did not produce serious toxicity in any patient. Conclusion : Neoadjuvant imatinib can be used successfully in patients with locally advanced nonmetastatic GISTs to improve the rates of complete resection and reduce the chance of tumor spill. The optimal duration of neoadjuvant treatment needs to be tailored based on response assessment at frequent intervals to identify the ideal window period for surgery.

  4. The teratogenic effects of imatinib mesylate on rat fetuses

    Directory of Open Access Journals (Sweden)

    M.M. El Gendy

    2015-01-01

    Full Text Available Imatinib mesylate, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukemia and gastrointestinal stromal tumors. The aim of the present study is to investigate the effects of imatinib mesylate on the pregnant rats and their fetuses. Pregnant rats were divided into three groups; the first group served as a control group. The second and third groups were orally administered imatinib at doses of 36 mg/kg body weight or 54 mg/kg b.wt. on gestation days (SDs 6 through 13 or SDs 13 through 19, respectively. All animals were sacrificed on the 20th day of gestation. Treatment with imatinib caused a reduction of maternal body weight gain, uterine and placental weights, increased rate of abortion and fetal resorptions. High dose of imatinib caused fetal congenital deformities represented in harelip, contraction of the fore limbs, and paralysis of the hind limbs, exencephaly, encephalocoele and distended abdominal wall, besides occurrence of wavy ribs and absence of other ribs in addition to skeletal growth retardation and lack of ossification of the most skeletal elements. The present work concluded that imatinib is teratogenic when given orally to pregnant rats at 54 mg/kg b.wt. and causes direct maternal or developmental toxicity.

  5. Imatinib-induced fatal acute liver failure

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia (CML) in blast crisis, accelerated or chronic phase, and also for advanced gastrointestinal stromal tumors. Severe hepatic toxicity and three deaths from hepatic failure have been reported. We report the case of a 51-year-old woman who was admitted to our institution with severe acute hepatitis. She was diagnosed with CML and began treatment with imatinib mesylate at a dose of 400 mg/d.Five months after beginning treatment, she developed severe hepatitis associated with coagulopathy, and was admitted to our institution. She had been consuming acetaminophen 500-1000 mg/d after the onset of symptoms. She had a progressive increase in bilirubin level and a marked decrease of clotting factor Ⅴ. Five days after admission, grade Ⅱ encephalopathy developed and she was referred for liver transplantation. Her clinical condition progressively deteriorated, and 48 h after being referred for transplantation she suffered a cardiac arrest and died. This report adds concern about the possibility of imatinib-mesylate-induced hepatotoxicity and liver failure, particularly in the case of concomitant use with acetaminophen. Liver function tests should be carefully monitored during treatment and, with the appearance of any elevation of liver function tests, treatment should be discontinued.

  6. Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

    Science.gov (United States)

    Ottmann, Oliver G; Wassmann, Barbara; Pfeifer, Heike; Giagounidis, Aristoteles; Stelljes, Matthias; Dührsen, Ulrich; Schmalzing, Marc; Wunderle, Lydia; Binckebanck, Anja; Hoelzer, Dieter

    2007-05-15

    Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known. Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (Ind(IM)) or multiagent, age-adapted chemotherapy (Ind(chemo)). Imatinib was subsequently coadministered with consolidation chemotherapy. In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to Ind(IM) and 50% in patients allocated to Ind(chemo) (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Ind(chemo); none failed imatinib induction. Severe adverse events were significantly more frequent during Ind(chemo) (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% +/- 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002). In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction. (c) 2007 American Cancer Society

  7. Preoperative radiotherapy in rectal cancer treatment -- is it really a gold standard?

    Science.gov (United States)

    Pătraşcu, Tr; Doran, H; Mihalache, O

    2014-01-01

    Preoperative radiotherapy in the treatment of rectal cancer was thought to be an achievement of similar importance to total mesorectal excision (TME), for the therapeutic management of rectal malignancies. However, numerous criticisms have been discussed in this field lately. We have analysed the two main purposes of preoperative radiation: possible sphincter preservation and the conversion of a non-resectable tumor into a resectable one in a series of 31 consecutive patients, operated in our clinic. In 20 of them, preoperative radio chemoradiotherapy was applied, while 11 patients were firstly operated and then irradiated. The surgical procedure included total mesorectal excision in 30 patients, as part of a low anterior resection,in 13 cases and of an abdominal perineal resection, in the other 17 cases. We have found that preoperative radiotherapy improves the local recurrence rate but has no influence on the overall survival rate. However, we should not overlook the adverse effects of this method: toxicity of radiotherapy on the small bowel and the urinary bladder, the healing of the perineal wounds and the risk of anastomotic leaks. We concluded in favor of elective preoperative radiotherapy in selected cases: any T4 tumors, T3 tumors which threaten the mesorectal fascia on MRI, whenever there is a suspicion of nodal involvement and also for very low tumors. Celsius.

  8. Clinicopathological studies on preoperative three combined treatments with hyperthermo-chemo-radiotherapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Yuji [Kyoto Prefectural Univ. of Medicine (Japan)

    1995-08-01

    To prevent local recurrence of rectal cancer postoperatively, we treated patients using preoperative hyperthermia (5-6 times), irradiation (total 30 Gy) and a 5-Fluorouracil suppository (2000-2500 mg). The subjects were 31 patients given combined preoperative treatments and 28 patients given surgery alone. The results were as follows: Histologically, therapeutic effects were recognized in 80.6% of the combined treatments group. The mean distance from the adventitia to the site of cancer infiltration was 6.44 mm in the combined treatments group and 3.35 mm in the surgery alone group. The difference between the two was significant (p<0.05). The combined treatments produced a reduced tumor infiltration into the anal side, and resulted in making a safe margin for anastomosis. The rate of local recurrence in the combined treatments group was less than that of the surgery alone group. No systematic side effects or severe complications were observed during hospitalization in the combined treatments group. The survival rate of the combined treatments group was higher than that of the surgery alone group. It was considered that combined preoperative treatments for rectal cancer is beneficial to expand indications of super low anterior resection. (author).

  9. The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

    Energy Technology Data Exchange (ETDEWEB)

    Goerres, G.W.; Hany, T.F.; Schulthess, G.K. von [University Hospital Zurich, Division of Nuclear Medicine, Zurich (Switzerland); Stupp, R.; Luthi, F.; Leyvraz, S. [University of Lausanne Medical Centre, Multidisciplinary Oncology Centre, Lausanne (Switzerland); Barghouth, G.; Schnyder, P. [University of Lausanne Medical Centre, Department of Radiology, Lausanne (Switzerland); Pestalozzi, B. [University Hospital Zurich, Department of Oncology, Zurich (Switzerland); Dizendorf, E. [University Hospital Zurich, Division of Nuclear Medicine, Zurich (Switzerland); International Tomography Center, Novosibirsk (Russian Federation)

    2005-02-01

    Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to standard sarcoma chemotherapy. Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography (ceCT) and positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG). The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging. All patients with GIST undergoing PET or PET/CT examinations were prospectively included in this study, and the median overall survival, time to progression and treatment duration were documented. The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging. Data for 34 patients (19 male, 15 female, 21-76 years) undergoing PET or PET/CT for staging or restaging were analysed. In 28 patients, PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity. In contrast, ceCT criteria provided insufficient prognostic power. However, more lesions were found on ceCT images than on PET images, and FDG uptake was sometimes very variable. PET/CT delineated active lesions better than did the combination of PET and ceCT imaging. Both PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients. PET/CT precisely delineates lesions and thus allows for the correct planning of surgical interventions. (orig.)

  10. Optimizing Adherence to Adjuvant Imatinib in Gastrointestinal Stromal Tumor

    Science.gov (United States)

    Tetzlaff, Eric D.; Davey, Monica P.

    2013-01-01

    The increasing use of patient-administered oral anticancer drugs is paralleled by new challenges in maintaining treatment adherence. These challenges are particularly significant with adjuvant therapies for prevention of disease recurrence, where the benefits of ongoing treatment are not readily apparent to patients. Nurse practitioners and physician assistants (collectively referred to as advanced practitioners) play integral roles in providing education on disease and treatment to patients that can increase adherence to oral therapies and ideally improve outcomes. For patients with gastrointestinal stromal tumor (GIST), the oral targeted therapy imatinib has become the mainstay of treatment for advanced and recurrent disease and as adjuvant therapy following surgical resection. Recent data indicate significantly improved overall survival with 3 years vs. 1 year of adjuvant imatinib therapy. Continuous dosing with imatinib is needed for optimal efficacy and to limit additional health-care costs associated with management of disease progression in GIST. However, longer duration of therapy increases the risk of nonadherence. Imatinib adherence rates, as well as factors contributing to nonadherence to adjuvant therapy in routine clinical practice, are discussed in this review. Also explored are practical approaches for improving adherence to adjuvant imatinib therapy through greater patient education, in light of the increased duration of therapy in select patients. PMID:25032004

  11. CLINICAL EFFICACY OF IMATINIB CHA NILE UNITED 12- O- TETRADECANE ACID PHORBOL-13- ACETATE (TPA) IN TREATMENT OF IMATINIB (GLEEVEC) -RESISTANT CHRONIC MYELOID LEUKEMIA (CML) CML PATIENTS%尼勒替尼联合TPA治疗伊马替尼耐药的慢性粒细胞白血病急变期患者的临床疗效

    Institute of Scientific and Technical Information of China (English)

    薛芙蕖

    2011-01-01

    [Objective] To observed clinical efficacy and toxicity of Imatinib Cha Nile United 12 - 0 - tetradecane acid phorbol-13-acetate (TPA) in treatment of imatinib (Gleevec) -resistant chronic myeloid leukemia (CML) CML patients. [Methods] Conventional dose imatinib resistant CML patients with the acute phase 72 patients were randomly divided into two groups, and treated with mesnil or mesnil Imatinib combined TPA, respectively. The liver and kidney function were reviewed each week, and peripheral blood smear were review each week after one month of treatment Blood and bone marrow cells were performed morphological examination every 3 months, cytogenetic and recording adverse events during treatment were observed, and we also recorded hematologic remission rate and cell genetic school response rate. [Results] 6 cases in treatment group showed complete hematologic remission (CHR), 12 cases showed partial hematologic remission (PHR), 12 cases returned to chronic phase, 6 cases failed. The hematologic response rate (including the CHR and PHR) was 50%. 6 cases showed complete cytogenetic remission (CCR), 10 cases showed partial cytogenetic response (PCR), and the total genetic response rate (including the CCR and PCR) was 50% and 44%, respectively. 8 cases in the treatment group shwed complete hematologic remission (CHR), 18 cases showed partial hematologic remission (PHR), 8 cases returned to chronic phase, 2 cases failed, and the hematologic response rate (including the CHR and PHR) was 72.2%. 8 cases showed complete cytogenetic response, 16 cases showed partial cytogenetic response (PCR), and the total rate of genetic response rate was 67%, which was higher than the single use mesnil imatinib treatment group. Between the two groups, the total effective rates of the hematologic remission and cytogenetic response was significant difference. There was no statistical difference in the adverse reactions between the two groups. [Conclusion] Imatinib combined TPA mesnil

  12. Inhibition of c-Kit is not required for reversal of hyperglycemia by imatinib in NOD mice.

    Directory of Open Access Journals (Sweden)

    Janet Lau

    Full Text Available AIM/HYPOTHESIS: Recent studies indicate that tyrosine kinase inhibitors, including imatinib, can reverse hyperglycemia in non-obese diabetic (NOD mice, a model of type 1 diabetes (T1D. Imatinib inhibits c-Abl, c-Kit, and PDGFRs. Next-generation tyrosine kinase inhibitors for T1D treatment should maintain activities required for efficacy while sparing inhibition of targets that might otherwise lead to adverse events. In this study, we investigated the contribution of c-Kit inhibition by imatinib in reversal of hyperglycemia in NOD mice. METHODS: The T670I mutation in c-Kit, which confers imatinib resistance, was engineered into the mouse genome and bred onto the NOD background. Hematopoietic stem cells (HSCs from NOD.c-Kit(T670I mice and NOD.c-Kit(wt littermates were expanded in the presence or absence of imatinib to verify imatinib resistance of the c-Kit(T670I allele. Diabetic mice were treated with imatinib at the onset of hyperglycemia for three weeks, and blood glucose was monitored. RESULTS: In vitro expansion of HSCs from NOD.c-Kit(wt mice was sensitive to imatinib, while expansion of HSCs from NOD.c-Kit(T670I mice was insensitive to imatinib. However, in vivo treatment with imatinib lowered blood glucose levels in both strains of mice. CONCLUSIONS/INTERPRETATION: The HSC experiment confirmed that, in NOD.c-Kit(T670I mice, c-Kit is resistant to imatinib. As both NOD.c-Kit(T670I and NOD.c-Kit(wt mice responded comparably to imatinib, c-Kit inhibition does not substantially contribute to the efficacy of imatinib in T1D. Thus, we conclude that inhibition of c-Kit is not required in next-generation tyrosine kinase inhibitors for T1D treatment, and may be selected against to improve the safety profile.

  13. Tratamento da recidiva da leucemia mielóide crônica após transplante de medula óssea alogênico utilizando mesilato de imatinibe: relato de três casos Treatment of chronic myelogenous leukemia relapse after allogeneic bone marrow transplantation with imatinib mesylate: report of three cases

    Directory of Open Access Journals (Sweden)

    Ronald Pallotta

    2006-06-01

    Full Text Available O mesilato de imatinibe (MI, inibidor seletivo da tirosinoquinase envolvido na patogênese da leucemia mielóide crônica (LMC, tem se constituído como terapia farmacológica de primeira linha para o tratamento desta doença. A infusão de linfócitos do doador (DLI tem sido considerada como tratamento padrão para recidiva da LMC após transplante de medula óssea (TMO alogênico, apesar de estar freqüentemente associado à ocorrência de doença do enxerto contra hospedeiro e mielossupressão. Por apresentar resultados satisfatórios e boa tolerabilidade no tratamento da LMC, os autores empregaram o mesilato de imatinib como terapêutica alternativa à DLI em pacientes que sofreram recidiva após o TMO. Obtiveram sucesso em dois casos, sendo que em um houve retorno comprovado do quimerismo do doador. No terceiro caso houve progressão da doença e o paciente foi encaminhado para segundo TMO. Desta forma, devido ao caráter recente do tema, este estudo descritivo sugere que esta opção terapêutica possa ser estudada como alternativa na recaída pós-TMO.Imatinib mesylate (MI, a selective tyrosine kinase inhibitor involved in the pathogenesis of chronic myelogenous leukemia (CML, has become the first-line treatment for this disease. Donor lymphocyte infusion (DLI has been considered as the standard treatment for relapse after allogeneic bone marrow transplantation (BMT, even though it is frequently associated with graft versus host disease and myelosuppression. Because of the satisfactory results and tolerance of the treatment of CML, the authors used MI as an alternative therapy for DLI in patients that relapsed after BMT. They obtained cytogenetic remission in two cases, with, in one case, proven conversion to the donor chimera. The third case evolved with progression of the disease and a second BMT was required. Since this is a new alternative, this descriptive study suggests it should be considered as an alternative therapy for relapse

  14. Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    Science.gov (United States)

    Mazza, Elena; Brandes, Alba; Zanon, Silvia; Eoli, Marika; Lombardi, Giuseppe; Faedi, Marina; Franceschi, Enrico; Reni, Michele

    2016-01-01

    Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

  15. Idiopathic intracranial hypertension: a possible association with ImatinibIdiopathic intracranial hypertension: a possible association with Imatinib

    Directory of Open Access Journals (Sweden)

    Thomas Baumann

    2011-06-01

    Full Text Available Idiopathic intracranial hypertension (IIH is characterized by an increased intracranial pressure in the absence of a tumor and in the absence of a venous thrombosis. Associated risk factors include obesity and several medications such as tetracyclines. We report a 60-year-old patient who developed IIH under treatment with imatinib. To our knowledge such a possible connection has not been reported in the literature, even though intracranial hypertension is now listed as a rare possible side effect of treatment with imatinib in the Swiss List of Medications Arzneimittelkompendium. It remains to be seen, if further case reports will support this observation.

  16. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

    Science.gov (United States)

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

  17. Lichenoid drug eruption caused by imatinib mesylate in a Chinese patient with gastrointestinal stromal tumor.

    Science.gov (United States)

    Luo, Jing-Ru; Xiang, Xiao-Jun; Xiong, Jian-Ping

    2016-09-01

    Imatinib mesylate, the first agent approved for the treatment of unresectable or metastatic gastrointestinal stromal tumor, is a tyrosine kinase inhibitor targeting (KIT) and the platelet-derived growth factor receptor-α and -β. However, imatinib administration can be accompanied by various adverse events. Here we report a case of Lichenoid drug eruption (LDE) that appeared 24 weeks after commencement of imatinib in a 73-year-old man with gastrointestinal stromal tumor (GIST). The skin lesions were distributed over his face, trunk and limbs, which improved only after discontinuation of imatinib therapy. To the best of our knowledge, this is the first report of imatinib-induced LDE in the Chinese population.

  18. Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma.

    Science.gov (United States)

    Suit, H D; Mankin, H J; Wood, W C; Proppe, K H

    1985-06-01

    The rationale for combining radiation with conservative surgery in the treatment of sarcoma of soft tissue is discussed, as well as the advantages for performing the radiation preoperatively on the one hand and postoperatively on the other. The results of treatment of soft tissue sarcoma by radical resectional surgery or amputation in 464 patients at four centers and by conservative surgery, and postoperative radiation in 416 patients at three centers, have been reviewed. The local failure rates were 18.1% and 18.3%, respectively. The results obtained by radiation administered postoperatively (110 patients) or preoperatively (60 patients) at the Massachusetts General Hospital during the period September 1971 to August 1982 are analyzed and discussed with reference to 5-year actuarial local control and survival results as well as causes of failure with respect to AJC stage, histologic type, anatomic site, and size of tumor. The results which have been obtained by the preoperative approach are judged to be superior, particularly for the larger lesions and higher grades that predominated in that group. Of a total of 170 patients, there were 19 local failures; 13 of these were diagnosed at the time when metastatic disease was not evident. Of those 13, 12 have been subjected to salvage surgery and 7 remain with no evidence of disease at 1 to 3.5 years after the salvage procedure. A major problem in the management of these patients remains the occult metastatic disease.

  19. Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GIST): The EORTC STBSG Experience

    NARCIS (Netherlands)

    Rutkowski, P.; Gronchi, A.; Hohenberger, P.; Bonvalot, S.; Schoffski, P.; Bauer, S.; Fumagalli, E.; Nyckowski, P.; Nguyen, B.P.; Kerst, J.M.; Fiore, M.; Bylina, E.; Hoiczyk, M.; Cats, A.; Casali, P.G.; Cesne, A. le; Treckmann, J.; Stoeckle, E.; Wilt, J.H.W. de; Sleijfer, S.; Tielen, R.; Graaf, W.T. van der; Verhoef, C.; Coevorden, F. van

    2013-01-01

    BACKGROUND: Preoperative imatinib therapy of locally advanced GIST may facilitate resection and decrease morbidity of the procedure. METHODS: We have pooled databases from 10 EORTC STBSG sarcoma centers and analyzed disease-free survival (DFS) and disease-specific survival (DSS) in 161 patients with

  20. Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GIST): The EORTC STBSG Experience.

    NARCIS (Netherlands)

    Rutkowski, P.; Gronchi, A.; Hohenberger, P.; Bonvalot, S.; Schoffski, P.; Bauer, S.; Fumagalli, E.; Nyckowski, P.; Nguyen, B.P.; Kerst, J.M.; Fiore, M.; Bylina, E.; Hoiczyk, M.; Cats, A.; Casali, P.G.; Cesne, A. le; Treckmann, J.; Stoeckle, E.; Wilt, J.H.W. de; Sleijfer, S.; Tielen, R.; Graaf, W.T.A. van der; Verhoef, C.; Coevorden, F. van

    2013-01-01

    BACKGROUND: Preoperative imatinib therapy of locally advanced GIST may facilitate resection and decrease morbidity of the procedure. METHODS: We have pooled databases from 10 EORTC STBSG sarcoma centers and analyzed disease-free survival (DFS) and disease-specific survival (DSS) in 161 patients with

  1. Preoperative lanreotide treatment improves outcome in patients with acromegaly resulting from invasive pituitary macroadenoma.

    Science.gov (United States)

    Li, Z-Q; Quan, Z; Tian, H-L; Cheng, M

    2012-01-01

    To investigate whether 3 months' preoperative treatment with lanreotide improved outcome in newly diagnosed patients with acromegaly resulting from invasive pituitary macroadenoma. After baseline evaluation, untreated patients were randomized to undergo direct transsphenoidal surgery or lanreotide treatment (30 mg via intramuscular injection every 2 weeks, increased to 30 mg/week at week 8 if growth hormone nadir > 2.5 μg/l), for 3 months prior to surgery. Tumour shrinkage following lanreotide treatment was analysed. Cure was evaluated at 3 months postsurgery by measuring growth hormone and insulinlike growth factor-1 (IGF-1) levels. Preoperative lanreotide treatment significantly reduced mean tumour size. Growth hormone and IGF-1 levels were lower in the pretreatment group than in the direct surgery group at 3 months postsurgery. According to combined growth hormone and IGF-1 levels, significantly more patients were cured by trans-sphenoidal surgery in the pretreatment group compared with the direct surgery group (11 of 24 and five of 25 patients, respectively). Lanreotide treatment for 3 months before trans-sphenoidal surgery effectively reduced tumour size, and improved surgical cure rate, in newly diagnosed patients with acromegaly resulting from invasive pituitary macroadenoma.

  2. Treatment of resectable distal rectal cancer with preoperative chemoradiation and sphincter saving surgery

    Directory of Open Access Journals (Sweden)

    Omrani Pour R

    2000-06-01

    Full Text Available To determine if pre-operative combined chemoradiation therapy increase sphincter preservation in the treatment of low-lying rectal cancer, 15 patients were treated with pre-operative chemoradiation: 5FU plus mitomycin C plus 4500-5000 Rad concurrent external beam radiotherapy between Jan 1997 and Jan 1999. There were 10 men and 5 women (Mean age: 49 y with the diagnosis of invasive resectable primary adenocarcinoma of distal rectum limited to pelvis. Median tumor distance from anal verge was 3.3 cm (Range 0-5 cm and half of the patients were absolute candidate for abdominoperineal resection. After 4-6 weeks, all patients were undergone proctectomy and eventually sphincter preservation surgery was done on 9 patients with colonal anastomosis. Function of sphincter was excellent in 6 of them (66% and good in 3 patients (33%. There was no case of incontinence. Complications of surgery were minimal: One case of stricture (10% and one case of partial rupture of anastomosis (10%. Complete pathologic response was achieved on one patient (6.6% and combined pre-operative chemoradiation has changed the plane of surgery from abdominoperineal resection to sphincter saving in 69.2% of patients.

  3. Preoperative analgesia for children and adolescents to reduce pain associated with dental treatment.

    Science.gov (United States)

    McCann, Catherine

    2017-03-01

    Data sourcesCochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, LILACS, ISI Web of Science, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform.Study selectionRandomised controlled clinical trials of analgesics given before dental treatment versus placebo or no analgesics in children and adolescents up to 17 years of age. Children and adolescents having dental treatment under sedation (including nitrous oxide/oxygen) or general anaesthesia were excluded.Data extraction and synthesisTwo reviewers independently selected studies, abstracted data and assessed risk of bias. Standard Cochrane methodological approaches were used.ResultsFive trials involving 190 patients were included. None of the studies were at low risk of bias. Three trials involved dental treatment and two involved orthodontic treatment. Three of the included trials compared paracetamol with placebo. Meta-analysis of the two trials showed no evidence of a benefit in taking paracetamol preoperatively; (RR) for postoperative pain of 0.81 (95%CI; 0.53 to 1.22). Four trials compared ibuprofen with placebo. Pooled data from two studies showed a statistically significant mean difference in severity of postoperative pain of -13.44 (95%CI; -23.01 to -3.88) on a visual analogue scale (0 to 100), which indicated a probable benefit. Both trials were at high risk of bias and the quality of the evidence is low.ConclusionsFrom the available evidence, we cannot determine whether or not preoperative analgesics are of benefit in paediatric dentistry for procedures under local anaesthetic. There is probably a benefit in using preoperative analgesics prior to orthodontic separator placement. The quality of the evidence is low. Further randomised clinical trials should be completed with appropriate sample sizes and well defined outcome measures.

  4. Impact of preoperative patient characteristics on posturethroplasty recurrence: The significance of stricture length and prior treatments

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    Jibril Oyekunle Bello

    2016-01-01

    Full Text Available Introduction: Urethral strictures are common in urologic practice of Sub-Saharan Africa including Nigeria. We determine the rate of stricture recurrence following urethroplasty for anterior urethral strictures and evaluate preoperative variables that predict of stricture recurrence in our practice. Subjects and Methods: Thirty-six men who had urethroplasty for proven anterior urethral stricture disease between February 2012 and January 2015 were retrospectively analyzed. Preoperative factors including age, socioeconomic factors, comorbidities, etiology of strictures, stricture location, stricture length, periurethral spongiofibrosis, and prior stricture treatments were assessed for independent predictors of stricture recurrence. Results: The median age was 49.5 years (range 21-90, median stricture length was 4 cm (range 1-18 cm and the overall recurrence rate was 27.8%. Postinfectious strictures, pan urethral strictures or multiple strictures involving the penile and bulbar urethra were more common. Most patients had penile circular fasciocutaneous flap urethroplasty. Following univariate analysis of potential preoperative predictors of stricture recurrence, stricture length, and prior treatments with dilations or urethrotomies were found to be significantly associated with stricture recurrence. On multivariate analysis, they both remained statistically significant. Patients who had prior treatments had greater odds of having a recurrent stricture (odds ratio 18, 95% confidence interval [CI] 1.4-224.3. Stricture length was dichotomized based on receiver operating characteristic (ROC analysis, and strictures of length ≥5 cm had significantly greater recurrence (area under ROC curve of 0.825, 95% CI 0.690-0.960, P = 0.032. Conclusion: Patients who had prior dilatations or urethrotomies and those with long strictures particularly strictures ≥5 cm have significantly greater odds of developing a recurrence following urethroplasty in Nigerian

  5. Complete haematological response to Imatinib in chronic myeloid ...

    African Journals Online (AJOL)

    Dr Erius

    1Catholic University of Health and Allied Sciences, Mwanza Tanzania ... A few studies have defined patient delays and primary ... Imatinib (Glivec), a very selective ... patients attending care at the Ocean Road Cancer Institute (ORCI) in Dar es ... transfusion history prior to treatment, complete blood count indices, spleen size ...

  6. [The effect of halo-gravity traction in the preoperative treatment of neuromuscular scoliosis].

    Science.gov (United States)

    Flierl, S; Carstens, C

    1997-01-01

    The purpose of this study is to evaluate the influence of halo-gravity-traction on paralytic scoliosis in various neurologic diseases. Between 1980 and 1993 preoperative halo-gravity-traction was applied in 32 patients with paralytic scoliosis (23 patients with myelomeningocele, 6 patients with poliomyelitis, 3 patients with cerebral palsy). In the myelomeningocele group the average curvature before treatment was 97.8 degrees, after surgery 45.1 degrees; which is an improvement of 53.9%. Halo-gravity-traction accounted for 12.8% improvement. In the poliomyelitis group the average curvature before treatment was 104.3 degrees, after surgery 58.0 degrees; which is an improvement of 44.4%. Halo-gravity-traction accounted for 16.9% improvement. In the cerebral palsy group the average curvature before treatment was 75.0 degrees, after surgery 39.0 degrees; which is an improvement of 48.0%. Halo-gravity-traction accounted for -2.7% improvement. If there is an effect the question remains, whether this will have consequences for the surgical outcome. The comparison between good and bad responders with the surgical result shows, that this result is independent of the halo-gravity-traction. From this results we draw the conclusion, that preoperative halo-gravity-traction can not be recommended in paralytic scoliosis.

  7. Preoperative radiotherapy for inoperable stage II endometrial cancer: insights into improving treatment and outcomes.

    Science.gov (United States)

    Lee, Marette H; Aquino-Parsons, Christina; Hoskins, Paul J; Lim, Peter; Kwon, Janice S

    2013-07-01

    To review recurrence patterns and survival outcomes of women receiving preoperative radiotherapy for clinical stage II endometrial cancer in British Columbia. We performed a retrospective population-based cohort study of all patients with clinical stage II endometrial cancer who were referred to the British Columbia Cancer Agency from 2000 to 2008, deemed ineligible for primary surgery, and therefore offered preoperative radiotherapy followed by surgery. Patient demographics, uterine risk factors, timing and details of treatments, and timing and sites of recurrence were obtained from patient records. Primary outcome measures were the sites and rates of recurrence and recurrence-free survival. We identified 29 patients with a mean age of 61 years (range 41 to 83) and median follow-up of 3.1 years (range 0.3 to 5.3). Three-year overall survival was 79%, and median recurrence-free survival was 2.5 years. Eight patients had recurrence of disease (27.6%), with a median time to recurrence of 1.3 years, (range 0.4 to 2.7). Six of these eight women had two or more high-risk uterine factors (deep myometrial invasion, grade 3 tumour), ovarian involvement, or adverse histological type (carcinosarcoma), compared with only one of 21 patients without recurrence. Seven of eight women had recurrence outside the radiated volume of tissue. Median survival after recurrence was 1.0 years (range 0.4 to 2.2). Women with clinical stage II endometrial cancer had a significant risk of recurrence when treated with preoperative radiotherapy followed by surgery. They were more likely to have distant recurrences, implying the need for an alternate treatment paradigm.

  8. Long-term results and complications of preoperative radiation in the treatment of rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reed, W.P.; Garb, J.L.; Park, W.C.; Stark, A.J.; Chabot, J.R.; Friedmann, P.

    1988-02-01

    A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis.

  9. Effect of imatinib on the biochemical parameters of the reproductive function in male Swiss albino mice

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    A M Prasad

    2011-01-01

    Full Text Available Background: Treatment of cancers with cytotoxic agents such as tyrosine kinase inhibiting drugs often, but not always, result in transient to permanent testicular dysfunction. Germ cells are important targets of many chemicals. Most of the drugs are genotoxins and induce irreversible effect on genetic makeup. These mutagenic changes are proportionally related to carcinogenesis. This is alarmingly dangerous in youth and children, since these effects last longer, affecting fertility or forming basis for carcinogenesis. There is paucity of reports on planned studies of imatinib on the testicular function. Hence, the study was planned to assess the effects of imatinib on biochemical markers of testicular functions in male Swiss albino mice. Materials and Methods: Male Swiss albino mice were treated with imatinib and sacrificed at the end of first, second, fourth, fifth, seventh, and tenth week after the last exposure to imatinib. The testis were removed, weighed, and processed for biochemical analysis. Results: The intratesticular testosterone level was significantly (P<0.001 reduced in treated groups and severe effect was observed on week 4 and 5. The intratesticular lactate dehydrogenase (LDH level was significantly increased by imatinib in all treated groups up to week 5. Conclusion: Imatinib does affect testosterone and LDH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with imatinib for gastrointestinal tumors and chronic myeloid leukemia.

  10. Helical Tomotherapy Combined with Capecitabine in the Preoperative Treatment of Locally Advanced Rectal Cancer

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    Ming-Yii Huang

    2014-01-01

    Full Text Available The aim of this study was to evaluate the efficacy of helical tomotherapy plus capecitabine as a preoperative chemoradiotherapy (CRT in patients with locally advanced rectal cancer (LARC. Thirty-six LARC patients receiving preoperative CRT were analyzed. Radiotherapy (RT consisted of 45 Gy to the regional lymph nodes and simultaneous-integrated boost (SIB 50.4 Gy to the tumor, 5 days/week for 5 weeks. Chemotherapy consisted of capecitabine 850 mg/m2, twice daily, during the RT days. Patients underwent surgery 6–8 weeks after completion of CRT. Information was collected for patient characteristics, treatment response, and acute and late toxicities. Grade 3/4 (G3+ toxicities occurred in 11.1% of patients (4/36. Sphincter preservation rate was 85.2% (23/27. Five patients (14.3% achieved pathological complete response. Tumor, nodal, and ypT0-2N0 downstaging were noted in 60% (21/35, 69.6% (16/23, and 57.1% (20/35. Tumor regression grade 2~4 was achieved in 28 patients (80%. After a median follow-up time of 35 months, the most common G3+ late morbidity was ileus and fistula (5.7%, 2/35. The study showed that capecitabine plus helical tomotherapy with an SIB is feasible in treatment of LARC. The treatment modality can achieve a very encouraging sphincter preservation rate and a favorable ypT0-2N0 downstaging rate without excessive toxicity.

  11. Effects of preoperative bromocriptine treatment on prolactin-secreting pituitary adenoma surgery

    Science.gov (United States)

    CAO, YINGXIAO; WANG, FENGJU; LIU, ZHENBO; JIAO, BAOHUA

    2016-01-01

    Pituitary adenomas are benign intracranial endocrine tumors, accounting for ~10% of intracranial tumors. The aim of the present study was to analyze the effects of preoperative treatment with bromocriptine on the surgical treatment and postoperative complications of prolactin-secreting pituitary adenomas (prolactinomas). Data from 102 patients whose prolactinomas were surgically treated between March 2006 and March 2010 were retrospectively reviewed in the present study. The study group included 54 patients who had been treated preoperatively with bromocriptine. The patients were examined by magnetic resonance imaging (MRI) of the head and coronal computed tomography (CT) scanning, after which the pathological diagnosis of prolactinoma was confirmed. A total of 64 patients underwent total resection surgery through the nose and sphenoid sinus, and 25 patients underwent subtotal resection surgery or excision of a large portion of the tumor, leaving only a small quantity of residual tumor or tumor capsule. Patients were followed up for 1–9 months using MRI and measurements of serum prolactin levels. Seven patients were lost to follow-up. The results of the present study demonstrated that patients who were treated with large doses of bromocriptine or used bromocriptine chronically suffered from an increased rate of surgical difficulties and postoperative complications, as compared with the patents who had not been pre-treated with bromocriptine. In conclusion, oral administration of bromocriptine is important in the treatment of prolactinoma tumors. However, large doses or long-term use of bromocriptine may increase difficulties in surgery or postoperative complications, and reduce its ability to treat prolactinonas, as it can lead to hardening of the tumor tissue and capsules, and aggravate pituitary stalk adhesions. PMID:27168837

  12. Positron emission tomography in patients with aggressive fibromatosis/desmoid tumours undergoing therapy with imatinib

    Energy Technology Data Exchange (ETDEWEB)

    Kasper, Bernd; Hohenberger, Peter [University of Heidelberg, Sarcoma Unit, ITM - Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, Mannheim (Germany); Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G. [German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

    2010-10-15

    We used {sup 18}F-FDG PET to evaluate the FDG uptake in patients with aggressive fibromatosis (AF, also known as desmoid tumours) undergoing therapy with imatinib (imatinib mesylate, Glivec). The pilot study included nine patients with progressive AF receiving oral treatment with imatinib at a daily dose of 800 mg. Patients were examined using PET prior to the start of therapy and during imatinib treatment. Restaging according to the Response Evaluation Criteria in Solid Tumors (RECIST) was performed in parallel using CT and/or MRI and served as reference. The clinical outcomes in nine evaluable patients were as follows: seven patients with stable disease, and two patients with progressive disease. A 27% decrease in the median average standardized uptake value (SUV) of the sequential PET examinations was demonstrated in all evaluable patients with three patients (33%) showing a decrease in SUV of more than 40% (48%, 52% and 54%, respectively); no patient showed a substantial increase in SUV. To our knowledge, this is the first series of AF patients undergoing treatment with imatinib and monitored using sequential PET imaging, that allows detection of SUV changes after imatinib induction, thus helping to decide whether treatment should be continued or not. (orig.)

  13. Combined liver transplantation plus imatinib for unresectable metastases of gastrointestinal stromal tumours.

    Science.gov (United States)

    Serralta, Alfonso S; Sanjuan, Fernando R; Moya, Angel H; Orbis, Francisco C; López-Andújar, Rafael; Pareja, Eugenia I; Vila, Juan C; Rayón, Miguel; Juan, Manuel B; Mir, José P

    2004-11-01

    Therapeutic options for treating unresectable hepatic metastases of leiomyosarcomas were scarce until a few years ago. Recent advances in the study of the biology of intestinal tumours have radically changed our knowledge of their pathogenesis. Many of the tumours previously considered as leiomyosarcomas are now identified as gastrointestinal stromal tumours (GISTs). The introduction of imatinib (an antineoplasic drug that specifically acts on the pathogenesis of these tumours) has shown promising results in patients with advanced GISTs. We present three patients with the initial diagnosis of unresectable hepatic metastases of leiomyosarcomas. They received liver transplants. All three had tumour recurrences after transplantation. Histological re-evaluation identified a stromal origin of the tumours, and the patients were treated with imatinib therapy (400 mg/day). Recurrence occurred in all patients after a mean of 38.3 months, but imatinib treatment achieved control of the tumours. The current survival times with the combination of transplantation and imatinib are 92, 48 and 46 months for the three patients. This series is small and inconclusive, but imatinib treatment showed promising results. The treatment options for patients with unresectable metastases of GISTs must be defined, as in these three patients liver transplantation achieved a disease-free status but all had tumour recurrences before starting the imatinib treatment.

  14. Preoperative Concurrent Radiochemotherapy for Locally Advanced Esophageal Cancer: Treatment Outcome and Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Young; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhing Ook; Shim, Young Mog; Im, Young Hyuck [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2007-09-15

    Purpose: This study reports the results of the use of preoperative concurrent radiochemotherapy (CRCT) for the treatment of locoregionally advanced esophageal cancer. Materials and Methods: From 1998 through 2005, 61 patients with intrathoracic esophageal cancer at stages II-IVB (without distant organ metastasis and presumed to be respectable) received preoperative CRCT. CRCT consisted of radiotherapy (45 Gy /25 fractions /5 weeks) and FP chemotherapy (5-FU 1 g/m2/day, days 1-4 and 29-32, Cisplatin 60 mg/m2/day, days 1 and 29). An esophagectomy was planned in 4 {approx} 6 weeks after the completion of CRCT. Results: There were two treatment-related deaths. Among the 61 patients, 53 patients underwent surgery and 17 patients achieved a pathological complete response (pCR). The overall survival (OS) rates of all 61 patients at 2 and 5 years were 59.0% and 38.0%, respectively. The rates of OS and disease-free survival (DFS) of the surgically resected patients at 2 and 5 years were 61.6%, 40.1% and 53.3%, 41.8%, respectively. By univariate analysis, achievement of pCR and a clinically uninvolved distant lymph node (cM0) were favorable prognostic factors for OS and DFS. There were 27 patients that experienced a relapse-a locoregional relapse occurred in 5 patients, a distant metastasis occurred in 12 patients and combined failure occurred in 10 patients. Conclusion: The results of the current study are favorable. pCR and an uninvolved distant lymph node were found to be favorable prognostic factors.

  15. 达沙替尼治疗伊马替尼耐药的 BCR/ABL阳性白血病%Dasatinib in treatment of imatinib-resistant BCR/ABL positive leukemia

    Institute of Scientific and Technical Information of China (English)

    严红; 赵海军

    2014-01-01

    This study was aimed to evaluate the efficacy and safety of dasatinib in BCR /ABL positive leukemia patients with resistance to imatinib.Method 9 patients with imatinib -resistant chronic myelogenous leukemia ( CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph+ALL) received 100~140 mg· d-1 dasatinib orally.Their overall survival and tolerance were evalua-ted.Results After the dasatinib treatment ,2 patients with CML in chronic phase achieved complete hematologic response ( CHR) ,one of them achieved complete cytogenetic response (CCyR);4 of 5 patients with CML in blast crisis achieved CHR and partly cytogenetic response (PCyR);one patient had no response .Treated with dasatinib,one patient with Ph +ALL,presented with E255V mutation,a-chieved CHR and PCyR .The other died of infection .Conlusion Receiving therapy of dasatinib , patients with resistance to imatinib could achieve CHR ,even PCyR .%目的:评价达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病的疗效和安全性。方法对9例伊马替尼耐药的慢性髓系白血病( CML)或Ph阳性急性淋巴细胞白血病( Ph+ALL)患者,给予达沙替尼100~140 mg· d-1口服治疗,评估疗效和耐受情况。结果9例伊马替尼耐药的BCR/ABL阳性白血病,2例CML-CP患者均获得CHR,1例达CCyR;5例CML-BC患者中4例获得CHR和PCyR,1例NR;2例Ph+ALL患者中1例检测到E255V突变,采用达沙替尼治疗达CHR和PCyR,1例诱导缓解时,同时行VDP方案化疗,继发严重感染死亡。结论达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病患者可获得血液学甚至细胞遗传学缓解,且耐受性好。

  16. 甲磺酸伊马替尼治疗慢性粒细胞白血病疗效观察%Efficacy of imatinib in the treatment of chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    黄敬青

    2009-01-01

    目的 探讨甲磺酸伊马替尼治疗慢性粒细胞白血病(CML)的体会.方法 40例CML患者接受甲磺酸伊马替尼治疗,其中慢性期(CP)20例,加速期(AP)8例,急变期(BC)12例.甲磺酸伊马替尼用法:CP患者400 mg/d,AP和BC患者600 mg/d,均为餐后1次顿服.治疗前全面查体,查血象、骨髓象、Ph染色体和(或)bcr/abl融合基因.治疗期间第1个月每周查血象2次,1个月后每周或2周1次.每2~4周查一次肝、肾功能.待血液学取得完全缓解(CR)后择期复查骨髓、Ph染色体和(或)bcr/abl基因.根据血象和患者对药物耐受情况及时调整药物剂量.结果 经中位时间20个月(12~24个月)随访,20例CML CP期患者均取得血液学CR,其中7例(35%)Ph染色体转阴,8例AP患者中6例(75%)回到CP,12例BC患者中4例(33.3%)回到CP.药物不良反应有造血功能抑制、眶周和下肢轻度水肿、全身肌肉关节酸痛和恶心、呕吐、低热(37.5~38.5℃)、皮疹、胆红素升高等.结论 甲磺酸伊马替尼对CML有较好疗效,药物不良反应可耐受.%Objective To explore the management experience of imatinib in the treatment of chronic myeloid leuke-mia (CML). Methods There were 40 CML. 20 patients in chronic phase(CP), 8 patients in accelerated phase(AP) and 12 patients in blast crisis(BC). The dosage of imatinib was 400 mg/d for CP patients and 600 mg/d for AP and BC patients. The prescribed dose was administrated orally, once daily after a meal with a large glass of water. Before starting the imatinib administration, all the patients had thorough physical examination as well as blood and bone marrow examination. Ph chromo-some and or the bcr/abl fusion- gene detection again when they achieved a hematological response(CR). Dose was adjusted from time to time according to the results of blood examination and the patients tolerance to the drug. Results After a median 20 - month period of follow - up, all the 20 CP patients achieved complete

  17. Soft-laser use in the preoperative preparation and postoperative treatment of the patients with chronic lung abscesses

    Science.gov (United States)

    Ledin, A. O.; Dobkin, V. G.; Sadov, A. Y.; Galichev, K. V.; Rzeutsky, V. S.

    1999-07-01

    We counted expedient to include different methods of the soft-laser use in the preoperative medicinal program and in the postoperative period. During the preoperative preparation the basic group patients together with standard treatment received the combined soft-laser therapy, which included intravenous laser blood irradiation (ILBI) by He-Ve laser and external transcutaneous irradiation of the abscess projection by semi-conductorial arrenite-gallium laser. During postoperative treatment with ILBI remarkable changes were observed in the functional activity of the T- and B- cell. The soft-laser use allowed to achieve improvement of quality and shortening of terms of the preoperative preparation of 1,4 times, to level the immunosuppressive influence of surgery to reduce amount of the postoperative complications in 1,8 times and duration of the postoperative period in 1,5 times.

  18. Rescue pre-operative treatment with Lugol’s solution in uncontrolled Graves’ disease

    Science.gov (United States)

    Falhammar, Henrik

    2017-01-01

    Background Graves’ disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol’s solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported. Methods All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005–2015 and treated with Lugol’s solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency. Results Twenty-seven patients were included. Lugol’s solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5–9 days of iodine therapy (free T4 53–20 pmol/L, P = 0.0002; free T3 20–6.5 pmol/L, P = 0.04; heart rate 87–76 beats/min P = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n = 2, rash and vomiting n = 1, swelling of fingers n = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications. Conclusion Treatment of uncontrolled hyperthyroidism with Lugol’s solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol’s solution could be recommended pre-operatively in Graves’ disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred. PMID:28325735

  19. Differential expression and alternative splicing of cell cycle genes in imatinib-treated K562 cells.

    Science.gov (United States)

    Liu, Jing; Lin, Jin; Huang, Lin-Feng; Huang, Bo; Xu, Yan-Mei; Li, Jing; Wang, Yan; Zhang, Jing; Yang, Wei-Ming; Min, Qing-Hua; Wang, Xiao-Zhong

    2015-09-01

    Cancer progression often involves the disorder of the cell cycle, and a number of effective chemotherapeutic drugs have been shown to induce cell cycle arrest. The purpose of this study was to comprehensively investigate the effects of imatinib on the expression profile of cell cycle genes in the chronic myeloid leukemia (CML) K562 cell line. In addition, we also investigated alternative splicing of the cell cycle genes affected by imatinib, since an important relationship has been shown to exist between RNA splicing and cell cycle progression. Exon array analysis was performed using total RNA purified from normal and imatinib-treated K562 cells. We identified 185 differentially expressed genes and 277 alternative splicing events between the two cell groups. A detailed analysis by reverse transcription-PCR (RT-PCR) of key genes confirmed the experimental results of the exon array. These results suggested that treatment of K562 cells with imatinib shifts the expression and alternative splicing profiles of several cell cycle-related genes. Importantly, these findings may help improve imatinib treatment strategies in patients with CML and may be useful for imatinib resistance research and CML drug development.

  20. Bioequivalence study of two imatinib formulations after single-dose administration in healthy Korean male volunteers.

    Science.gov (United States)

    Jung, J A; Kim, N; Yang, J-S; Kim, T-e; Kim, J-R; Song, G-S; Kim, H; Ko, J W; Huh, W

    2014-12-01

    Imatinib mesylate is effective for chronic myeloid leukaemia and gastrointestinal tumours. We aimed to evaluate the pharmacokinetics of a 200-mg imatinib tablet compared to 2×100-mg imatinib tablets in order to meet the regulatory requirements for marketing in Korea.An open-label, randomized, single-dose, 2-period, 2-treatment cross-over study was conducted in 28 healthy Korean male volunteers. Subjects were administered a 200-mg imatinib tablet and 2×100-mg imatinib tablets under a fasting state according to a randomly assigned order with a 2-week wash-out period. Serial blood samples were collected up to 72 h post-dose. The pharmacokinetic parameters were calculated using non-compartmental methods.A total of 28 subjects were enrolled and 23 subjects completed the study. There were no serious adverse events during the study. 23 mild to moderate adverse events were reported (11 events with 200-mg imatinib vs. 12 events with 2×100-mg imatinib) and subjects recovered without sequelae. The Cmax value was 922.8±318.8 μg/L at 3.15 h for 200-mg imatinib tablet, and 986.3±266.0 μg/L at 2.91 h for the 2×100-mg imatinib tablet. The AUClast of 200-mg and 2×100-mg tablets were 13 084.3±39.1 and 14 131.7±3 826.2 h · μg/L, respectively. The geometric mean ratios (90% confidence intervals) for Cmax and AUClast were 0.9121 (0.8188, 1.0161) and 0.9558 (0.8685, 1.0519), respectively.A newly developed 200-mg imatinib tablet was bioequivalent to 2×100-mg imatinib tablets in healthy Korean subjects. A single-dose of either of the 2 formulations was generally well tolerated.

  1. α-Defensin 1-3 And α-Defensin 4 as Predictive Markers of Imatinib Resistance and Relapse in CML Patients

    Directory of Open Access Journals (Sweden)

    Gabriel Etienne

    2011-01-01

    Full Text Available Objective: Imatinib mesylate is a tyrosine kinase inhibitor used as first line treatment in chronic myeloid leukaemia. Despite a remarkable effectiveness, treatment failure cases have been reported in 20 percent of CML patients. The identification of biomarkers which can predict the response to imatinib is our point of interest.

  2. Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor patients

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Ji-Fang Gong; Jie Li; Jing Gao; Nai-Ping Sun; Lin Shen

    2012-01-01

    AIM:To investigate the efficacy and safety of imatinib dose escalation in Chinese patients with advanced gastrointestinal stromal tumor (GIST).METHODS:Advanced GIST patients previously failing 400 mg imatinib treatment were enrolled in this study.Patients received imatinib with dose escalation to 600mg/d,and further dose escalation to 800 mg/d if imatinib 600 mg/d failed.Progression-free survival,overall survival,clinical efficacy,c-kit/PDGFRA genotype and safety were evaluated.RESULTS:52 patients were enrolled in this study.For the 47 evaluable patients receiving imatinib (600 mg/d),the disease control rate was 40.4%,and the median progression-free survival for all patients was 17 wk (95% CI:3.9-30.1).The median overall survival after dose escalation was 81 wk (95% CI:36.2-125.8).Adverse events,mainly edema,fatigue,granulocytopenia and skin rash were tolerable.However,further dose escalation (800 mg/d) in 14 cases was ineffective,with disease progression and severe adverse events.Among 30 cases examined for gene mutations,patients with exon 9 mutations experienced a better progression-free survival of 47 wk.CONCLUSION:Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit.

  3. Patient-, treatment-, and facility-level structural characteristics associated with the receipt of preoperative lower extremity amputation rehabilitation.

    Science.gov (United States)

    Bates, Barbara E; Hallenbeck, Richard; Ferrario, Toni; Kwong, Pui L; Kurichi, Jibby E; Stineman, Margaret G; Xie, Dawei

    2013-01-01

    To determine patient, treatment, or facility characteristics that influence decisions to initiate a rehabilitation assessment before transtibial or transfemoral amputation within the Veterans Affairs (VA) health care system. Retrospective database study. VA medical centers. A total of 4226 veterans with lower extremity amputations discharged from a VA medical center between October 1, 2002, and September 30, 2004. Evidence of a preoperative rehabilitation assessment after the index surgical stay admission but before the surgical date. Evidence was found that 343 of 4226 veterans (8.12%) with lower extremity amputations received preoperative rehabilitation assessments. Veterans receiving preoperative rehabilitation were more likely to be older, admitted from home, or transferred from another hospital. Patients who underwent surgical amputation at smaller-sized hospitals or in the South Central or Mountain Pacific regions were more likely to receive preoperative rehabilitation compared with patients in mid-sized hospitals or in the Northeast, Southeast, or Midwest regions. Patients with evidence of paralysis, patients treated in facilities with programs accredited by the Commission on Accreditation of Rehabilitation Facilities (P facility-level structural characteristics, we found that older patients were more likely to receive preoperative rehabilitation services (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01-1.02). Patients with a contributing amputation etiology of a previous amputation complication were more likely to receive preoperative consultation rehabilitation services (OR 1.50, 95% CI 1.02-2.19) compared with patients who did not have this etiology. Compared with patients treated in the Southeast region of the United States, those treated in the South Central region (OR 2.52, 95% CI 1.82-3.48) or Mountain Pacific region (OR 1.62, 95% CI 1.11-2.37) were more likely to receive preoperative consultation rehabilitation services. Patients with

  4. An evaluation of preoperative ibuprofen for treatment of pain associated with orthodontic separator placement.

    Science.gov (United States)

    Steen Law, S L; Southard, K A; Law, A S; Logan, H L; Jakobsen, J R

    2000-12-01

    Patients undergoing orthodontic treatment can experience significant levels of pain. This study assessed the effectiveness of preoperative ibuprofen in reducing the incidence and the severity of pain after orthodontic separator placement. Sixty-three adolescent patients (mean age, 13 years) were included in this randomized, double-blind, placebo-controlled, prospective study. Patients were randomly assigned to 1 of 3 experimental conditions: (1) 400 mg of ibuprofen taken orally 1 hour before separator placement and a lactose placebo taken orally immediately after the appointment, (2) a lactose placebo taken orally 1 hour before separator placement and 400 mg of ibuprofen taken orally immediately after the appointment, or (3) a lactose placebo taken orally 1 hour before separator placement and again immediately after the appointment. The patient's level of discomfort was assessed with a visual analog scale at 2, 6, and 24 hours, as well as at 2, 3, and 7 days after placement of the orthodontic separators. An analysis of variance and Duncan's multiple range test revealed that 2 hours after their orthodontic appointment the patients who had taken ibuprofen 1 hour before separator placement had significantly less pain with chewing than did the patients who received either ibuprofen postoperatively or a placebo. Additional measures suggest a trend for less pain for this group of patients. These results support the use of pretreatment ibuprofen for patients requiring analgesics for orthodontic discomfort. Future study of the use of preemptive analgesics in orthodontics is warranted.

  5. Preoperative assessment and treatment of appendiceal mucocele complicated by acute torsion: a case report.

    Science.gov (United States)

    Stark, Christoffer; Jousi, Mikko; Enholm, Berndt

    2014-01-02

    Mucus-producing tumours of the appendix or mucoceles can, if left untreated, lead to dissemination of its contents into the peritoneal cavity causing substantial morbidity to the patient. Symptoms for complicated mucoceles can mimic those of acute appendicitis and the final diagnosis is most likely made intraoperatively. We here present a case that is, to our knowledge, one of only ten described in the literature and the first to characterize torsion of an appendiceal mucocele with abdominal magnetic resonance imaging. The patient, a 34-year-old Caucasian female presented at the emergency department with acute abdominal pain in the right lower quadrant. Initial diagnostic work-up including ultrasonography and abdominal magnetic resonance imaging showed a large tubular mass at the base of the appendix with indirect signs of torsion. A laparoscopic appendectomy was performed the following day where the finding was confirmed. The patient went on to have an uneventful recovery and was discharged from the hospital on the first postoperative day. Magnetic resonance imaging is a useful tool in identifying unknown lesions of the appendix and should be considered the primary imaging modality in especially younger patients requiring diagnostic imaging. In this case the preoperative imaging findings aided in choosing the correct timing and treatment option for the patient.

  6. Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Ratosa Ivica

    2015-06-01

    Full Text Available Background. To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ cancer treated at a single institution.

  7. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).

    Science.gov (United States)

    Wassmann, Barbara; Pfeifer, Heike; Stadler, Michael; Bornhaüser, Martin; Bug, Gesine; Scheuring, Urban J; Brück, Patrick; Stelljes, Matthias; Schwerdtfeger, Rainer; Basara, Nadezda; Perz, Jolanta; Bunjes, Donald; Ledderose, Georg; Mahlberg, Rolf; Binckebanck, Anja; Gschaidmeier, Harald; Hoelzer, Dieter; Ottmann, Oliver G

    2005-07-15

    In adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), minimal residual disease (MRD) after stem cell transplantation (SCT) is associated with a relapse probability exceeding 90%. Starting imatinib in the setting of MRD may decrease this high relapse rate. In this prospective multicenter study, 27 Ph+ ALL patients received imatinib upon detection of MRD after SCT. Bcr-abl transcripts became undetectable in 14 (52%) of 27 patients, after a median of 1.5 months (0.9-3.7 months) ((early)CR(mol)). All patients who achieved an (early)CR(mol) remained in remission for the duration of imatinib treatment; 3 patients relapsed after imatinib was discontinued. Failure to achieve polymerase chain reaction (PCR) negativity shortly after starting imatinib predicted relapse, which occurred in 12 (92%) of 13 patients after a median of 3 months. Disease-free survival (DFS) in (early)CR(mol) patients is 91% +/- 9% and 54% +/- 21% after 12 and 24 months, respectively, compared with 8% +/- 7% after 12 months in patients remaining MRD+ (P < .001). In conclusion, approximately half of patients with Ph+ ALL receiving imatinib for MRD positivity after SCT experience prolonged DFS, which can be anticipated by the rapid achievement of a molecular complete remission (CR). Continued detection of bcr-abl transcripts after 2 to 3 months on imatinib identifies patients who will ultimately experience relapse and in whom additional or alternative antileukemic treatment should be initiated.

  8. Imatinib Mesylate Exerts Anti-Proliferative Effects on Osteosarcoma Cells and Inhibits the Tumour Growth in Immunocompetent Murine Models

    Science.gov (United States)

    Ory, Benjamin; Charrier, Céline; Brion, Régis; Blanchard, Frederic; Redini, Françoise; Heymann, Dominique

    2014-01-01

    Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1). Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma) and POS-1 (undifferentiated osteosarcoma). Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R), appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor status of patients

  9. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  10. O tratamento da Leucemia Mielóide Crônica com mesilato de imatinibe Therapy of Chronic Myeloid Leukemia with imatinib mesylate

    Directory of Open Access Journals (Sweden)

    Vaneuza M. Funke

    2008-04-01

    Full Text Available O mesilato de imatinibe é atualmente o tratamento de escolha para pacientes com Leucemia mielóide Crônica (LMC recém-diagnosticados. Desde os primeiros estudos clínicos em 1998 até o estudo IRIS, que comparou o uso em primeira linha de imatinibe com interferon + ara-C, esta droga vem se consolidando em segurança e eficácia. Ainda há, entretanto questionamentos sobre a melhor dose inicial, a identificação dos pacientes que mais se beneficiariam e a melhor abordagem frente a respostas sub-ótimas e resistência. Os principais estudos clínicos publicados com mesilato de imatinibe são revisados no presente artigo, e discutidos sob a perspectiva da realidade brasileira.Imatinib mesylate is currently the gold-standard therapy for patients with newly diagnosed Chronic Myelogenous Leukemia. From the clinical trials in 1998 to the IRIS study, which compared first line imatinib treatment with interferon and low dose ara-C, this drug has been consolidated in regards to its safety and efficacy. There are still some questions to answer. Which would be the best initial dose? Are there any patients who benefit more than others? What is the best approach to suboptimal response and resistance? The most important published clinical studies are reviewed in the current article and discussed from a Brazilian perspective.

  11. Clinical relative factors analysis of imatinib on treatment of chronic myeloid leukemia%伊马替尼治疗慢性髓系白血病临床疗效的相关影响因素分析

    Institute of Scientific and Technical Information of China (English)

    陈莹莹; 曾庆曙; 杨明珍; 王永庆; 夏海龙; 江慧敏; 安福润

    2014-01-01

    Objective To analyse the relationship between the clinical efficacy of imatinib treatment on chronic myeloid leukemia in chronic phaseand risk stratification. Methods 98 imatinib-treated patients were enrolled, and before taking imatinib Sokal and Hasford score were used to assess risk stratification to compare if it has statistical significance between different groups. Results In the 98 cases, 89 cases (97.8%) achieved complete hematologic remission(CHR),76 cases(86.4%) achieved partial cytogenetic remission(PCyR) after three months, 63 cases (82.9%) achieved complete cytogenetic response(CCyR) after six months and 24 cases(54.5%) achieved major molecular response ( MMR ) after twelve months. Risk stratification was assessed according to Sokal score. After three months the rate of groups at low, intermediate and high risk categories which achieved PCyR were 94.4%, 82.6% and 66.7%, respectively(P=0.104), after six months the rate of different groups which achieved CCyR were 88.2%,76.9% and 100%, respectively(P=0.319), and after twelve months the rate of different groups at low and intermediate risk categories which achieved MMR were 52.4% and 65.0%( P=0.412 ).According to the patients' condition, before taking imatinib,46 patients were stratified by Hasford, among which 21 at low risk cate-gorie,23 at intermediate risk categorie and 2 at high risk categorie.After three months the rate of groups at low, in-termediate and high risk categories which achieved PCyR were 90.5%, 91.3% and 50%, respectively ( P =0.191),after six months the rate of different groups which achieved CCyR were 83.3%,94.4% and 100%,respec-tively(P=0.528),and after twelve months the rate of different groups at low and intermediate risk categories which achieved MMR were 45.5% and 58.3% ( P=0.842 ) . Conclusion Imatinib mesylate treatment of chronic mye-loid leukemia is good. Patients belonged to low and intermediate risk groups are more likely to get better clinical ef-ficacy than the high

  12. Clinical Observation of Domestic Imatinib Mesylate Tablet in the Treatment of Chronic Myeloid Leukemia%国产甲磺酸伊马替尼片治疗慢性粒细胞白血病的临床观察

    Institute of Scientific and Technical Information of China (English)

    祝文娟; 尹大伟; 李琚; 江娟

    2016-01-01

    OBJECTIVE:To observe therapeutic efficacy and safety of domestic Imatinib mesylate tablet in the treatment of chronic myeloid leukemia(CML). METHODS:16 CML patients were selected,including 7 newly diagnosed CML patients and 9 patients diagnosed as CML more than 12 months. Imatinib mesylate tablet 400 mg,qd were used in all patients. Blood routine, bone marrow cytology,ph chromosome Evaluate efficacy,and observed peripheral blood fusion gene,Bcr-Abl/Abl gene mutation and ADR were all detected. RESULTS:After treatment,16 patients achieved complete hematologic remission (CHR);12 cases were pavtial cytogenetic response(MCyR),of which 2 cases achieved complete cytogenetic response(CCyR),2 cases were cyto-genelic remission. 15 patients'Bcr-Abl/Abl transcript levels were less than 10%,and only one case was more than 10%. No ADR difficult to tolerate was found in 16 patients. CONCLUSIONS:Domestic Imatinib mesylate tablet shows definite early therapeutic efficacy and high safety.%目的:观察国产甲磺酸伊马替尼片治疗慢性粒细胞白血病(CML)患者的疗效及安全性.方法:选取CML患者16例,其中初诊CML即给予甲磺酸IM治疗者7例,诊断CML超过12个月后再给予甲磺酸IM治疗者9例,所有患者均长期口服甲磺酸伊马替尼片400 mg,qd.治疗后3个月通过检测所有患者血常规、骨髓细胞学、费城染色体(Ph染色体)评估疗效,并观察外周血Bcr-Abl/Abl融合基因突变及不良反应发生情况.结果:治疗后,16例患者均达到完全血液学缓解(CHR);12例患者获得部分细胞遗传学缓解(PCyR),2例患者获得完全细胞遗传学缓解(CCyR),2例患者无细胞遗传学缓解;15例患者Bcr-Abl/Abl转录水平10%.16例患者均未出现难以耐受的不良反应.结论:国产甲磺酸伊马替尼片早期疗效确切,安全性高.

  13. Clinical results of tumor shrinkage and evaluation of quality of life in low rectal carcinoma after preoperative combined treatment

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Osamu; Suganuma, Yasushi; Tamura, Takao; Ohnishi, Kazuyoshi; Nishiue, Takashi; Itoh, Masahiko; Horie, Hiroshi; Sawai, Seiji; Takahashi, Toshio (Kyoto Prefectural Univ. of Medicine (Japan))

    1992-10-01

    To improve the surgical rate and the quality of life (QOL) for patients with advanced low rectal carcinoma, we investigated whether preoperative treatments (irradiation and hyperthermia and 5-fluorouracil (5-FU) suppository, irradiation and hyperthermia, irradiation and 5-FU suppository, irradiation alone and 5-FU suppository alone) were useful. The tumor shrinkage rate after preoperative treatments was highest in the irradiation, hyperthermia and 5-FU suppository group. Pathologically complete regression was observed in the 2 of 18 cases (12%). According to our criteria of histological changes, the irradiation, hyperthermia and 5-FU suppository group showed the greatest effectiveness. The 4 year postoperative survival rate and the 4 year local recurrence rate were 100% and 8% in the irradiation, hyperthermia and 5-FU suppository group and the data suggest that these results were the best of the 5 treatments. After the carcinoma was shrunk after irradiation, hyperthermia and 5-FU suppository, the patients could receive curatively a sphincter-saving operation (super-low anterior resection and transanal rectal resection). The fecal continence of 7 patients after sphincter-saving operations was increased as good by manometric study, defecography and clinical evaluation. In conclusion, our data suggest that the preoperative combined treatment of irradiation, hyperthermia and 5-FU suppository prevents local recurrence and increases the possibility of a sphincter-saving operation for advanced rectal carcinoma. (author).

  14. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Gedde-Dahl, Tobias; Markevärn, Berit

    2011-01-01

    Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remissio...

  15. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Gedde-Dahl, Tobias; Markevärn, Berit;

    2011-01-01

    Biologic and clinical observations suggest that combining imatinib with IFN-a may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission...

  16. Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis.

    Science.gov (United States)

    Cassier, Philippe A; Gelderblom, Hans; Stacchiotti, Silvia; Thomas, David; Maki, Robert G; Kroep, Judith R; van der Graaf, Winette T; Italiano, Antoine; Seddon, Beatrice; Dômont, Julien; Bompas, Emanuelle; Wagner, Andrew J; Blay, Jean-Yves

    2012-03-15

    Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non-neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect. Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi-institutional retrospective study to assess the activity of IM in patients with locally advanced/metastatic PVNS/TGCT. Twenty-nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n = 17; 59%). Two patients had metastatic disease to the lung and/or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason. IM displayed interesting activity in patients with PVNS/TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/TGCT must be balanced against the potential toxicity of chronic drug therapy. Copyright © 2011 American Cancer Society.

  17. Optimal Duration of Imatinib Mesylate Therapy in Metastatic Gastrointestinal Stromal Tumours

    Directory of Open Access Journals (Sweden)

    Ruth Gauden

    2011-04-01

    Full Text Available While current literature provides evidence that imatinib mesylate has significant activity in patients with advanced and metastatic gastrointestinal stromal tumour (GIST, and highlights the potential for the development of anticancer drugs based on specific molecular abnormalities present in cancers, specific recommendations concerning the optimal duration of therapy remain controversial. This case presents the favourable outcome of a patient who originally presented almost 9 years ago with widespread, bulky, metastatic GIST involving the abdomen and pelvis. A sustained, complete response was achieved with imatinib and prompted an interruption in treatment 7 years after initial presentation. The disease reoccurred extensively within 9 months of treatment interruption, but once again rapidly completely responded to the recommencement of imatinib, with that response being now maintained for over 9 months. This report suggests that dramatic and durable responses to imatinib can be achieved in individual cases despite the lack of specific guidelines in the literature with respect to defining how long treatment with imatinib should be continued in the absence of evidence of tumour progression.

  18. Molecular response to imatinib & its correlation with mRNA expression levels of imatinib influx & efflux transporters in patients with chronic myeloid leukaemia in chronic phase

    Directory of Open Access Journals (Sweden)

    Hemant Malhotra

    2015-01-01

    Full Text Available Background & objectives: Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2 in CML patients and to correlate these levels with molecular response. Methods: Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non-responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined. Results: No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05 while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene. Interpretation & conclusions: Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings.

  19. Predicting local recurrence following breast-conserving treatment: parenchymal signal enhancement ratio (SER) around the tumor on preoperative MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Cho, Nariya; Koo, Hye Ryoung; Yun, Bo La; Bae, Min Sun; Moon, Woo Kyung [Dept. of Radiology, Seoul National Univ. Coll. of Medicine, Seoul National Univ. Hospital, Seoul (Korea, Republic of)], e-mail: river7774@gmail.com; Chie, Eui Kyu [Dept. of Radiation Oncology, Seoul National Univ. Coll. of Medicine, Seoul National Univ. Hospital, Seoul (Korea, Republic of)

    2013-09-15

    Background: The level of background parenchymal enhancement around tumor is known to be associated with breast cancer risk. However, there is no study investigating predictive power of parenchymal signal enhancement ratio (SER) around tumor for ipsilateral breast tumor recurrence (IBTR). Purpose: To investigate whether the breast parenchymal SER around the tumor on preoperative dynamic contrast-enhanced magnetic resonance imaging (MRI) is associated with subsequent IBTR in breast cancer patients who had undergone breast-conserving treatment. Material and Methods: Nineteen consecutive women (mean age, 44 years; range, 34-63 years) with breast cancer who developed IBTR following breast-conserving treatment and 114 control women matched for age, as well as T and N stages were included. We compared the clinicopathologic features of the two groups including nuclear grade, histologic grade, hormonal receptor status, human epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion, negative margin width, use of adjuvant therapy, and parenchymal SER around the tumor on preoperative DCE-MRI. The SER was measured on a slice showing the largest dimension of the tumor. Multivariate conditional logistic regression analysis was used to identify independent factors associated with IBTR. Results: In univariate analysis, ER negativity (odds ratio [OR] = 4.7; P = 0.040), PR negativity (OR = 4.0; P = 0.013), HER-2 positivity (OR = 3.6; P = 0.026), and a parenchymal SER greater than 0.53 (OR = 23.3; P = 0.011) were associated with IBTR. In multivariate analysis, ER negativity (OR = 3.8; P = 0.015) and a parenchymal SER greater than 0.53 (OR = 13.2; P = 0.040) on preoperative MRI were independent factors associated with IBTR. Conclusion: In addition to ER negativity, a higher parenchymal SER on preoperative MRI was an independent factor associated with subsequent IBTR in patients with breast cancer who had undergone breast-conserving treatment.

  20. Place of preoperative treatment of acromegaly with somatostatin analog on surgical outcome: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Francisco Pita-Gutierrez

    Full Text Available CONTEXT: Transsphenoidal neurosurgery is the accepted first-line treatment of acromegaly in the majority of patients. Previous studies addressing preoperative somatostatin analog (SSA treatment and subsequent surgical cure rates are conflicting, reporting either benefits or no significant differences. OBJECTIVE: The aim of this study, based on a meta-analysis of all published reports, was to investigate whether treatment with SSA before surgery improves the surgical outcome of acromegaly. DATA SOURCES: All studies of preoperative treatment of acromegaly with SSA were systematically reviewed up to December 2011. We searched the Medline, Embase, Cochrane and Google Scholar electronic databases. STUDY SELECTION: The primary endpoint was the biochemical postoperative cure rate. We identified 286 studies, out of which 10 studies (3.49% fulfilling the eligibility criteria were selected for analysis; five retrospective studies with a control group, two prospective non-randomized trials, and three prospective controlled trials. The meta-analysis was conducted using the random-effects model. DATA EXTRACTION: Data were extracted from published reports by two independent observers. DATA SYNTHESIS: A borderline effect was detected in the analysis of all of the trials with control groups, with a pooled odds ratio (OR for biochemical cure with SSA treatment of 1.62 (95% CI, 0.93-2.82. In the analysis of the three prospective controlled trials, a statistically significant effect was identified OR: 3.62 (95% CI, 1.88-6.96. CONCLUSIONS: Preoperative treatment with SSA og GH-secreting pituitary adenomas shows a significant improvement on surgical results. This meta-analysis suggests that in centers without optimal results all patients with a GH-secreting pituitary macroadenoma should be treated with a long-acting SSA prior to surgical treatment.

  1. Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

    Science.gov (United States)

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Li, Jin-Lan; Li, Ling-Di; Zhu, Hong-Hu; Lai, Yue-Yun; Lu, Xi-Jing; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2013-09-01

    The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all Plog reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories.

  2. Imatinib

    Science.gov (United States)

    ... blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the ... or cause blurred vision. Do not drive a car or operate machinery until you know how this ...

  3. Surgical treatment of patients with lung cancer and limited lung function: Preoperative assessment, operative mortality and morbidity

    Directory of Open Access Journals (Sweden)

    Subotić Dragan

    2007-01-01

    Full Text Available Introduction: Lung resection in patients with limited lung function is one of the greatest challenges in general thoracic surgery. Objective. The aim of the study was to analyze the pattern of lung function changes after operation, operative morbidity and mortality and to compare them with control group of patients. Method. The study included 34 patients with limited lung function, operated for primary lung cancer in one-year period. All patients underwent preoperative desobstructive treatment. The type of ventilatory disorder was analyzed depending on preoperative radiographic and bronchoscopic aspect. Statistics: chisquare test, t-test. Results. In patients with lobectomy, the mean difference in forced expiratory volume in the first second (FEV1 between preoperative and postoperative values was 16.81%, whilst in the pneumonectomy group this difference was 39.51%. The mean change in forced vital capacity (FVC in the lobectomy and pneumonectomy group was 15.83% and 42.73% respectively. In the control group of 28 patients with lobectomy, the decrease in FVC and FEV1 was 19.9% and 24.18% respectively. In the control group of 28 patients with pneumonectomy, the decrease in FVC and FEV1 was 43.52% and 41.36% respectively. In patients with limited lung function and lobectomy, changes in FEV1 and VC after resection were significantly lower compared to the control group of patients with lobectomy and normal lung function. None of 34 operated patients with borderline lung function died inside 30 postoperative days. In the same period, of a total number of 344 patients without respiratory function impairment, operative mortality was 3.1%. In the analyzed group, operative morbidity was 32.35%. Cardiovascular and respiratory complications in the analyzed and control groups occurred in 14.7% and 6.1% of patients respectively (p>0.05. Conclusion. Surgery should not be excluded in patients with borderline lung function prior to preoperative treatment and

  4. Use of 3-Dimensional Printing for Preoperative Planning in the Treatment of Recurrent Anterior Shoulder Instability

    Science.gov (United States)

    Sheth, Ujash; Theodoropoulos, John; Abouali, Jihad

    2015-01-01

    Recurrent anterior shoulder instability often results from large bony Bankart or Hill-Sachs lesions. Preoperative imaging is essential in guiding our surgical management of patients with these conditions. However, we are often limited to making an attempt to interpret a 3-dimensional (3D) structure using conventional 2-dimensional imaging. In cases in which complex anatomy or bony defects are encountered, this type of imaging is often inadequate. We used 3D printing to produce a solid 3D model of a glenohumeral joint from a young patient with recurrent anterior shoulder instability and complex Bankart and Hill-Sachs lesions. The 3D model from our patient was used in the preoperative planning stages of an arthroscopic Bankart repair and remplissage to determine the depth of the Hill-Sachs lesion and the degree of abduction and external rotation at which the Hill-Sachs lesion engaged. PMID:26759768

  5. Compound list: imatinib, methanesulfonate salt [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available imatinib, methanesulfonate salt IMA 00186 ftp://ftp.biosciencedbc.jp/archive/open-t...ggates/LATEST/Rat/in_vivo/Liver/Single/imatinib%2C_methanesulfonate_salt.Rat.in_vivo.Liver.Single.zip ...

  6. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarty, Twisha; Crane, Christopher H. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mansfield, Paul F. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Briere, Tina M.; Beddar, A. Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  7. Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer.

    Science.gov (United States)

    García-Cabezas, Sonia; Rodríguez-Liñán, Milagrosa; Otero-Romero, Ana M; Bueno-Serrano, Carmen M; Gómez-Barbadillo, José; Palacios-Eito, Amalia

    2016-10-01

    Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein.

    LENUS (Irish Health Repository)

    Elzinga, Baukje M

    2013-06-01

    Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1\\/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl\\/LC3 co-localization in both K562 and CML patient cells. Bcr-Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr-Abl protein levels to those of untreated cells. This ability to down-regulate Bcr-Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib.

  9. Efficacy of Dasatinib in Treatment of Imatinib-Resistant BCR/ABL Positive Leukemia%达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病的临床研究

    Institute of Scientific and Technical Information of China (English)

    朱雨; 潘良琴; 钱思轩; 宋萍; 于慧; 张苏江; 葛峥; 洪鸣; 田甜

    2013-01-01

    imatinib-resistant BCR/ABL positive leukemia cases,with a median follow-up of 54 (3-75) months.After the dasatinib treatment,88.8% of all the 27 cases achived complete hematologic response (CHR),29.6% of them achived major cytogenetic response (mCyR),37% of all achived complete cytogenetic response (CCyR) and 18.5% cases achived major molecular response (MMR).Patients who received dasatinib in progress of disease (CML-AP,CML-BC and bone marrow relapse Ph+ ALL) had a lower CCyR rate than those in stable disease (CML-CP and bone marrow remission Ph + ALL) (P =0.0377),and 3-4 grade adverse events occured more frequently in progress of disease than that in stable disease.Overall survival of the patients who achived CCyR after dasatinib therapy was statistically longer than those who did not achive CCyR (63 m vs 9 m,P =0.0126).The most common grade 3-4 adverse events during dasatinib therapy including hematology events such as thrombocytopenia (51.8%),neutropenia (48.1%),anemia (33.3%),and non-hematologic events such as pleural effusion (18.5 %),pulmonary infection (18.5 %),pericardial effusion (11.1%).The 3-4 grade adverse events occared within 12 months from dasatinib therapy,and were mainly observed in patients with progress of disease.It is concluded that dasatinib is an effective drug in imatinib-resistant BCR/ABL positive leukemia patients,the better curative effect and better tolerance has been observed in patients who received dasatinib in stable disease.

  10. Os desafios no tratamento da Leucemia mielóide crônica na era do mesilato de imatinibe Challenges in current chronic myeloid leukemia therapy of imatinib era

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    Cármino Antônio de Souza

    2004-12-01

    Full Text Available Um progresso dramático no tratamento da LMC foi conquistado com o surgimento do inibidor da tirosina quinase BCR/ABL mesilato de imatinib. O imatinib induz altas taxas de resposta citogenética e molecular. A mobilização e coleta de células progenitoras periféricas para transplante autólogo após terapia com imatinib é possível e recentemente houve ressurgimento do interesse neste procedimento. Os autores discutem o atual e futuro papel do transplante autólogo no tratamento da LMC e as aplicações clínicas deste método. Provavelmente esse procedimento inicialmente será restrito aos pacientes que falharem na terapia com imatinib. Estudos clínicos serão necessários para definir a melhor aplicação desse método.A dramatic progress in treatment of chronic myeloid leukemia (CML has been achieved with the BCR-ABL tyrosine kinase imatinib. Imatinib induces high rates of cytogenetic and even molecular remissions in CML patients. The collection of Ph negative progenitor blood stem cells (PBSC for autologous hematopoietic cell transplantation (AHCT after imatinib treatment is possible and the interest of this procedure has emerged. The authors discuss the current and future role of autologous transplantation in CML therapy and the clinical applications of this method. Methods for additional purging of the graft are also discussed. It is likely that this procedure will be limited initially to patients who have failed imatinib therapy. Clinical trials are necessary to define the best application of this method.

  11. Imatinib resistance mutation analysis: experience from a tertiary oncology center

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    Mallekavu Suresh Babu

    2015-01-01

    Full Text Available Purpose: BCR-ABL kinase domain (KD mutations account for 50-90% of the imatinib resistance observed in patients of CML-chronic phase. In CML-CP patients receiving imatinib first-line, mutation analysis is recommended in case of failure or suboptimal response using European LeukemiaNet (ELN criteria. The present study was carried out at a tertiary oncology centre in south India to assess which mutations accounted for resistance to imatinib among patients of chronic phase CML being treated with imatinib.Methods: This was a retrospective observational study. We analyzed patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure. Direct sequencing of the BCR-ABL transcript by the Sanger method was used for IRMA testing.Results: Out of 120 tested for IRMA, 36 (30% had detectable mutations. We observed a higher frequency of mutations at amino acids T315, F359 and M351T.Conclusions: Among the patients who were tested for imatinib resistance mutation in view of suboptimal responses while on imatinib or imatinib failure, 30% had IRMA +ve mutations. The high incidence of imatinib resistance in present study may be attributed to the fact that our patients were given higher dose of imatinib (600 mg, if they failed to achieve CCyR at 12 months or CHR at 3 months as they could not afford second generation TKIs.

  12. An uneventful pregnancy and delivery, in a case with chronic myeloid leukemia on imatinib.

    Science.gov (United States)

    Martin, Jovita; Ramesh, Anita; Devadasan, Lalitha; Palaniappan; Martin, Jude J

    2011-04-01

    The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 24-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in the chronic phase, who was on treatment with imatinib, which was stopped by 10(th) week of pregnancy. Until, she completed full term of pregnancy she was on hydroxyurea. The use of imatinib did not have adverse effects on the fetus. The patient had a normal vaginal delivery and gave birth to a healthy 2500 g girl at 37 weeks of gestation. We conclude that imatinib in the first trimester of pregnant lady with CML, though has particular concern regarding the potential teratogenic and other adverse effects, has shown evidences of safe conception, pregnancy and delivery in ladies with CML.

  13. An uneventful pregnancy and delivery, in a case with chronic myeloid leukemia on imatinib

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    Jovita Martin

    2011-01-01

    Full Text Available The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 24-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML in the chronic phase, who was on treatment with imatinib, which was stopped by 10 th week of pregnancy. Until, she completed full term of pregnancy she was on hydroxyurea. The use of imatinib did not have adverse effects on the fetus. The patient had a normal vaginal delivery and gave birth to a healthy 2500 g girl at 37 weeks of gestation. We conclude that imatinib in the first trimester of pregnant lady with CML, though has particular concern regarding the potential teratogenic and other adverse effects, has shown evidences of safe conception, pregnancy and delivery in ladies with CML.

  14. Successful pregnancy outcome in a patient of chronic myeloid leukemia on imatinib therapy

    Directory of Open Access Journals (Sweden)

    Manisha Singhal

    2016-03-01

    Full Text Available Pregnancy and cancer is a complex situation. The coincidence chronic myeloid leukemia (CML and pregnancy is an uncommon event, in part because CML occurs mostly in older age group. The management of CML, during pregnancy is a difficult problem because of potential effects of therapy on the mother and foetus. Imatinib, a tyrosine kinase inhibitor induces dramatic hematologic and cytogenetic responses in CML, but it is not recommended for use in pregnancy or if the patient plans to conceive. In literature there are very few reports of successful outcome of pregnancy while on imatinib. In this report we describe a successful pregnancy and labor under treatment with imatinib in a known case of CML. [Int J Reprod Contracept Obstet Gynecol 2016; 5(3.000: 913-915

  15. Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate

    DEFF Research Database (Denmark)

    Rathe, Mathias; Kielsgaard Kristensen, Thomas; Møller, Michael Boe

    2010-01-01

    The FIP1L1-PDGFRA fusion gene is the most frequent genetic aberration in myeloid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1. Affected patients in adult populations are very sensitive to imatinib therapy. Pediatric cases are rare and so far only one case...... of FIP1L1-PDGFRA positive disease has been reported. We report a 2-year-old female with a myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRA. Treatment with imatinib resulted in complete and durable clinical, hematological, and molecular remission within 3 months after starting...

  16. An uneventful pregnancy and delivery, in a case with chronic myeloid leukemia on imatinib

    OpenAIRE

    2011-01-01

    The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 24-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in the chronic phase, who was on treatment with imatinib, which was stopped by 10 th week of pregnancy. Until, she completed full term of pregnancy she was on hydroxyurea. The use of imatinib did not have adverse effects on the fetus. The patient had a normal vaginal de...

  17. Imatinib triggers mesenchymal-like conversion of CML cells associated with increased aggressiveness

    Institute of Scientific and Technical Information of China (English)

    Alexandre Puissant; Yann Chéli; Jill-Patrice Cassuto; Sophie Raynaud; Laurence Legros; Jean-Max Pasquet; Francois-Xavier Mahon; Frédéric Luciano; Patrick Auberger; Maeva Dufies; Nina Fenouille; Issam Ben Sahra; Arnaud Jacquel; Guillaume Robert; Thomas Cluzeau; Marcel Deckert; Mélanie Tichet

    2012-01-01

    Chronic myelogenous leukemia (CML) is a cytogenetic disorder resulting from the expression of p210BCR-ABL Imatinib,an inhibitor of BCR-ABL,has emerged as the leading compound to treat CML patients.Despite encouraging clinical results,resistance to imatinib represents a major drawback for therapy,as a substantial proportion of patients are refractory to this treatment.Recent publications have described the existence of a small cancer cell population with the potential to exhibit the phenotypic switch responsible for chemoresistance.To investigate the existence of such a chemoresistant cellular subpopulation in CML,we used a two-step approach of pulse and continuous selection by imatinib in different CML cell lines that allowed the emergence of a subpopulation of adherent cells (IM-R Adh) displaying an epithelial-mesenchymal transition (EMT)-like phenotype.Overexpression of several EMT markers was observed in this CML subpopulation,as well as in CD34+ CML primary cells from patients who responded poorly to imatinib treatment.In response to imatinib,this CD44high/CD24low IM-R Adh subpopulation exhibited increased adhesion,transmigration and invasion in vitro and in vivo through specific overexpression of the αVβ3 receptor.FAK/Akt pathway activation following integrin β3 (ITGβ3) engagement mediated the migration and invasion of IM-R Adh cells,whereas persistent activation of ERK counteracted BCR-ABL inhibition by imatinib,promoting cell adhesion-mediated resistance.

  18. Imatinib and nilotinib reverse multidrug resistance in cancer cells by inhibiting the efflux activity of the MRP7 (ABCC10.

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    Tong Shen

    Full Text Available BACKGROUND: One of the major mechanisms that could produce resistance to antineoplastic drugs in cancer cells is the ATP binding cassette (ABC transporters. The ABC transporters can significantly decrease the intracellular concentration of antineoplastic drugs by increasing their efflux, thereby lowering the cytotoxic activity of antineoplastic drugs. One of these transporters, the multiple resistant protein 7 (MRP7, ABCC10, has recently been shown to produce resistance to antineoplastic drugs by increasing the efflux of paclitaxel. In this study, we examined the effects of BCR-Abl tyrosine kinase inhibitors imatinib, nilotinib and dasatinib on the activity and expression of MRP7 in HEK293 cells transfected with MRP7, designated HEK-MRP7-2. METHODOLOGY AND/OR PRINCIPAL FINDINGS: We report for the first time that imatinib and nilotinib reversed MRP7-mediated multidrug resistance. Our MTT assay results indicated that MRP7 expression in HEK-MRP7-2 cells was not significantly altered by incubation with 5 microM of imatinib or nilotinib for up to 72 hours. In addition, imatinib and nilotinib (1-5 microM produced a significant concentration-dependent reversal of MRP7-mediated multidrug resistance by enhancing the sensitivity of HEK-MRP7-2 cells to paclitaxel and vincristine. Imatinib and nilotinib, at 5 microM, significantly increased the accumulation of [(3H]-paclitaxel in HEK-MRP7-2 cells. The incubation of the HEK-MRP7-2 cells with imatinib or nilotinib (5 microM also significantly inhibited the efflux of paclitaxel. CONCLUSIONS: Imatinib and nilotinib reverse MRP7-mediated paclitaxel resistance, most likely due to their inhibition of the efflux of paclitaxel via MRP7. These findings suggest that imatinib or nilotinib, in combination with other antineoplastic drugs, may be useful in the treatment of certain resistant cancers.

  19. A phase I study of imatinib mesylate in combination with chlorambucil in previously treated chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Hebb, Jonathan; Assouline, Sarit; Rousseau, Caroline; Desjardins, Pierre; Caplan, Stephen; Egorin, Merrill J; Amrein, Lilian; Aloyz, Raquel; Panasci, Lawrence

    2011-09-01

    The tyrosine kinase inhibitor, imatinib, has the potential to indirectly inhibit DNA repair. This mechanism of action has been shown to mediate sensitization to chlorambucil in chronic lymphocytic leukemia (CLL). To evaluate this effect in vivo, we performed a phase I study of chlorambucil combined with imatinib in relapsed CLL patients. The three dose levels studied included imatinib at 300, 400, or 600 mg/day. Imatinib was given on days 1-10, and chlorambucil (8 mg/m(2) daily) was given on days 3-7 of a 28-day cycle (up to 6 cycles). Eleven patients participated in this study. Low-grade gastrointestinal toxicities were observed in a dose-dependent manner. Forty-five percent of patients responded (two unconfirmed CRs and three PRs). Two responding patients were fludarabine refractory. The in vitro IC(50) of chlorambucil alone or in the presence of 5 μM imatinib in CLL lymphocytes correlated with the decrease in lymphocyte counts on day 15. Imatinib plasma concentrations achieved in patients were in the range of those effective in in vitro sensitization studies. The combination of chlorambucil and imatinib in patients with previously treated CLL was well tolerated and showed evidence of clinical efficacy. Based on our results, we recommend the 400 mg daily dose of imatinib on days 1-10 with 8 mg/m(3) chlorambucil on days 3-7 every 28 days as the phase II dose. This represents the first clinical trial examining the potential synergy between a tyrosine kinase inhibitor and a conventional alkylating agent for the treatment of CLL.

  20. In vitro effects of imatinib on CD34+ cells of patients with chronic myeloid leukemia in the megakaryocytic crisis phase

    Science.gov (United States)

    MENG, FANKAI; ZENG, WEN; HUANG, LIFANG; QIN, SHUANG; MIAO, NINGNING; SUN, HANYING; LI, CHUNRUI

    2014-01-01

    Imatinib is a tailored drug for the treatment of chronic myeloid leukemia (CML), and has substantial activity and a favorable safety profile when used as a single agent in patients with CML in myeloid blast crisis. The megakaryocytic blast crisis in CML occurs rarely and carries a poor prognosis. The aim of the present study was to investigate the effects of imatinib on cluster of differentiation (CD)34+ cells from patients with CML in the megakaryocytic crisis phase. Bone marrow mononuclear cells (BMNCs) were isolated from patients with CML in the megakaryocytic crisis phase. CD34+ cells were selected from BMNCs by positive immunomagnetic column separation. Imatinib significantly induced G1 arrest, reduced the phosphorylation of cyclin-dependent kinase 1 and retinoblastoma proteins and inhibited the proliferation of CD34+ cells from patients with CML in the megakaryocytic crisis phase. Annexin V/propidium iodide and caspase-3 activity showed that imatinib induced apoptosis. Western blot analysis and protein tyrosine kinase activity assays showed that imatinib inhibited BCR-ABL protein tyrosine kinase activity. The in vitro data thus markedly indicate a potential clinical application of imatinib for patients with CML in the megakaryocytic crisis phase. PMID:24527087

  1. In vitro effects of imatinib on CD34(+) cells of patients with chronic myeloid leukemia in the megakaryocytic crisis phase.

    Science.gov (United States)

    Meng, Fankai; Zeng, Wen; Huang, Lifang; Qin, Shuang; Miao, Ningning; Sun, Hanying; Li, Chunrui

    2014-03-01

    Imatinib is a tailored drug for the treatment of chronic myeloid leukemia (CML), and has substantial activity and a favorable safety profile when used as a single agent in patients with CML in myeloid blast crisis. The megakaryocytic blast crisis in CML occurs rarely and carries a poor prognosis. The aim of the present study was to investigate the effects of imatinib on cluster of differentiation (CD)34(+) cells from patients with CML in the megakaryocytic crisis phase. Bone marrow mononuclear cells (BMNCs) were isolated from patients with CML in the megakaryocytic crisis phase. CD34(+) cells were selected from BMNCs by positive immunomagnetic column separation. Imatinib significantly induced G1 arrest, reduced the phosphorylation of cyclin-dependent kinase 1 and retinoblastoma proteins and inhibited the proliferation of CD34(+) cells from patients with CML in the megakaryocytic crisis phase. Annexin V/propidium iodide and caspase-3 activity showed that imatinib induced apoptosis. Western blot analysis and protein tyrosine kinase activity assays showed that imatinib inhibited BCR-ABL protein tyrosine kinase activity. The in vitro data thus markedly indicate a potential clinical application of imatinib for patients with CML in the megakaryocytic crisis phase.

  2. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).

    Science.gov (United States)

    Wassmann, Barbara; Pfeifer, Heike; Goekbuget, Nicola; Beelen, Dietrich W; Beck, Joachim; Stelljes, Matthias; Bornhäuser, Martin; Reichle, Albrecht; Perz, Jolanta; Haas, Rainer; Ganser, Arnold; Schmid, Mathias; Kanz, Lothar; Lenz, Georg; Kaufmann, Martin; Binckebanck, Anja; Brück, Patrick; Reutzel, Regina; Gschaidmeier, Harald; Schwartz, Stefan; Hoelzer, Dieter; Ottmann, Oliver G

    2006-09-01

    The best strategy for incorporating imatinib in front-line treatment of Ph+ acute lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients with newly diagnosed Ph+ ALL in a prospective, multicenter study to investigate sequentially 2 treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P = .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grades III and IV cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared with patients receiving chemotherapy alone. No imatinib-related severe hematologic or nonhematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy.

  3. Preoperative Plasma Fibrinogen Level as a Significant Prognostic Factor in Patients With Localized Renal Cell Carcinoma After Surgical Treatment.

    Science.gov (United States)

    Lee, Hakmin; Lee, Sang Eun; Byun, Seok-Soo; Kim, Hyeon Hoe; Kwak, Cheol; Hong, Sung Kyu

    2016-01-01

    We sought to investigate the association of preoperative fibrinogen levels with clinicopathologic outcomes after surgical treatment of nonmetastatic renal cell carcinoma. We reviewed the records of 1511 patients who had their fibrinogen levels measured preceding surgery. The associations between preoperative fibrinogen level and risk of adverse clinicopathologic outcomes were tested using the multivariate logistic regression and multiple Cox-proportional hazards model, respectively. Based on plasma fibrinogen levels, we stratified the patients into 2 groups with a cut-off value of 328  mg/dL. Kaplan-Meier analysis showed significantly inferior survival outcomes in progression-free (P fibrinogen level (≥328  mg/dL) was significantly related to a higher Fuhrman grade (hazard ratio [HR] 1.374, P = 0.006) and a larger tumor size (≥7  cm) (HR 2.364, P fibrinogen level is a significant predictor for poor disease progression (HR 1.857, P fibrinogen levels were significantly associated with poor pathological features and worse survival outcomes in patients with nonmetastatic renal cell carcinoma after surgical treatment. Further evaluations such as prospective randomized trials are needed to understand the underlying mechanism for these associations.

  4. Cooperative benefit for the combination of rapamycin and imatinib in tuberous sclerosis complex neoplasia

    Directory of Open Access Journals (Sweden)

    Govindarajan Baskaran

    2012-07-01

    Full Text Available Abstract Tuberous sclerosis (TS is a common autosomal-dominant disorder characterized by tumors of the skin, lung, brain, and kidneys. Monotherapy with rapamycin however resulted in partial regression of tumors, implying the involvement of additional pathways. We have previously implicated platelet-derived growth factor-BB in TS-related tumorigenesis, thus providing a rationale for a combination of mTOR/PDGF blockade using rapamycin and imatinib. Here, we test this combination using a well-established preclinical model of cutaneous tumorigenesis in TS, tsc2ang1 cells derived from a skin tumor from a mouse heterozygous for tsc2. Treatment of tsc2ang1 cells with a combination of rapamycin and imatinib led to an inhibition of proliferation compared with either vehicle treatment or treatment with rapamycin or imatinib monotherapy. Combination therapy also led to a decrease in Akt activation. Potent in vivo activity in animal experiments by combination therapy was noted, without toxicity to the animals. Our findings provide a rationale for the combined use of rapamycin and imatinib, both FDA approved drugs, for the treatment of TS.

  5. Potential usefulness of mucin immunohistochemical staining of preoperative pancreatic biopsy or juice cytology specimens in the determination of treatment strategies for intraductal papillary mucinous neoplasm.

    Science.gov (United States)

    Hisaka, Toru; Horiuchi, Hiroyuki; Uchida, Shinji; Ishikawa, Hiroto; Kawahara, Ryuichi; Kawashima, Yusuke; Akashi, Masanori; Mikagi, Kazuhiro; Ishida, Yusuke; Okabe, Yoshinobu; Nakayama, Masamichi; Naito, Yoshiki; Yano, Hirohisa; Taira, Tomoki; Kawahara, Akihiko; Kage, Masayoshi; Kinoshita, Hisafumi; Shirozu, Kazuo

    2013-11-01

    We classified resected intraductal papillary mucinous neoplasms (IPMNs) into four subtypes (gastric, intestinal, pancreatobiliary and oncocytic) according to their morphological features and mucin expression, determined their clinicopathological characteristics and investigated the possibility of preoperatively diagnosing these subtypes. Sixty resected tumors, 4 preoperative tumor biopsies and 10 preoperative pancreatic juice cytology specimens were analyzed. The gastric and intestinal types accounted for the majority of IPMNs. Non-gastric type IPMNs were of high-grade malignancy. Many of the pancreatobiliary-type IPMNs were in an advanced stage and were associated with a poor prognosis. The results of mucin immunohistochemical staining of preoperative biopsy and surgically resected specimens were in agreement with each other, and in close agreement with those for pancreatic juice cytology specimens obtained from 10 patients during endoscopic retrograde cholangiopancreatography (ERCP). The immunostaining of preoperative biopsy specimens and ERCP-obtained pancreatic juice cytology specimens may be useful in the differential diagnosis of gastric and intestinal types of IPMN. If such techniques enable the preoperative diagnosis of IPMN subtypes, their use in combination with conventional preoperative imaging modalities may lead to surgical treatment best suited for the biological characteristics of the four subtypes.

  6. Does imatinib turn recurrent and/or metastasized gastrointestinal stromal tumors into a chronic disease? - single center experience.

    Science.gov (United States)

    Armbrust, Thomas; Sobotta, Michael; Gunawan, Bastian; Füzesi, Laszlo; Langer, Claus; Cameron, Silke; Ramadori, Giuliano

    2009-07-01

    Gastrointestinal stromal tumors (GIST) are mesenchymal tumors of the gastrointestinal tract supposed to arise from the cells of Cajal because of gain-of-function mutations of the tyrosine receptor kinases c-kit or platelet-derived growth factor receptor A. Imatinib selectively inhibits the kinase activity of both receptors. Despite this breakthrough in the treatment of GIST, resistance against imatinib has been reported to be as high as 50% after the first 2 years of treatment. Outcome of 13 consecutive patients with relapsed or metastasized GIST who were treated with imatinib was analyzed. Mean duration of treatment was 53.5 months. Four patients developed progressive disease and died after a mean treatment time of 31 months in spite of increase of imatinib dosages to 800 mg daily. Two patients (23%) developed a progressive disease after 46 months or 52 months of treatment. Two patients had a stable disease and five had a partial response. The overall progression rate was 46%, the mean survival time since primary diagnosis was 85.8 months. From our experience, frequency of resistance development to imatinib may be below that given in the literature (50% after 2 years). Individual treatment in specialized centers may improve compliance.

  7. An ultra-specific and sensitive sandwich ELISA for imatinib using two anti-imatinib antibodies.

    Science.gov (United States)

    Saita, Tetsuya; Yamamoto, Yuta; Hosoya, Kazuhisa; Yamamoto, Yutaro; Kimura, Sakiko; Narisawa, Yutaka; Shin, Masashi

    2017-05-29

    The development of an immunoassay for a low-molecular-weight drug first requires the identification of specific antibodies that do not cross-react with the drug's metabolites. If two antibodies can simultaneously recognize the entire structure of the drug, we can then utilize them to establish an ultra-specific sandwich ELISA, free from interference due to the metabolic products of the drug. This paper reports an ultra-specific and sensitive sandwich ELISA for determination of the tyrosine kinase inhibitor imatinib using two anti-imatinib antibodies. The anti-imatinib antibodies were obtained by two partial structures of imatinib as haptens (2-(5-amino-2-methylanilino)-4-(3-pyridyl)pyrimidine and 4-{(4-methyl-1-piperazinyl)-methyl}-benzoate). Under optimized conditions, this sandwich ELISA shows a linear detection range from 64 pg mL(-1) to 8 ng mL(-1), and a limit of detection of approximately 64 pg mL(-1) for 100-μL samples. The ELISA is specific to imatinib and while there was no cross-reactivity with the major metabolite N-desmethyl-imatinib, slight cross-reactivity was found with metabolite pyridine-N-oxide-imatinib. This assay demonstrated significantly lower cross-reactivity with metabolites than competitive ELISAs. Using this assay, drug levels were easily measured in rat blood after oral administration of imatinib via a single dose of 30 mg kg(-1) or 100 mg kg(-1). The levels in rat serum measured by this ELISA were comparable with those measured by HPLC, and there was a strong correlation between the values determined by the two methods (y = 0.983x + 0.081, R(2) = 0.948). Thus, we have successfully developed the first specific and sensitive sandwich ELISA for imatinib using two anti-imatinib antibodies. This sandwich ELISA will be a valuable tool for therapeutic drug monitoring and pharmacokinetic studies of imatinib. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal

    Full Text Available BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48, all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid

  9. IMATINIB MESYLATE IN THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA: AN EFFICACY AND SAFETY EVALULATION%伊马替尼治疗慢性粒细胞白血病有效性和安全性观察

    Institute of Scientific and Technical Information of China (English)

    雷媚; 赵洪国; 杨颉

    2012-01-01

    目的 观察甲磺酸伊马替尼治疗慢性粒细胞白血病(CML)的有效性与安全性.方法 51例CML病人给予伊马替尼治疗,观察其血液学、细胞遗传学、分子学反应以及不良反应、总生存和疾病进展情况.结果 CML慢性期病人治疗3个月时97.8%(45/46)获得完全血液学缓解;用药1年后,79,4%(27/34)获得完全细胞遗传学缓解,5.9%(2/34)获得部分细胞遗传学缓解,2.9%(1/34)获得次要细胞遗传学缓解,5.9%(2/34)获得微小细胞遗传学缓解,5.9%(2/34)未获得遗传学反应,29.4%(10/34)获得完全分子遗传学缓解;1、2、3年总生存率分别为100.0%、97.0%、91.6%,疾病无进展生存率分别为100.0%、85.3%、73.1%.3例CML加速期病人1例获得完全血液学缓解,1例获得完全细胞遗传学缓解,1例获得部分细胞遗传学缓解.2例CML急变期病人均死亡,总病程分别为9、15个月.结论 伊马替尼治疗CML慢性期病人,完全血液学缓解率和细胞遗传学缓解率高,且不良反应少,但对加速期和急变期病人疗效欠佳.%Objective To assess the efficacy and safety of imatinib mesylate in the treatment of patients with chronic my-elogenous leukemia (CML). Methods Fifty-one CML patients were treated with imatinib. The responses in hematology, cyto-genetics, molecule and adverse reactions, total survival and progression of the disease were observed. Results After three months of therapy, 97. 8% (45/46) of the patients in chronic phase achieved complete hematologic response (CHR)I After one year of medication, 79.4% (27/34) reached complete cytogenetic response, 5. 9% (2/34) achieved partial cytogenetic response, 2. 9% (1/34) obtained minor cytogenetic response, 5. 9% (2/34) got minimal cytogenetic response, 5. 9% (2/34) did not get cytogenetic response, and patients with complete molecular response accounted for 29. 4% (10/34). The total one-, two-and three-year survival rates were 100. 0%, 97. 0%, and 91

  10. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™

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    Martin Henkes

    2008-03-01

    Full Text Available 1Martin Henkes, 2Heiko van der Kuip, 1Walter E Aulitzky12nd Department of Internal Medicine, Oncology and Hematology, Robert Bosch Hospital, Auerbachstr. 110, Stuttgart, Germany; 2Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, Stuttgart, and University of Tuebingen, GermanyAbstract: Treatment options for chronic myeloid leukemia (CML have changed dramatically during the last decades. Interferon-α treatment and stem cell transplantation (SCT clearly improved survival over conventional chemotherapy and offered the possibility of complete and durable responses. With the advent of the small molecule inhibitor imatinib mesylate (Glivec®, GleevecTM targeting the causative Bcr-Abl oncoprotein, the era of molecular cancer therapy began with remarkable success especially in chronic phase patients. Today, imatinib is the first-line treatment for CML. However, imatinib does not appear to be capable to eliminate all leukemia cells in the patients and pre-existing as well as acquired resistance to the drug has been increasingly recognized. To overcome these problems, several strategies involving dose escalation, combinations with other agents, and novel Bcr-Abl inhibitors have been developed.Keywords: CML therapy, imatinib, SCT, novel kinase inhibitors

  11. [Watermelon stomach: Chronic renal failure and/or imatinib?].

    Science.gov (United States)

    Montagnac, Richard; Blaison, Dominique; Brahimi, Saïd; Schendel, Adeline; Levasseur, Thomas; Takin, Romulus

    2015-11-01

    Watermelon stomach or gastric antral vascular ectasia (GAVE) syndrome is an uncommon cause of sometimes severe upper gastro-intestinal bleeding. Essentially based on a pathognomonic endoscopic appearance, its diagnosis may be unrecognised because mistaken with portal hypertensive gastropathy, while treatment of these two entities is different. Its etiopathogeny remains still unclear, even if it is frequently associated with different systemic illnesses as hepatic cirrhosis, autoimmune disorders and chronic renal failure. The mechanism inducing these vascular ectasia may be linked with mechanical stress on submucosal vessels due to antropyloric peristaltic motility dysfunction modulated by neurohormonal vasoactive alterations. Because medical therapies are not very satisfactory, among the endoscopic modalities, argon plasma coagulation seems to be actually the first-line treatment because the most effective and safe. However, surgical antrectomy may be sometimes necessary. Recently GAVE syndrome appeared as a new adverse reaction of imatinib mesylate, one of the tyrosine kinase inhibitors used in chronic myeloid leukemia, and we report here the observation of such a pathology in one patient treated at the same time by haemodialysis and by imatinib mesylate for chronic myeloid leukemia.

  12. Preoperative physical therapy treatment did not influence postoperative pain and disability outcomes in patients undergoing shoulder arthroscopy: a prospective study

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    Valencia C

    2016-07-01

    Full Text Available Carolina Valencia,1 Rogelio A Coronado,2 Corey B Simon,3,4 Thomas W Wright,5 Michael W Moser,5 Kevin W Farmer,5 Steven Z George3,6,7 1Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, IN, 2Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN, 3Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, FL, 4Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville,FL, 5Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL, 6Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL, 7Brooks–PHHP Research Collaboration, Jacksonville, FL, USA Background: There is limited literature investigating preoperative physical therapy (pre-op PT treatment on pain intensity and disability after musculoskeletal surgery. The purposes of the present cohort study were to describe patient characteristics for those who had and did not have pre-op PT treatment and determine whether pre-op PT influenced the length of postoperative physical therapy (post-op PT treatment (number of sessions and 3-month and 6-month postsurgical outcomes, such as pain intensity and disability. Patients and methods: A total of 124 patients (mean age =43 years, 81 males with shoulder pain were observed before and after shoulder arthroscopic surgery. Demographic data, medical history, and validated self-report questionnaires were collected preoperatively and at 3 months and 6 months after surgery. Analysis of variance models were performed to identify differences across measures for patients who had pre-op PT treatment and those who did not and to examine outcome differences at 3 months and 6 months. Alpha was set at the 0.05 level for statistical significance. Results: Males had less participation in pre-op PT than females (P=0.01. In

  13. Histopathological study of the hepatic and renal toxicity associated with the co-administration of imatinib and acetaminophen in a preclinical mouse model.

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    Nassar, Inthisham; Pasupati, Thanikachalam; Judson, John Paul; Segarra, Ignacio

    2010-06-01

    Imatinib, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukaemia (CML) and gastrointestinal stromal tumors (GIST). Several fatal cases have been associated with imatinib hepatotoxicity. Acetaminophen, an over-the-counter analgesic, anti-pyretic drug, which can cause hepatotoxicity, is commonly used in cancer pain management. We assessed renal and hepatic toxicity after imatinib and acetaminophen co-administration in a preclinical model. Four groups of male ICR mice (30-35 g) were fasted overnight and administered either saline solution orally (baseline control), imatinib 100 mg/kg orally (control), acetaminophen 700 mg/kg intraperitoneally (positive control) or co-administered imatinib 100 mg/kg orally and acetaminophen 700 mg/kg intraperitoneally (study group), and sacrificed at 15 min, 30 min, 1 h, 2 h, 4 h and 6 h post-administration (n = 4 per time point). The liver and kidneys were harvested for histopathology assessment. The liver showed reversible cell damage like feathery degeneration, microvesicular fatty change, sinusoidal congestion and pyknosis, when imatinib or acetaminophen were administered separately. The damage increased gradually with time, peaked at 2 h but resolved by 4 h. When both drugs were administered concurrently, the liver showed irreversible damage (cytolysis, karyolysis and karyorrhexis) which did not resolve by 6 h. Very minor renal changes were observed. Acetaminophen and imatinib co-administration increased hepatoxicity which become irreversible, probably due to shared P450 biotransformation pathways and transporters in the liver.

  14. Results of Preoperative Concurrent Chemoradiotherapy for the Treatment of Rectal Cancer

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    Yoon, Mee Sun; Nam, Taek Keun; Kim, Hyeong Rok; Nah, Byung Sik; Chung, Woong Ki; Kim, Young Jin; Ahn, Sung Ja; Song, Ju Young; Jeong, Jae Uk [Chonnam National University College of Medicine, Gwangju (Korea, Republic of)

    2008-12-15

    The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of 1.8-2.0 Gy at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of 43.2-54 Gy (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range 11 -107 months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59

  15. [Effect of tyrosine kinase inhibitor Imatinib mesylate on proliferation, differentiation and apoptosis of Kasumi-1 leukemia cell line].

    Science.gov (United States)

    Wang, Li-Hong; Rao, Qing; Wang, Min; Wang, Jian-Xiang

    2005-08-01

    To explore the effect of Imatinib mesylate on proliferation, differentiation and apoptosis of leukemic Kasumi-1 cells bearing c-kit mutation. Kasumi-1 cells were treated with Imatinib at different concentrations in culture. Cell proliferation was assayed by MTT assay, expressions of c-kit antigen, surface myeloid antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining and agarose gel electrophoresis. Western blot was used to analyze the level of c-kit protein tyrosine phosphorylation. Imatinib treatment caused a time- and dose-dependent inhibition of the cell proliferation, with a 72 h IC50 of 4.45 micromol/L. Imatinib treatment induced a decrease in the mean fluorescence value of c-kit antigen, a progressive decline in S-phase cell fraction and an increase in G0/G1 cells. Treatment with 5.00 micromol/L of imatinib for 72 h induced an increase in expression of myeloid surface protein CD11, CD13 and CD15, and for 24 h induced an increase in early apoptosis cells [from 9.04% to 86.84% (P Kasumi-1 cells which bear a c-kit mutation, induce differentiation, apoptosis and G0/G1 cells accumulation.

  16. Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST receiving imatinib: an active agent only in non progressive patients

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    Duffaud Florence

    2012-09-01

    Full Text Available Abstract Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST receiving imatinib : an active agent only in non progressive patients. Background Imatinib is a standard treatment for advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed in patients with advanced GIST, and is one of the most frequent side effects of imatinib with grade 3–4 anaemia in 10% of patients. Whether EPO treatment is useful in the management of GIST patients receiving imatinib treatment is unknown. Methods A retrospective study of EPO treatment in GIST patients receiving imatinib was undertaken in 4 centres. Thirty four patients received EPO treatment among the 319 GIST patients treated with imatinib in clinical trials or with compassionate use between 2001 and 2003. The efficacy of EPO on the anaemia of patients with GIST treated with imatinib was analyzed. Results There were 18 males and 16 females with a median age of 59 years. Median WHO-PS was 1. Primary tumour sites were mainly gastric (32% and small bowel (29%. Sites of metastases were mainly liver (82% and peritoneum (79%. The median delay between the initiation of imatinib treatment and EPO was 58 days (range 0–553. Median haemoglobin (Hb level prior to EPO was 9 g/dL (range 6,9-11,8 and 11,7 g/dL (range 6,8-14,4 after 2 months. An increase of more than 2 g/dL was observed in 18 (53% of patients. None of the 7 patients who progressed (PD under imatinib treatment (400 mg/day experienced HB response, as compared to 66% (18/27 of the remaining patients (PR + SD (p = 0,002. Primary tumour site, liver metastases, peritoneal metastases, age, gender did not correlate with HB response to EPO. Response to EPO was observed in 2/11 patients receiving high-dose imatinib (800 mg/day vs 16/23 of others. Using logistic regression, only PD before EPO treatment was retained as a predictive factor for EPO response. Conclusion EPO enables to

  17. Lack of non-hematological cross intolerance of dasatinib to imatinib in imatinib-intolerant patients with Philadelphia chromosome positive chronic myeloid leukemia or acute lymphatic leukemia: a retrospective safety analysis.

    Science.gov (United States)

    Kobayashi, Yukio; Sakamaki, Hisashi; Fujisawa, Shin; Ando, Kiyoshi; Yamamoto, Kazuhito; Okada, Masaya; Ishizawa, Kenichi; Nagai, Tadashi; Miyawaki, Syuichi; Motoji, Toshiko; Usui, Noriko; Iida, Shinsuke; Taniwaki, Masafumi; Uoshima, Nobuhiko; Seriu, Taku; Ohno, Ryuzo

    2011-06-01

    The aim of this retrospective study was to evaluate the toxicity profiles of dasatinib in patients with Philadelphia chromosome positive chronic myeloid leukemia (CML) or acute lymphatic leukemia (ALL) who were intolerant to imatinib, and who had been enrolled in our previous clinical trials to evaluate efficacy of dasatinib in patients resistant or tolerant to imatinib therapy. Twenty-four patients with CML and four with ALL were enrolled in the clinical studies to evaluate the efficacy according to the eligibility criteria related to intolerance to imatinib therapy. The toxicities reported during imatinib therapy were non-hematological toxicities in 23 patients and hematological toxicities in six patients. Patients were administered dasatinib 50-70 mg BID or 100 mg QD. Cross intolerance was observed in four patients who showed hematological toxicity after dasatinib treatment. However, it was possible to successfully continue therapy with only temporary interruption. No cross intolerance in non-hematological toxicity was found with the exception of one patient who showed cross intolerance, which did not result in treatment interruption. Dasatinib can be safely administered to imatinib-intolerant CML or Ph-positive ALL patients.

  18. Imatinib enhances functional outcome after spinal cord injury.

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    Mathew B Abrams

    Full Text Available We investigated whether imatinib (Gleevec®, Novartis, a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury.

  19. Effect of Imatinib on the Oogenesis and Pituitary -Ovary Hormonal Axis in Female Wistar Rat

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    Parichehreh Yaghmaei

    2009-01-01

    Full Text Available Background: Imatinib mesylate, a small-molecular analog of adenosine triphosphate (ATPthat potently inhibits tyrosine kinase activities of Bcr–Abl, PDGFR-β, PDGFR-α, c-Fms, Argand c-kit, is one of the novel molecularly targeted drugs being introduced into cancer therapy.We tested the effect of imatinib on the ovarian histological structure and the concentration ofestrogen and progesterone, luteinizing hormone (LH and follicle stimulating hormone (FSHin the serum of female Wistar rats.Materials and Methods: Two groups of rats (180 ± 15 grams were gavaged with doses of 50and 100 mg/kg body weight imatinib dissolved in distilled water for 14 days. The control groupreceived sterile water. On day 7, after termination of the treatment, blood serum concentrationwas measured with the radioimmunoassay (RIA method. Also, sections (5 μm thick of ovariesstained with hematoxylin and eosin (H&E were investigated histologically.Results: Progesterone concentration in the experimental groups was increased (p<0.001,estrogen and FSH concentrations were decreased (p<0.01, and the LH concentration decreasedbut was not statistically different in comparison with the control group. The weight of ovaries andnumber of atretic follicles in the experimental groups was increased compared with the controlgroup (p<0.05. The diameter of corpus lutea were increased but the number of corpus luteadecreased in both experimental groups (p<0.01.Conclusion: These findings suggest that administration of imatinib may have profound effects onfemale fertility.

  20. Interaction of imatinib mesylate with human serum transferrin: The comparative spectroscopic studies

    Science.gov (United States)

    Śliwińska-Hill, Urszula

    2017-02-01

    Imatinib mesylate (Imt) is a tyrosine kinase inhibitor mainly used in the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (Ph + CML). Human serum transferrin is the most abundant serum protein responsible for the transport of iron ions and many endogenous and exogenous ligands. In this study the mechanism of interactions between the imatinib mesylate and all states of transferrin (apo-Tf, Htf and holo-Tf) has been investigated by fluorescence, ultraviolet-visible (UV-vis), circular dichroism (CD) and zeta potential spectroscopic methods. Based on the experimental results it was proved that under physiological conditions the imatinib mesylate binds to the each form of transferrin with a binding constant c.a. 105 M- 1. The thermodynamic parameters indicate that hydrogen bonds and van der Waals were involved in the interaction of apo-Tf with the drug and hydrophobic and ionic strength participate in the reaction of Htf and holo-Tf with imatinib mesylate. Moreover, it was shown that common metal ions, Zn2 + and Ca2 + strongly influenced apo-Tf-Imt binding constant. The CD studies showed that there are no conformational changes in the secondary structure of the proteins. No significant changes in secondary structure of the proteins upon binding with the drug and instability of apo-Tf-Imt system are the desirable effects from pharmacological point of view.

  1. Roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction.

    Science.gov (United States)

    Liu, Jia-Ming; Shen, Jian-Xiong; Zhang, Jian-Guo; Zhao, Hong; Li, Shu-Gang; Zhao, Yu; Qiu, Giu-Xing

    2012-01-01

    It has been stated that preoperative pulmonary function tests are essential to assess the surgical risk in patients with scoliosis. Arterial blood gas tests have also been used to evaluate pulmonary function before scoliotic surgery. However, few studies have been reported. The aim of this study was to investigate the roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction. This study involved scoliotic patients with moderate or severe pulmonary dysfunction (forced vital capacity arterial blood gas tests and pulmonary function tests before surgery. The arterial blood gas tests included five parameters: partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, alveolar-arterial oxygen tension gradient, pH, and standard bases excess. The pulmonary function tests included three parameters: forced expiratory volume in 1 second ratio, forced vital capacity ratio, and peak expiratory flow ratio. All five parameters of the arterial blood gas tests were compared between the two groups with or without postoperative pulmonary complications by variance analysis. Similarly, all three parameters of the pulmonary function tests were compared. The average coronal Cobb angle before surgery was 97.42° (range, 50° - 180°). A total of 15 (20.5%) patients had postoperative pulmonary complications, including hypoxemia in 5 cases (33.3%), increased requirement for postoperative ventilatory support in 4 (26.7%), pneumonia in 2 (13.3%), atelectasis in 2 (13.3%), pneumothorax in 1 (6.7%), and hydrothorax in 1 (6.7%). No significant differences in demographic characteristics or perioperative factors (P > 0.05) existed between the two groups with or without postoperative pulmonary complications. According to the variance analysis, there were no statistically significant differences in any parameter of the arterial blood gas tests between the two groups. No significant correlation between

  2. Massive Intra-Abdominal Imatinib-Resistant Gastrointestinal Stromal Tumor in a 21-Year-Old Male

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    Ann Falor

    2013-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs in adolescence are far less common than adult GISTs and have varied GIST genotypes that present diagnostic and therapeutic challenges. Here, we discuss a 21-year-old male with diagnosis of unresectable, imatinib-resistant GIST. At initial evaluation, a neoadjuvant treatment approach was recommended. As such, the patient received imatinib over the course of one year. Unfortunately, the GIST increased in size, and a subsequent attempt at surgical resection was aborted fearing infiltration of major vascular structures. The patient was then referred to our institution, at which time imatinib therapy was discontinued. Surgical intervention was again considered and the patient underwent successful resection of massive intra-abdominal GIST with total gastrectomy and Roux-en-Y esophagojejunostomy. Since pediatric GISTs are typically resistant to imatinib, we performed genotype analysis of the operative specimen that revealed KIT mutations associated with imatinib sensitivity and resistance. Given the sequencing data and operative findings, the patient was started postoperatively on sunitinib. This case illustrates the importance of understanding both adult and pediatric GISTs when implementing appropriate treatment regimens. Since the genotype of GISTs dictates phenotypic behavior, mutational analysis is an important component of care especially for adolescents whose disease may mirror the pediatric or adult population.

  3. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

    2010-01-01

    Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

  4. Evaluation of preoperative computed tomography angiography in association with conventional angiography versus computed tomography angiography only, in the endovascular treatment of aortic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Metzger, Patrick Bastos; Novero, Eduardo Rafael; Rossi, Fabio Henrique; Moreira, Samuel Martins; Linhares, Frederico Augusto; Almeida, Bruno Lorencao de; Barbato, Heraldo Antonio; Izukawa, Nilo Mitsuru; Kambara, Antonio Massamitsu, E-mail: patrickvascular@gmail.com [Instituto Dante Pazzanese de Cardiologia, Sao Paulo, SP (Brazil)

    2013-09-15

    Objective: to evaluate the association of conventional angiography (AG) with computed tomography angiography (CTA) as compared with CTA only, preoperatively, in the treatment of aortic diseases. Materials and methods: retrospective study involving patients submitted to endovascular treatment of aortic diseases, in the period from January 2009 to July 2010, with use of preoperative CTA + conventional AG or CTA only. The patients were divided into two groups, namely: G1 - thoracic aortic diseases; and G2 - abdominal aortic diseases. G1 was subdivided into 1A (preoperative AG + CTA) and 1B (preoperative CTA). G2 was subdivided into 2C (CTA + AG) and 2D (CTA only). Results: the authors evaluated 156 patients. In subgroups 1A and 1B, the rate of technical success was, respectively, 100% and 94.7% (p = 1.0); and the rate of therapeutic success was, respectively, 81% and 58% (p = 0.13). A higher number of complications were observed in subgroup 1B (p = 0.057). The accuracy in the calculation of the prosthesis was higher in subgroup 1A (p = 0.065). In their turn, the rate of technical success in subgroups 2C and 2D was, respectively, 92.3% and 98.6% (p = 0.17). The rate of therapeutic success was 73% and 98.6% (p = 0.79). Conclusion: preoperative conventional AG should be reserved for cases where CTA cannot provide all the information in the planning of a therapeutic intervention. (author)

  5. High-grade acute organ toxicity during preoperative radiochemotherapy as positive predictor for complete histopathologic tumor regression in multimodal treatment of locally advanced rectal cancer

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    Wolff, Hendrik Andreas; Herrmann, Markus Karl Alfred; Hennies, Steffen; Rave-Fraenk, Margret; Hess, Clemens Friedrich; Christiansen, Hans [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Gaedcke, Jochen; Liersch, Torsten [Dept. of Surgery, Univ. Medicine Goettingen (Germany); Jung, Klaus [Dept. of Medical Statistics, Univ. Medicine Goettingen (Germany); Hermann, Robert Michael [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Dept. of Radiotherapy and Radiooncology, Aerztehaus am Diako, Bremen (Germany); Rothe, Hilka [Dept. of Pathology, Univ. Medicine Goettingen (Germany); Schirmer, Markus [Dept. of Clinical Pharmacology, Univ. Medicine Goettingen (Germany)

    2010-01-15

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during preoperative radiochemotherapy and complete tumor regression after total mesorectal excision in multimodal treatment of locally advanced rectal cancer. Patients and Methods: From 2001 to 2008, 120 patients were treated. Preoperative treatment consisted of normofractionated radiotherapy at a total dose of 50.4 Gy, and either two cycles of 5-fluorouracil (5-FU) or two cycles of 5-FU and oxaliplatin. Toxicity during treatment was monitored weekly, and any toxicity CTC (Common Toxicity Criteria) {>=} grade 2 of enteritis, proctitis or cystitis was assessed as high-grade organ toxicity for later analysis. Complete histopathologic tumor regression (TRG4) was defined as the absence of any viable tumor cells. Results: A significant coherency between high-grade acute organ toxicity and complete histopathologic tumor regression was found, which was independent of other factors like the preoperative chemotherapy schedule. The probability of patients with acute organ toxicity {>=} grade 2 to achieve TRG4 after neoadjuvant treatment was more than three times higher than for patients without toxicity (odds ratio: 3.29, 95% confidence interval: [1.01, 10.96]). Conclusion: Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors' working group. (orig.)

  6. Response to imatinib in villonodular pigmented synovitis (PVNS) resistant to nilotinib.

    Science.gov (United States)

    Stacchiotti, Silvia; Crippa, Flavio; Messina, Antonella; Pilotti, Silvana; Gronchi, Alessandro; Blay, Jean Y; Casali, Paolo G

    2013-05-13

    Pigmented villonodular synovitis (PVNS) is a rare locally aggressive tumor. PVNS is characterized in most cases by a specific t(1;2) translocation, which fuses the colony stimulating factor-1 (CSF1) gene to the collagen type VIa3 (COL6A3) promoter thus leading through a paracrine effect to the attraction of non-neoplastic inflammatory cells expressing CSF1-receptor. Imatinib is a tirosin-kinase inhibitors (TKI) active against CSF1-receptor whose activity in naïve PVNS was already described. We report on two PVNS patients who responded to imatinib after failure to nilotinib, another CSF1-receptor inhibitor. Since August 2012, 2 patients with progressive, locally advanced PVNS resistant to nilotinib (Patient 1: man, 34 years; Patient 2: woman, 24 years) have been treated with second-line imatinib 400 mg/day. Both patients are evaluable for response. Both patients are still on treatment (7 and 4 months). Patient 1 had a dimensional response by MRI after 2 months from starting imatinib, together with symptomatic improvement. In Patient 2 a metabolic response was detected by [18F]fluorodeoxyglucose-positron emission tomography (PET) at 6 weeks coupled with tumor shrinkage by MRI, and symptomatic improvement. Imatinib showed antitumor activity in 2 patients with nilotinib-resistant PVNS. This observation strengthen the idea that targeted agent with similar profile can give a different clinical result, as already described for gastrointestinal stromal tumor (GIST) patients treated with the same agents. Molecular studies are needed to clarify the biologic mechanism(s) underlying the response.

  7. Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary.

    Science.gov (United States)

    Asadi-Azarbaijani, Babak; Santos, Regiane R; Jahnukainen, Kirsi; Braber, Saskia; van Duursen, Majorie B M; Toppari, Jorma; Saugstad, Ola D; Nurmio, Mirja; Oskam, Irma C

    2017-03-01

    Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (Pprimordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Malnutrition in rectal cancer patients receiving preoperative chemoradiotherapy is common and associated with treatment tolerability and anastomotic leakage.

    Science.gov (United States)

    Yamano, Tomoki; Yoshimura, Mie; Kobayashi, Masayoshi; Beppu, Naohito; Hamanaka, Michiko; Babaya, Akihito; Tsukamoto, Kiyoshi; Noda, Masafumi; Matsubara, Nagahide; Tomita, Naohiro

    2016-04-01

    This study assessed the incidence of malnutrition caused by preoperative chemoradiotherapy (CRT) in rectal cancer patients, which is seemingly underestimated; however, malnutrition affects treatment tolerability, postoperative complications, including anastomotic leakage (AL), and oncological outcomes. Between January 2008 and December 2014, 54 consecutive patients with T3-4, N0-2, M0-1 resectable rectal cancer received CRT comprising 45 Gy radiotherapy and S-1 alone or with irinotecan for 5 weeks and then underwent curative surgery with diverting or permanent stomas 6-8 weeks after CRT. We assessed malnutrition after completion of CRT (5-6 weeks after CRT start date) and at surgery (11-14 weeks after CRT start date), defining weight loss as ≥5 % of pre-CRT weight; this definition differs from commonly used criteria for adverse events. We evaluated the incidence of malnutrition associated with CRT and influence of malnutrition on treatment tolerability, AL, and disease-free survival (DFS). We also assessed the influence of CRT on the rate of postoperative complications by comparing the study group with 61 patients who had undergone excision with diverting or permanent stomas alone. Malnutrition was observed in 51 % of patients after CRT and in 29 % at surgery. Malnutrition after CRT was associated with treatment tolerability, and malnutrition at surgery was significantly associated with AL, which significantly influenced DFS in stage 1-3 patients. Malnutrition caused by CRT is common and is associated with treatment tolerability and AL. Nutritional assessment and support seem indispensable for the rectal cancer patients receiving CRT.

  9. 中国慢性髓性白血病伊马替尼耐药或不耐受患者采用达沙替尼治疗的临床疗效及安全性研究%Research of clinical effect and safety by dasatinib in the treatment of imatinib resistance or intolerance in Chinese chronic myelogenous leukemia patients

    Institute of Scientific and Technical Information of China (English)

    朱琳

    2016-01-01

    ObjectiveTo research application value by dasatinib in the treatment of imatinib resistance or intolerance in chronic myelogenous leukemia(CML).MethodsA total of 90 CML patients with imatinib resistance or intolerance were divided by different medication into control group (nilotinib for treatment) and observation group (dasatinib for treatment), with 45 cases in each group. Observation was made on complete cytogenetic remission (CCyR), complete hematologic remission (CHR), main molecular biology remission (MMR)/complete molecular biology remission (CMR) rates and incidence of adverse reactions in the two groups.Results Comparing with the control group, the observation group had higher CCyR remission rate in chronic period and higher CHR, MMR/CMR rates in acceleration period. The observation group had lower mortality rate and progression rate in in acceleration period and less adverse reaction in treatment. The differences all had statistical significance (P<0.05).ConclusionDasatinib provides remarkable effect and tolerance in treating patients with imatinib resistance or intolerance in chronic myelogenous leukemia. It is worth promoting.%目的:研究达沙替尼在慢性髓性白血病(CML)伊马替尼耐药或不耐受患者中的应用价值。方法根据用药不同将90例CML伊马替尼耐药或不耐受患者随机分为对照组(尼洛替尼治疗)和观察组(达沙替尼治疗),各45例。观察两组完全细胞遗传学(CCyR)、完全血液学(CHR)、主要生物分子学(MMR)/完全分子生物学(CMR)缓解率及不良反应发生率。结果与对照组比较,观察组慢性期患者CCyR缓解率及加速期患者CHR、MMR/CMR缓解率均更高,加速期死亡率及进展率更低,治疗期间不良反应更少,差异均有统计学意义(P<0.05)。结论达沙替尼治疗慢性髓性白血病伊马替尼耐药或不耐受患者的临床疗效优,患者更耐受,值得推广。

  10. Roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction

    Institute of Scientific and Technical Information of China (English)

    LIU Jia-ming; SHEN Jian-xiong; ZHANG Jian-guo; ZHAO Hong; LI Shu-gang; ZHAO Yu; QIU Giu-xing

    2012-01-01

    Background It has been stated that preoperative pulmonary function tests are essential to assess the surgical risk in patients with scoliosis.Arterial blood gas tests have also been used to evaluate pulmonary function before scoliotic surgery.However,few studies have been reported.The aim of this study was to investigate the roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction.Methods This study involved scoliotic patients with moderate or severe pulmonary dysfunction (forced vital capacity <60%) who underwent surgical treatment between January 2002 and April 2010.A total of 73 scoliotic patients (23 males and 50 females) with moderate or severe pulmonary dysfunction were included.The average age of the patients was 16.53 years (ranged 10-44).The demographic distribution,medical records,and radiographs of all patients were collected.All patients received arterial blood gas tests and pulmonary function tests before surgery.The arterial blood gas tests included five parameters:partial pressure of arterial oxygen,partial pressure of arterial carbon dioxide,alveolar-arterial oxygen tension gradient,pH,and standard bases excess.The pulmonary function tests included three parameters:forced expiratory volume in 1 second ratio,forced vital capacity ratio,and peak expiratory flow ratio.All five parameters of the arterial blood gas tests were compared between the two groups with or without postoperative pulmonary complications by variance analysis.Similarly,all three parameters of the pulmonary function tests were compared.Results The average coronal Cobb angle before surgery was 97.42° (range,50°-180°).A total of 15 (20.5%) patients had postoperative pulmonary complications,including hypoxemia in 5 cases (33.3%),increased requirement for postoperative ventilatory support in 4 (26.7%),pneumonia in 2 (13.3%),atelectasis in 2 (13.3%),pneumothorax in 1 (6.7%),and hydrothorax in 1

  11. Imatinib-induced hyperbilirubinemia with UGT1A1 (*28) promoter polymorphism: first case series in patients with gastrointestinal stromal tumor

    Science.gov (United States)

    Saif, Muhammad Wasif; Smith, Melissa Hennessey; Maloney, Antonia; Diasio, Robert B.

    2016-01-01

    Imatinib, an orally administered protein-tyrosine kinase inhibitor (TKI) is indicated for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). Severe hepatotoxicity associated with imatinib is rare, and relationship to polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression and related frequency of hyperbilirubinemia or toxicity are not well known. We present a case series patients who developed hyperbilirubinemia while on oral administration imatinib for treatment of GIST. Genetic testing for polymorphism of UGT1A1 showed the first patient to be homozygous for the UGT1A1 TA7 (*28) polymorphism and the second patient heterozygous for the UGT1A1 TA1 (*28) polymorphism. The first patient had to stop imatinib due to severe and persistent hyperbilirubenemia peaking >3 despite reducing imatininb to only 100 mg every other day while the second patient improved at this dose. Our case series represent the first data associating UGT1A1 polymorphism and imatinib in patients being treated for GIST. Given the prevalence of Gilbert’s syndrome and the increasing use of imatinib, we encourage physicians to be aware of this possible toxicity as hepatotoxicity can be fatal if not managed in a timely fashion. This association is also timely due to recent FDA requirement for testing UGT1A1 polymorphism for nilotinib, another TKI. PMID:27708529

  12. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

    2010-01-01

    Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

  13. Preoperative ultra-rapid opiate detoxification for the treatment of post-operative surgical pain.

    Science.gov (United States)

    Blum, James M; Biel, Sarang S; Hilliard, Paul E; Jutkiewicz, Emily M

    2015-06-01

    Over the past two decades, the prescription of high dose opiate therapy has continued to accelerate in an attempt to treat patients with chronic pain. This presents a substantial challenge when patients on high dose opiate therapy require surgery, as opiate pain relief is a cornerstone of postoperative pain management. These patients have exceptionally challenging pain to control. This is likely due to downregulation of existing opiate receptors and the reluctance of clinicians to increase doses of opiates to exceptionally high levels to facilitate pain relief. We hypothesize that using the method of ultra-rapid opiate detoxification (UROD), it would be possible to rapidly increase the number of opiate receptors and return patients to a more naive state, which would be susceptible to exogenous opiate administration. Validation of this hypothesis is supported by two mechanisms, the first of which are reports of patients that underwent UROD for opiate addition that subsequently suffer respiratory arrests when beginning to rapidly abuse opiates shortly after treatment. Additionally there are data demonstrating the tapering of opiate therapy prior to elective surgery results in better pain control. In conclusion, we hypothesize that patients on chronic high dose opiates could obtain substantially better pain relief if they underwent UROD prior to surgery. This technique could be administered shortly before surgery and may dramatically improve the patients' recoveries.

  14. Effect of pre-operative neoadjuvant chemo-radiotherapy and surgical treatment on resectable esophageal cancer: a Meta-analysis

    Directory of Open Access Journals (Sweden)

    Wei ZHU

    2011-08-01

    Full Text Available Objective To explore the effect of pre-operative adjuvant chemo-radiotherapy and surgical treatment on resectable esophageal cancer.Methods By searching Medline,CENTRAL(the Cochrane Central Register of Controlled trials,EMBASE,CBM(China Biology Medicine and CNKI(China National Knowledge Infrastructure by computer,the data of randomized controlled trials(RCTs of neoadjuvant chemoradiotherapy and surgical treatment for resectable esophageal cancer were selected and analyzed using Stata 11.0 statistical software.The study population was patients with resectable early or medium stage esophageal cancer,the intervention was neoadjuvant chemoradiotherapy(include sequential chemoradiotherapy and concurrent chemoradiotherapy followed with surgical resection,the outcome indices were 1-and 3-year survival rates and local recurrence rate.The combined odds ratio(OR,relative risk(RR and their 95% confidence interval(CI were calculated to estimate the results.Results Nine articles including a total of 1156 patients were finally analyzed in the Meta-analysis.Among all the patients,579 received neoadjuvant chemoradiotherapy(study group and 577 received surgical treatment only(control group.Compared the study group and control group,the OR of 1-and 3-year survival rate was 1.06(95%CI=0.94-1.19,Z=0.97,P=0.33 and 1.30(95%CI=1.07.-1.57,Z=2.67,P=0.008,respectively,and the RR of local recurrence rate was 0.75(95%CI=0.50-1.12,Z=1.40,P=0.162.Conclusions Neoadjuvant chemoradiotherapy could improve the 3-year survival rate of patients with resectable esophageal cancer,but could not decrease the local recurrence rate.

  15. Impact of pre-operative transarterial embolization on the treatment of hepatocellular carcinoma with liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Yu-Fan Cheng; Bruno Jawan; Hock-Liew Eng; Chao-Long Chen; Tung-Liang Huang; Tai-Yi Chen; Yaw-Sen Chen; Chih-Chi Wang; Sheng-Lung Hsu; Leo Leung-Chit Tsang; Po-Lin Sun; King-Wah Chiu

    2005-01-01

    AIM: To determine the effectiveness of pre-liver transplant (LT) transarterial embolization (TAE) in treating hepatocellular carcinoma (HCC) and the patient categories,which are likely to have a good outcome after LT.METHODS: Twenty-nine patients with hepatitis-related cirrhosis and unresectable HCC after LT were studied over a 7-year period. The patients were divided into two groups: group A patients (19/29) received pre-LT TAE,whereas group B (10/29) underwent LT without prior TAE.According to Milan criteria, group A patients were further subdivided into: group A1 (12/19) who met the criteria,and group A2 (7/19) who did not. Patient survivals were compared.RESULTS: In the explanted liver, CT images correlated well with pathological specimens showing that TAE induced massive tumor necrosis (>85%) in 63.1% of patients in group A and all 7 patients in group A2 exhibited tumor downgrading that met Milan criteria. The overall 5-year actuarial survival rate was 80.6%. The TAE group had a better survival (84% at 5 years) than the non-TAE (75% at 4 years). The 3-year survival of group A2 (83%)was also higher than that of group A1 (79%). Tumor necrosis >85% was associated with excellent survival of 100% at 3 years, which was significantly better than the others who showed <85% tumor necrosis (57.1% at 3 years) or who did not have TAE (75% at 3 years).CONCLUSION: TAE is an effective treatment for HCC before LT. Excellent long-term survival was achieved in patients that did not fit Milan criteria. Our results broadened and redefined the selection policy for LT among patients with HCC. Meticulous pre-LT TAE helps in further reducing the rate of dropout from waiting lists and should be considered for patients with advanced HCC.

  16. Imatinib and gastrointestinal stromal tumor (GIST: a selective targeted therapy Imatinib y tumor del estroma gastrointestinal (GIST: un tratamiento selectivo frente a una diana molecular

    Directory of Open Access Journals (Sweden)

    A. Fernández

    2004-10-01

    Full Text Available Gastrointestinal stromal tumors are the most frequent mesenchymal tumors in the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by an anomalous receptor for a growth factor with tyrosine-kinase activity (c-kit. This anomaly causes a permanent activation of the receptor and uncontrolled cell growth. These tumors show a poor response to traditional chemotherapy drugs, and are thus associated with low survival in cases of advanced disease. Imatinib, a tyrosine kinase inhibitor, is an example of selective targeted oncologic therapy that induces improved survival in these patients. We discuss two cases of metastatic gastrointestinal stromal tumors with a good response to imatinib, and also review the pathophysiology and treatment-related outcome of this type of tumors. We include results from clinical phase-III studies.Los tumores del estroma gastrointestinal son los tumores mesenquimales más frecuentes del tracto digestivo y se originan de las células intersticiales de Cajal. Se caracterizan por presentar un receptor para el factor de crecimiento con actividad tirosin kinasa (c-kit anómalo que condiciona su activación permanente y un crecimiento celular incontrolado. Tienen una baja supervivencia en casos de enfermedad avanzada, con escasa respuesta a los agentes quimioterápicos tradicionales. El imatinib es un fármaco inhibidor de la tirosín kinasa y un ejemplo de terapia oncológica selectiva que condiciona un importante aumento en la supervivencia de estos pacientes. Se presentan 2 casos de enfermedad metastásica con buena respuesta a imatinib, así como una revisión sobre la fisiopatología y evolución en el tratamiento de este tipo de tumores, incluyendo resultados de estudios en fase III.

  17. Preoperative factors predictive of postoperative decimal visual acuity ≥ 1.0 following surgical treatment for idiopathic epiretinal membrane

    Directory of Open Access Journals (Sweden)

    Hiroshi Kunikata

    2011-02-01

    Full Text Available Hiroshi Kunikata1, Toshiaki Abe2, Jiro Kinukawa1, Kohji Nishida1,31Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Division of Clinical Cell Therapy, Tohoku University Graduate School of Medicine, Sendai, Japan; 3Department of Ophthalmology, Osaka University Medical School, Suita, JapanPurpose: To report the preoperative best-corrected visual acuity (BCVA and foveal thickness (FT values that lead to a postoperative decimal BCVA of ≥ 1.0 after surgical removal of an idiopathic epiretinal membrane (ERM.Methods: This is a retrospective case series of 73 eyes that underwent surgery for removal of an idiopathic ERM. All eyes had been treated by a single surgeon using a 25-gauge transconjunctival sutureless vitrectomy and indocyanine green-assisted internal limiting membrane peel. The BCVA and FT were measured at baseline and 6 months postoperatively.Results: A postoperative decimal BCVA ≥ 1.0 was obtained in eyes with a preoperative decimal BCVA ≥ 0.3 but not in those with a preoperative decimal BCVA ≤ 0.2. The incidence of obtaining a postoperative decimal BCVA ≥ 1.0 was significantly (P = 0.002 higher in eyes with a preoperative decimal BCVA ≥ 0.5 (50% than in eyes with a preoperative decimal BCVA < 0.5 (11%. Additionally, a postoperative decimal BCVA of ≥ 1.0 was obtained in 51% of the eyes that had a preoperative FT < 400 µm, compared with only 21% of eyes with a preoperative FT ≥ 400 µm (P = 0.01. The incidence of obtaining a postoperative decimal BCVA ≥ 1.0 was significantly higher in eyes with preoperative decimal BCVA ≥ 0.5 and FT < 400 µm (60% than in eyes with preoperative decimal BCVA ≥ 0.5 and FT ≥ 400 µm (20%; P = 0.03 or preoperative BCVA < 0.5 and FT ≥ 400 µm (7%; P < 0.001.Conclusions: These findings indicate that eyes with both preoperative BCVA ≥ 0.5 and FT < 400 µm have a significantly better chance of obtaining a postoperative decimal

  18. The Effect of Apigenin on Pharmacokinetics of Imatinib and Its Metabolite N-Desmethyl Imatinib in Rats

    Directory of Open Access Journals (Sweden)

    Xian-yun Liu

    2013-01-01

    Full Text Available The purpose of this study was to determine the effect of apigenin on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Healthy male SD rats were randomly divided into four groups: A group (the control group, B group (the long-term administration of 165 mg/kg apigenin for 15 days, C group (a single dose of 165 mg/kg apigenin, and D group (a single dose of 252 mg/kg apigenin. The serum concentrations of imatinib and N-desmethyl imatinib were measured by HPLC, and pharmacokinetic parameters were calculated using DAS 3.0 software. The parameters of AUC(0-t, AUC(0−∞, Tmax, Vz/F, and CLz/F for imatinib in group B were different from those in group A (P<0.05. Besides, MRT(0−t and MRT(0−∞ in groups C and D differed distinctly from those in group A as well. The parameters of AUC(0-t and Cmax for N-desmethyl imatinib in group C were significantly lower than those in group A (P<0.05; however, compared with groups B and D, the magnitude of effect was modest. Those results indicated that apigenin in the short-term study inhibited the metabolism of imatinib and its metabolite N-desmethyl imatinib, while in the long-term study the metabolism could be accelerated.

  19. Imatinib induces H2AX phosphorylation and apoptosis in chronic myelogenous leukemia cells in vitro via caspase-3/Mst1 pathway

    Institute of Scientific and Technical Information of China (English)

    Yan-jun ZHANG; Lian-ning DUAN; Cheng-rong LU; Yan CAO; Yuan LUO; Rong-feng BAO; Shu YAN; Mei XUE; Feng ZHU; Zhe WANG

    2012-01-01

    Aim:Histone H2AX is a novel tumor suppressor and its phosphorylation at the C terminus (Ser139 and Tyr142)is required for tumor cell apoptosis.The aim of the present study was to elucidate the mechanisms underlying imatinib-induced C-terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro.Methods:BCR-ABL-positive K562 cells were used.Microscopy,Western blotting and flow cytometry were used to study the signaling pathways that regulate imatinib-induced H2AX phosphorylation and the apoptotic mechanisms.Results:Treatment of K562 cells with imatinib (1-8 μmol/L)induced phosphorylation of H2AX at Ser139 and Tyr142 in time-and dose-dependent manners.In contrast,imatinib at the same concentrations did not affect H2AX acetylation at Lys 5,and the acetylated H2AX maintained a higher level in the cells.Meanwhile,imatinib (1-8 μmol/L)activated caspase-3 and its downstream mammalian STE20-like kinase 1 (Mst1),and induced apoptosis of K562 cells.The caspase-3 inhibitor Z-VAD (40 μmol/L)reduced imatinibinduced H2AX phosphorylation at Ser139 and Tyr142 and blocked imatinib-induced apoptosis of K562 cells.Imatinib (4 μmol/L)induced expression of Williams-Beuren syndrome transcription factor (WSTF),but not wild-type p53-induced phosphatase 1 (Wip1)in K562 cells.Conclusion:The caspase-3/Mst1 pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib.

  20. Slow desensitization of imatinib-induced nonimmediate reactions and dynamic changes of drug-specific CD4(+)CD25(+)CD134(+) lymphocytes.

    Science.gov (United States)

    Klaewsongkram, Jettanong; Thantiworasit, Pattarawat; Sodsai, Pimpayao; Buranapraditkun, Supranee; Mongkolpathumrat, Pungjai

    2016-11-01

    Imatinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumors (GISTs) and certain neoplastic diseases; however, nonimmediate adverse reactions are common. To describe the process of imatinib slow desensitization in patients who experienced nonimmediate reactions to imatinib and the dynamic change in drug-specific CD4(+)CD25(+)CD134(+) T-lymphocyte percentages. Five patients diagnosed as having GISTs and with a recent history of imatinib-induced nonimmediate reactions (maculopapular exanthema with eosinophilia, exfoliative dermatitis, palmar-plantar erythrodysesthesia, and drug rash with eosinophilia and systemic symptoms) were desensitized using a slow desensitization protocol. The reintroduced imatinib dosage was stepped up every week starting from 10 mg/d and increasing to 25, 50, 75, 100, 150, 200, and 300 mg/d until the target dose of 400 mg/d was achieved. Prednisolone of up to 30 mg/d was allowed if allergic reactions recurred. The percentages of CD4(+)CD25(+)CD134(+) T cells present after incubating peripheral blood mononuclear cells with imatinib, at baseline and after successful desensitization, were analyzed using flow cytometric analysis. By using a slow desensitization technique, all patients were able to receive 400 mg/d of imatinib, and prednisolone was gradually tapered off. The percentages of imatinib-induced CD4(+)CD25(+)CD134(+) T cells decreased from a mean (SD) of 11.3% (6.5%) and 13.4% (7.3%) at baseline to 3.2% (0.7%) and 3.0% (1.1%) after successful desensitization, when stimulating peripheral blood mononuclear cells with 1 and 2 μM of imatinib, respectively. Slow desensitization is a helpful procedure in treating patients with imatinib-induced nonimmediate reactions other than simple maculopapular exanthema. The reduced percentages of imatinib-induced CD4(+)CD25(+)CD134(+) T cells in these patients may be associated with immune tolerance. Copyright © 2016 American College of Allergy, Asthma

  1. Systematic analysis of clinical outcomes of anterior maxillary and mandibular subapical osteotomy with preoperative modeling in the treatment of bimaxillary protrusion.

    Science.gov (United States)

    Xie, Fang; Teng, Li; Jin, Xiaolei; Zheng, Jinlong; Xu, Jiajie; Lu, Jianjian; Zhang, Chao; Xu, Meibang; Zeng, Haifeng; Li, Shuyuan; Sun, Xuejian

    2013-11-01

    The purpose of this study was to determine the changes in teeth and hard tissues after preoperative modeling and bimaxillary anterior subapical osteotomy for the treatment of bimaxillary protrusion. Cephalometric analysis was used to evaluate the aesthetic effects and occlusal relationships obtained. The subjects included 19 women and 1 man (aged 19-41 years; average, 29 years) with bimaxillary protrusion who underwent anterior subapical osteotomy of both the maxilla and mandible, with simultaneous genioplasty, if required. Based on a preoperative computer-aided manufacturing/design-assisted and model surgical design and an occlusal guide plate, new occlusal relationships were established for the patients. In addition, the preoperative and postoperative cephalometric radiographs were systematically analyzed. In all patients, the surgical incisions underwent primary healing, with no infection or osteonecrosis. Significant differences were observed in the preoperative and postoperative values of all hard tissue and teeth parameters, except for SGn-FH degrees and Co-MP. The most obvious significant differences were seen in L1-OP°, Id-Pog-Go°, IIA°, U1E-Apog, L1E-Apog, U1E-NA, and L1-NA° (P bimaxillary protrusion with satisfactory postoperative occlusal relationship and facial aesthetic appearance and minimal postoperative complications.

  2. Successful Treatment of Mediastinal Unicentric Castleman’s Disease Using Video-Assisted Thoracoscopic Surgery with Preoperative Embolization

    Directory of Open Access Journals (Sweden)

    Yosuke Amano

    2013-01-01

    Full Text Available Unicentric Castleman’s disease is a rare, benign lymphoproliferative disorder that is curable with surgical resection. However, significant bleeding often occurs during surgery because of tumor hypervascularity. We herein present a case of hyaline-vascular-type mediastinal unicentric Castleman’s disease, successfully resected using video-assisted thoracoscopic surgery with preoperative embolization. In the present case, tumor hypervascularity and feeding vessels were revealed by computed tomography (CT, which led us to perform preoperative angiography and embolization to the tumor feeding arteries to reduce intraoperative bleeding. Castleman’s disease should be considered in the differential diagnosis of hypervascular mediastinal tumors. Tumor vascularity should be assessed prior to surgery, and preoperative embolization should be considered.

  3. Triomics Analysis of Imatinib-Treated Myeloma Cells Connects Kinase Inhibition to RNA Processing and Decreased Lipid Biosynthesis.

    Science.gov (United States)

    Breitkopf, Susanne B; Yuan, Min; Helenius, Katja P; Lyssiotis, Costas A; Asara, John M

    2015-11-03

    The combination of metabolomics, lipidomics, and phosphoproteomics that incorporates triple stable isotope labeling by amino acids in cell culture (SILAC) protein labeling, as well as (13)C in vivo metabolite labeling, was demonstrated on BCR-ABL-positive H929 multiple myeloma cells. From 11 880 phosphorylation sites, we confirm that H929 cells are primarily signaling through the BCR-ABL-ERK pathway, and we show that imatinib treatment not only downregulates phosphosites in this pathway but also upregulates phosphosites on proteins involved in RNA expression. Metabolomics analyses reveal that BCR-ABL-ERK signaling in H929 cells drives the pentose phosphate pathway (PPP) and RNA biosynthesis, where pathway inhibition via imatinib results in marked PPP impairment and an accumulation of RNA nucleotides and negative regulation of mRNA. Lipidomics data also show an overall reduction in lipid biosynthesis and fatty acid incorporation with a significant decrease in lysophospholipids. RNA immunoprecipitation studies confirm that RNA degradation is inhibited with short imatinib treatment and transcription is inhibited upon long imatinib treatment, validating the triomics results. These data show the utility of combining mass spectrometry-based "-omics" technologies and reveals that kinase inhibitors may not only downregulate phosphorylation of their targets but also induce metabolic events via increased phosphorylation of other cellular components.

  4. Proteomics analysis of cellular imatinib targets and their candidate downstream effectors.

    Science.gov (United States)

    Breitkopf, Susanne B; Oppermann, Felix S; Keri, Gyorgy; Grammel, Markus; Daub, Henrik

    2010-11-05

    Inhibition of deregulated protein kinases by small molecule drugs has evolved into a major therapeutic strategy for the treatment of human malignancies. Knowledge about direct cellular targets of kinase-selective drugs and the identification of druggable downstream mediators of oncogenic signaling are relevant for both initial therapy selection and the nomination of alternative targets in case molecular resistance emerges. To address these issues, we performed a proof-of-concept proteomics study designed to monitor drug effects on the pharmacologically tractable subproteome isolated by affinity purification with immobilized, nonselective kinase inhibitors. We applied this strategy to chronic myeloid leukemia cells that express the transforming Bcr-Abl fusion kinase. We used SILAC to measure how cellular treatment with the Bcr-Abl inhibitor imatinib affects protein binding to a generic kinase inhibitor resin and further quantified site-specific phosphorylations on resin-retained proteins. Our integrated approach indicated additional imatinib target candidates, such as flavine adenine dinucleotide synthetase, as well as repressed phosphorylation events on downstream effectors not yet implicated in imatinib-regulated signaling. These included activity-regulating phosphorylations on the kinases Btk, Fer, and focal adhesion kinase, which may qualify them as alternative target candidates in Bcr-Abl-driven oncogenesis. Our approach is rather generic and may have various applications in kinase drug discovery.

  5. Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer : A phase II clinical trial

    NARCIS (Netherlands)

    Eisterer, Wolfgang; de Vries, Alexander; Öfner, Dietmar; Rabl, Hans; Koplmüller, Renate; Greil, Richard; Tschmelitsch, Jöerg; Schmid, Rainer; Kapp, Karin; Lukas, Peter; Sedlmayer, Felix; Höfler, Gerald; Gnant, Michael; Thaler, Josef; Widder, Joachim

    2014-01-01

    BACKGROUND/AIM: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4). PATIENTS AND METHODS: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45

  6. Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer : A phase II clinical trial

    NARCIS (Netherlands)

    Eisterer, Wolfgang; de Vries, Alexander; Öfner, Dietmar; Rabl, Hans; Koplmüller, Renate; Greil, Richard; Tschmelitsch, Jöerg; Schmid, Rainer; Kapp, Karin; Lukas, Peter; Sedlmayer, Felix; Höfler, Gerald; Gnant, Michael; Thaler, Josef; Widder, Joachim

    2014-01-01

    BACKGROUND/AIM: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4). PATIENTS AND METHODS: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 G

  7. Experience of imatinib in the treatment of chronic myelogenous leukemia%甲磺酸伊马替尼治疗慢性粒细胞白血病的临床观察

    Institute of Scientific and Technical Information of China (English)

    梁蓉; 陈协群; 白庆咸; 杨岚; 张涛; 张永清; 朱华锋; 顾宏涛; 高广勋

    2011-01-01

    目的:总结甲磺酸伊马替尼(IM)治疗Ph阳性慢性粒细胞白血病(CML)患者的临床观察体会.方法:收集110例Ph阳性CML慢性期(CP)患者、6例加速期(AP)患者和4例急变期(BC)患者分别口服IM 400、600或800 mg/d.通过血液学、细胞遗传学和分子遗传学指标来判断疗效.结果:CP患者完全血液学反应(CHR)率、主要细胞遗传学反应(MCyR)率和完全细胞遗传学反应(CCyR)率分别为98.2%、90.9%和80.9%;AP分别为66.7%、33.3%和16.7%,P值分别为0.002、0.000和0.000.其中CP患者中肝肾功能不全的患者需减少IM剂量.27例经干扰素治疗失败的CP患者IM治疗仍有效.第1年高随访(1次/月)CP患者CCyR达81.9%,非高随访则为63.6%,P=0.005 2.服药前肾功能不全和肝功能不全较脏器功能正常的CP患者服药6个月内发生3~4级血液学毒副反应概率增高,服药6个月后有所减少.结论:IM对CP患者包括干扰素治疗失败的有较高疗效,对AP和BC患者有一定近期疗效.肝肾功能不全的患者易出现血液学毒副反应,需要药物剂量调整.%OBJECTIVE: To summarize the experience of imatinib mesylate (IM) in the treatment of patients with Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia(CML). METHODS: Totally 110 patients with Ph-positive CML in chronic phase(CP) were treated with IM 400 mg/d; 6 CML patients of accelerated phase(AP) and 4 CML patients with blastcrisis (BC) were treated with IM 600 mg/d and 800 mg/d respectively. RESULTS: Overall complete hematological response(CHR) rate, major cytogenetic response (MCyR) rate and complete cytogenetic response (CCyR) rate of CP were 98. 2%, 90.9% and 80. 9% respectively; while those of AP were 66. 7%, 33. 3% and 16. 7% (P were 0.002,0.000 and 0. 000). Dose reductions were performed in of 97 patients with renal and liver dysfunction. IM was effective in 27 patients with CP who failed in previous IFN-α therapy. CCyR of CP patients with

  8. Regulation of HtrA2 on WT1 gene expression under imatinib stimulation and its effects on the cell biology of K562 cells.

    Science.gov (United States)

    Zhang, Lixia; Li, Yan; Li, Xiaoyan; Zhang, Qing; Qiu, Shaowei; Zhang, Qi; Wang, Min; Xing, Haiyan; Rao, Qing; Tian, Zheng; Tang, Kejing; Wang, Jianxiang; Mi, Yingchang

    2017-09-01

    The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis. Subsequent to treatment with drugs and UCF-101, the proliferative function of K562 cells was detected using MTT assays, and the rate of apoptosis was detected using Annexin V with propidium iodide flow cytometry in K562 cells. The protein levels in the signaling pathway were analyzed using western blotting following treatment with imatinib and UCF-101. In K562 cells, imatinib treatment activated HtrA2 gene at a transcription level, while the WT1 gene was simultaneously downregulated. Following HtrA2 inhibitor (UCF-101) treatment, the downregulation of WT1 increased gradually. At the protein level, imatinib induced the increase in HtrA2 protein level and concomitantly downregulated WT1 protein level. Subsequent to HtrA2 inhibition by UCF-101, the WT1 protein level decreased temporarily, but eventually increased. Imatinib induced apoptosis in K562 cells, but this effect was attenuated by the HtrA2 inhibitor UCF-101, resulting in the upregulation of the WT1 protein level. However; UCF-101 did not markedly change the proliferation inhibition caused by imatinib. Imatinib activated the p38 mitogen activated protein kinase (p38 MAPK) signaling pathway in K562 cells, and UCF-101 affected the activation of imatinib in the p38 MAPK signaling pathway. Imatinib inhibited the extracellular signal-related kinase (ERK1/2) pathway markedly and persistently, but UCF-101

  9. Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It?

    Directory of Open Access Journals (Sweden)

    Olga Meltem Akay

    2016-05-01

    Full Text Available Objective: The aim of this study was to investigate the effects of imatinib mesylate on platelet aggregation and adenosine triphosphate (ATP release in chronic myeloid leukemia patients. Materials and Methods: Platelet aggregation and ATP release induced by 5.0 mM adenosine diphosphate, 0.5 mM arachidonic acid, 1.0 mg/ mL ristocetin, and 2 µg/mL collagen were studied by whole blood platelet lumi-aggregometer in 20 newly diagnosed chronic myeloid leukemia patients before and after imatinib mesylate treatment. Results: At the time of diagnosis, 17/20 patients had abnormal platelet aggregation results; 8 (40% had hypoactivity, 6 (30% had hyperactivity, and 3 (15% had mixed hypo- and hyperactivity. Repeat platelet aggregation studies were performed after a mean of 19 months (min: 5 months-max: 35 months in all patients who received imatinib mesylate during this period. After therapy, 18/20 (90% patients had abnormal laboratory results; 12 (60% had hypoactive platelets, 4 (20% had mixed hypo- and hyperactive platelets, and 2 (10% had hyperactive platelets. Three of the 8 patients with initial hypoactivity remained hypoactive, while 2 developed a mixed picture, 2 became hyperactive, and 1 normalized. Of the 6 patients with initial hyperactivity, 4 became hypoactive and 2 developed a mixed pattern. All of the 3 patients with initial hypo- and hyperactivity became hypoactive. Finally, 2 of the 3 patients with initial normal platelets became hypoactive while 1 remained normal. There was a significant decrease in ristocetin-induced platelet aggregation after therapy (p0.05. Conclusion: These findings indicate that a significant proportion of chronic myeloid leukemia patients have different patterns of platelet function abnormalities and imatinib mesylate has no effect on these abnormalities, with a significant impairment in ristocetin-induced platelet aggregation.

  10. Imatinib resistance: a review of alternative inhibitors in chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Roberta Bitencourt

    2011-12-01

    Full Text Available The development of point mutations in the BCR-ABL kinase domain is the main reason for imatinib resistance in chronic myeloid leukemia. Different detection methods are used in chronic myeloid leukemia monitoring, such as direct sequencing, denaturing high performance liquid chromatography and allele specific polymerase chain reaction. Mutation analysis has become mandatory during patient workup of chronic myeloid leukemia in order for the physician to choose the most suitable tyrosine kinase inhibitor. This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient.

  11. LAM Pilot Study with Imatinib Mesylate (LAMP-1)

    Science.gov (United States)

    2015-10-01

    AD______________ AWARD NUMBER: W81XWH-14-1-0132 TITLE: LAM Pilot Study with Imatinib Mesylate ( LAMP -1) PRINCIPAL INVESTIGATOR: Charlie...AND SUBTITLE LAM Pilot Study with Imatinib Mesylate ( LAMP -1) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0132 5c. PROGRAM ELEMENT...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The LAMP -1 study is

  12. Early detection of response to imatinib therapy for gastrointestinal stromal tumor by using 18F-FDG-positron emission tomography and computed tomography imaging

    Institute of Scientific and Technical Information of China (English)

    Sabri Zincirkeser; Alper Sevinc; M Emin Kalender; Celalettin Camci

    2007-01-01

    A 41-year old female with metastatic gastrointestinal stromal tumor was referred to 18F-FDG-positron emission tomography and computed tomography (PET/CT) scan before and after one-month treatment with imatinib(Glivec(R), Gleevec(R), Novartis, Basel, Switzerland), a tyrosine kinase inhibitor (400 mg/d). Metabolic response was evaluated before and after one month of therapy. The decrease of the maximum standardised uptake value (SUV)was 79% (from 9.8 to 2.1). Positron emission tomography demonstrated complete metabolic response after one-month of imatinib treatment. Additionally, the previous lesion was compared with the coronal computerized tomographic image. There was no difference in the size of the tumor before and after therapy according to CT images. However, metabolic activity was inhibited.18F-FDG-PET is a valuable method for the detection of response to one-month imatinib treatment in patients with gastrointestinal stromal tumors.

  13. Implication of the Autologous Immune System in BCR-ABL Transcript Variations in Chronic Myelogenous Leukemia Patients Treated with Imatinib.

    Science.gov (United States)

    Clapp, Geoffrey D; Lepoutre, Thomas; El Cheikh, Raouf; Bernard, Samuel; Ruby, Jérémy; Labussière-Wallet, Hélène; Nicolini, Franck E; Levy, Doron

    2015-10-01

    Imatinib and other tyrosine kinase inhibitors (TKI) have improved treatment of chronic myelogenous leukemia (CML); however, most patients are not cured. Deeper mechanistic understanding may improve TKI combination therapies to better control the residual leukemic cell population. In analyzing our patients' data, we found that many patients who otherwise responded well to imatinib therapy still showed variations in their BCR-ABL transcripts. To investigate this phenomenon, we applied a mathematical model that integrates CML and an autologous immune response to the patients' data. We define an immune window or a range of leukemic loads for which the autologous immune system induces an improved response. Our modeling results suggest that, at diagnosis, a patient's leukemic load is able to partially or fully suppress the autologous immune response developed in a majority of patients, toward the CML clone(s). Imatinib therapy drives the leukemic population into the "immune window," allowing the patient's autologous immune cells to expand and eventually mount an efficient recognition of the residual leukemic burden. This response drives the leukemic load below this immune window, allowing the leukemic population to partially recover until another weaker immune response is initiated. Thus, the autologous immune response may explain the oscillations in BCR-ABL transcripts regularly observed in patients on imatinib. ©2015 American Association for Cancer Research.

  14. Pregnancy and Accelerated Phase of Myeloid Chronic Leukemia Treated with Imatinib: A Case Report from a Developing Country.

    Science.gov (United States)

    Ngolet, Lydie Ocini; Kocko, Innocent; Elira Dokekias, Alexis

    2016-01-01

    Background. Chronic myeloid leukemia is a hematological malignancy caused by expression of BCR-ABL tyrosine kinase oncogene, product of the t(9;22) Philadelphia translocation. Accelerated phase of this disease marks the onset of advanced rapidly progressive disease unresponsive to many therapies. Pregnancy limits broad number of therapies on patients because of their potential teratogenic effects. We report the case of a pregnant 34-year-old patient on accelerated phase successively managed by imatinib. She achieved a safe pregnancy and delivered at 39 weeks a healthy baby without congenital abnormalities. Our case is unusual because of the accelerated phase of the disease. Case Presentation. A 34-year-old African female with history of chronic phase of myeloid leukemia on imatinib, lost to follow-up for 4 months, presented to the hematological department for abdominal discomfort. Accelerated phase of chronic myeloid leukemia was diagnosed. Complete hematological response was achieved on high doses of imatinib. At the completion of 39 weeks, she delivered a healthy child without congenital anomalies. Conclusion. Despite its teratogenic and embryotoxic effects, front line imatinib is the only effective, well-tolerated treatment for patient on accelerated phase that can be offered to patients in sub-Saharan countries.

  15. Pregnancy and Accelerated Phase of Myeloid Chronic Leukemia Treated with Imatinib: A Case Report from a Developing Country

    Directory of Open Access Journals (Sweden)

    Lydie Ocini Ngolet

    2016-01-01

    Full Text Available Background. Chronic myeloid leukemia is a hematological malignancy caused by expression of BCR-ABL tyrosine kinase oncogene, product of the t(9;22 Philadelphia translocation. Accelerated phase of this disease marks the onset of advanced rapidly progressive disease unresponsive to many therapies. Pregnancy limits broad number of therapies on patients because of their potential teratogenic effects. We report the case of a pregnant 34-year-old patient on accelerated phase successively managed by imatinib. She achieved a safe pregnancy and delivered at 39 weeks a healthy baby without congenital abnormalities. Our case is unusual because of the accelerated phase of the disease. Case Presentation. A 34-year-old African female with history of chronic phase of myeloid leukemia on imatinib, lost to follow-up for 4 months, presented to the hematological department for abdominal discomfort. Accelerated phase of chronic myeloid leukemia was diagnosed. Complete hematological response was achieved on high doses of imatinib. At the completion of 39 weeks, she delivered a healthy child without congenital anomalies. Conclusion. Despite its teratogenic and embryotoxic effects, front line imatinib is the only effective, well-tolerated treatment for patient on accelerated phase that can be offered to patients in sub-Saharan countries.

  16. Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate; the first generation specific tyrosine kinase inhibitor

    Directory of Open Access Journals (Sweden)

    Zimmerman Mark

    2010-12-01

    Full Text Available Abstract Background Chronic Myeloid Leukemia (CML is caused by the abnormal fusion protein BCR-ABL1, a constitutively active tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate is a selective inhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular responses. Patan hospital (Patan, Nepal is one of the Gleevec International Patient Assistance Program (GIPAP centers for patients with CML. Methods A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and Jun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses. Results Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic responses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After a mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission and more than 90% of the patients are still alive. About 30% of patients developed some form of manageable myelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity. Conclusions Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we demonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients with Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic analysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust therapy appropriately.

  17. FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia: A Low-Burden Disease with Dramatic Response to Imatinib - A Report of 5 Cases from South India

    Directory of Open Access Journals (Sweden)

    Anıl Kumar N.

    2014-12-01

    Full Text Available OBJECTIVE: Eosinophilia associated with FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukemia and affected patients are sensitive to imatinib treatment. This study was undertaken to learn the prevalence and associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 26 adult patients presenting with profound eosinophilia (>1.5x109/L. METHODS: Reverse-transcriptase polymerase chain reaction and gel electrophoresis were used for the detection of FIP1L1-PDGFRA rearrangement. RESULTS: Five male patients with splenomegaly carried the FIP1L1-PDGFRA gene rearrangement. All patients achieved complete hematological response within 4 weeks of starting imatinib. One patient had previous deep vein thrombosis and 1 patient had cardiomyopathy, which improved with steroids and imatinib. Conventional cytogenetics was normal in all these patients. No primary resistance to imatinib was noted. CONCLUSION: This study indicates the need to do the FIP1L1-PDGFRA assay in patients with hypereosinophilic syndrome. Prompt treatment of this condition with imatinib can lead to complete hematological response and resolution of the organ damage that can be seen in this setting.

  18. Clinical efficacy of second-generation tyrosine kinase inhibitors in imatinib-resistant gastrointestinal stromal tumors: a meta-analysis of recent clinical trials

    Directory of Open Access Journals (Sweden)

    Wu L

    2014-10-01

    Full Text Available Lile Wu, Zhongqiang Zhang, Hongliang Yao, Kuijie Liu, Yu Wen, Li Xiong Department of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China Background: Primary and secondary resistance to imatinib, a selective receptor tyrosine kinase inhibitor (TKI, is a serious clinical problem in the control of advanced gastrointestinal stromal tumors (GIST. Here we report on a meta-analysis we performed to evaluate the efficacy of second-generation TKIs in the treatment of patients with imatinib-resistant GIST.Methods: Randomized controlled trials evaluating the clinical efficacy of second-generation TKIs were identified by searching PubMed and EMBASE from 2000 to February 2014. Outcomes subjected to analysis were progression-free survival and overall survival. Statistical analyses were performed using Review Manager version 5.1.0 (Cochrane Collaboration, Oxford, UK. Weighted hazard ratios (HR with 95% confidence intervals (CIs were calculated for the outcomes. Fixed-effects or random-effects models were used, depending on the degree of heterogeneity across the selected studies.Results: Three randomized controlled trials were selected for meta-analysis. Among imatinib-resistant or imatinib-intolerant patients, 541 received second-generation TKIs (sunitinib, nilotinib, or regorafenib and 267 controls received placebo or best supportive care. Progression-free survival was significantly improved in the TKI-treated group (HR 0.38; 95% CI 0.24–0.59; P<0.0001. No statistically significant difference was detected in overall survival between the treatment group and the control group (HR 0.85; 95% CI 0.71–1.03; P=0.09. In the subgroup of patients who were resistant or intolerant to both imatinib and sunitinib, TKI therapy (nilotinib or regorafenib improved progression-free survival (HR 0.40; 95% CI 0.19–0.84; P=0.02 but not overall survival (HR 0.83; 95% CI 0.63–1.08; P=0.17. Regorafenib was shown to be

  19. Increased financial burden among patients with chronic myelogenous leukaemia receiving imatinib in Japan: a retrospective survey

    Directory of Open Access Journals (Sweden)

    Kodama Yuko

    2012-04-01

    Full Text Available Abstract Background The financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML who have been treated with imatinib. Methods A questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008. Results A total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15–94. A financial burden was felt by 41.2 % (28 of 68 of the patients treated with imatinib in 2000, 70.8 % (201 of 284 in 2005, and 75.8 % (400 of 528 in 2008. Overall, 182 patients (31.7 % considered its discontinuation because of the financial burden and 15 (2.6 % temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients’ median annual household incomes were 49,615 US Dollars (USD, 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95–0.98, p ≪ 0.0001 for 1-year increments, and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85–0.99, p = 0.03 for 10,000 USD-increments were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co-payments (OR = 2.21, 95 % CI: 1.28–4.28, p = 0.004 for 10,000 USD-increments were more likely to have considered discontinuing their imatinib treatment. Conclusions The proportion of CML patients who sensed a financial burden increased between 2000 and 2008

  20. BCR-ABL isoforms associated with intrinsic or acquired resistance to imatinib : more heterogeneous than just ABL kinase domain point mutations?

    NARCIS (Netherlands)

    Gruber, Franz X.; Lundan, Tuija; Goll, Rasmus; Silye, Aleksandra; Mikkola, Ingvild; Rekvig, Ole Petter; Knuutila, Sakari; Remes, Kari; Gedde-Dahl, Tobias; Porkka, Kimmo; Hjorth-Hansen, Henrik

    2012-01-01

    Imatinib, a small molecule inhibitor of ABL, PDGFR and C-KIT, has revolutionized treatment of chronic myeloid leukaemia (CML). However, resistance to treatment is of increasing importance and often is due to point mutations in the Abl kinase domain (Abl KD). Here, we analysed clinical outcome and mu

  1. [Prolonged molecular response induced by imatinib in Philadelphia positive acute lymphoblastic leukemia A case report and brief review].

    Science.gov (United States)

    Raissi, Abderrahim; Bouaouad, Majdouline; Drideb, Noufissa Alami; Jennane, Selim; Mahtat, El Mahdi; Doghmi, Kamal; Mikdame, Mohammed

    2015-01-01

    Philadelphia or BCR-ABL positive acute lymphoblastic leukemia (PH+ ALL) is the most common and severe of adult ALL. The only potentially curator treatment remains allogeneic hematopoietic stem cells transplantation (SCT) in first complete remission. The use of imatinib has revolutionized the treatment of chronic myeloid leukemia. Its incorporation into PH + ALL protocols also improved the prognosis of this disease giving better complete remission rates compared to chemotherapy alone. The treatment of patients not eligible for SCT remains controversial. Prolonged use of high dose tyrosine kinase inhibitors (TKI) (ie: imatinib at 600 or 800 mg/j) as maintenance therapy seems to be a reasonable approach. We present a case of prolonged molecular remission of PH+ ALL under TKI alone as maintenance therapy.

  2. Combination short-course preoperative irradiation, surgical resection, and reduced-field high-dose postoperative irradiation in the treatment of tumors involving the bone.

    Science.gov (United States)

    Wagner, Timothy D; Kobayashi, Wendy; Dean, Susan; Goldberg, Saveli I; Kirsch, David G; Suit, Herman D; Hornicek, Francis J; Pedlow, Francis X; Raskin, Kevin A; Springfield, Dempsey S; Yoon, Sam S; Gebhardt, Marc C; Mankin, Henry J; Delaney, Thomas F

    2009-01-01

    To assess the feasibility and outcomes of combination short-course preoperative radiation, resection, and reduced-field (tumor bed without operative field coverage) high-dose postoperative radiation for patients with solid tumors mainly involving the spine and pelvis. Between 1982 and 2006, a total of 48 patients were treated using this treatment strategy for solid tumors involving bone. Radiation treatments used both photons and protons. Of those treated, 52% had chordoma, 31% had chondrosarcoma, 8% had osteosarcoma, and 4% had Ewing's sarcoma, with 71% involving the pelvis/sacrum and 21% elsewhere in the spine. Median preoperative dose was 20 Gy, with a median of 50.4 Gy postoperatively. With 31.8-month median follow-up, the 5-year overall survival (OS) rate is 65%; 5-year disease-free survival (DFS) rate, 53.8%; and 5-year local control (LC) rate, 72%. There were no significant differences in OS, DFS, and LC according to histologic characteristics. Between primary and recurrent disease, there was no significant difference in OS rates (74.4% vs. 51.4%, respectively; p = 0.128), in contrast to DFS (71.5% vs. 18.3%; p = 0.0014) and LC rates (88.9% vs. 30.9%; p = 0.0011) favoring primary disease. After resection, 10 patients experienced delayed wound healing that did not significantly impact on OS, DFS, or LC. This approach is promising for patients with bone sarcomas in which resection will likely yield close/positive margins. It appears to inhibit tumor seeding with an acceptable rate of wound-healing complications. Dose escalation is accomplished without high-dose preoperative radiation (likely associated with higher rates of acute wound healing delays) or large-field postoperative radiation only (likely associated with late normal tissue toxicity). The LC and DFS rates are substantially better for patients with primary than recurrent sarcomas.

  3. Histologic changes associated with false-negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node-positive breast cancer before treatment.

    Science.gov (United States)

    Brown, Alexandra S; Hunt, Kelly K; Shen, Jeannie; Huo, Lei; Babiera, Gildy V; Ross, Merrick I; Meric-Bernstam, Funda; Feig, Barry W; Kuerer, Henry M; Boughey, Judy C; Ching, Christine D; Gilcrease, Michael Z

    2010-06-15

    A wide range of false-negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node-positive disease before treatment. Eighty-six patients with confirmed lymph node-positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin-stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated. Forty-seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false-negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true-negative SLNs and in only 2 (18%) of 11 patients with false-negative SLNs (P = .03, Fisher exact test, 2-tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false-negative SLN of 82% and 65%, respectively. Absence of treatment effect in SLNs after chemotherapy in patients with lymph node-positive disease at initial presentation has good sensitivity but low specificity for identifying a false-negative SLN.

  4. 75 FR 76017 - Determination That GLEEVEC (Imatinib Mesylate) Capsules, 50 Milligrams and 100 Milligrams, Were...

    Science.gov (United States)

    2010-12-07

    ... HUMAN SERVICES Food and Drug Administration Determination That GLEEVEC (Imatinib Mesylate) Capsules, 50... determined that GLEEVEC (imatinib mesylate) Capsules, 50 milligrams (mg) and 100 mg, were not withdrawn from... new drug applications (ANDAs) for imatinib mesylate capsules, 50 mg and 100 mg, if all other legal and...

  5. Morphological Changes in Bone Marrow Post Imatinib Therapy in Chronic Phase CML: A Follow up Study on Sequential Bone Marrow Aspirates and Biopsies.

    Science.gov (United States)

    Narang, Neha Chopra; Rusia, Usha; Sikka, Meera; Kotru, Mrinalini

    2017-04-01

    Imatinib mesylate is used extensively for first line treatment of Chronic Myeloid Leukemia (CML). However, not many studies have documented morphological changes in bone marrow biopsies produced during Imatinib therapy with reference to myelofibrosis. To document the morphological changes produced in the bone marrow during Imatinib therapy. This longitudinal study followed up 75 Philadelphia Chromosome Positive Chronic Myeloid Leukemia with chronic phase(Ph+ CML- CP) patients sequentially, receiving 400-600mg Imatinib over a period of 12 or more months. Haematologic parameters were measured at admission, 2 weeks, 1 month, 3 months, 6 months and 12 or more months. Morphologic changes in bone marrow aspirate and biopsy were evaluated at admission, 6 months and ≥12 months of treatment in accordance with National Comprehensive Cancer Network(NCCN) guidelines. Complete Haematologic Response (CHR) was seen in 47.1%, 80%, 85.4%, 90.4% at ≥1 month, 3 months, 6 months and 12 months respectively after therapy. It was noted that patients not showing CHR by 3 months were less likely to show CHR at 6 months and beyond. Bone marrow aspirates and biopsies showed reduction in cellularity and myeloid precursors with regeneration of erythroid precursors in 70-83% at ≥12 months. A significant decrease in myelofibrosis (p-value< 0.04) was noted as early as 6 months. Mild to moderate hypoplasia was noted in 31.8% of biopsies within 6 months. Pseudo gaucher cells and benign lymphoid nodules were also seen. Sequential analysis showed that Imatinib reduced the grade of myelofibrosis significantly (p-value< 0.04). It also prevented development of myelofibrosis in patients who did not have it at presentation. Hence Imatinib is effective when used early in the course of CML-CP.

  6. Imatinib Spares cKit-Expressing Prostate Neuroendocrine Tumors, whereas Kills Seminal Vesicle Epithelial-Stromal Tumors by Targeting PDGFR-β.

    Science.gov (United States)

    Jachetti, Elena; Rigoni, Alice; Bongiovanni, Lucia; Arioli, Ivano; Botti, Laura; Parenza, Mariella; Cancila, Valeria; Chiodoni, Claudia; Festinese, Fabrizio; Bellone, Matteo; Tardanico, Regina; Tripodo, Claudio; Colombo, Mario P

    2017-02-01

    Prostate cancer is a leading cause of cancer-related death in males worldwide. Indeed, advanced and metastatic disease characterized by androgen resistance and often associated with neuroendocrine (NE) differentiation remains incurable. Using the spontaneous prostate cancer TRAMP model, we have shown that mast cells (MCs) support in vivo the growth of prostate adenocarcinoma, whereas their genetic or pharmacologic targeting favors prostate NE cancer arousal. Aiming at simultaneously targeting prostate NE tumor cells and MCs, both expressing the cKit tyrosine kinase receptor, we have tested the therapeutic effect of imatinib in TRAMP mice. Imatinib-treated TRAMP mice experience a partial benefit against prostate adenocarcinoma, because of inhibition of supportive MCs. However, they show an unexpected outgrowth of prostate NE tumors, likely because of defective signaling pathway downstream of cKit receptor. Also unexpected but very effective was the inhibition of epithelial-stromal tumors of the seminal vesicles achieved by imatinib treatment. These tumors normally arise in the seminal vesicles of TRAMP mice, independently of the degree of prostatic glandular lesions, and resemble phyllodes tumors found in human prostate and seminal vesicles, and in breast. In both mice and in patients, these tumors are negative for cKit but express PDGFR-β, another tyrosine kinase receptor specifically inhibited by imatinib. Our results imply a possible detrimental effect of imatinib in prostate cancer patients but suggest a promising therapeutic application of imatinib in the treatment of recurrent or metastatic phyllodes tumors. Mol Cancer Ther; 16(2); 365-75. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. Preoperative staging of rectal cancer.

    Science.gov (United States)

    Smith, Neil; Brown, Gina

    2008-01-01

    Detailed preoperative staging using high resolution magnetic resonance imaging (MRI) enables the selection of patients that require preoperative therapy for tumour regression. This information can be used to instigate neoadjuvant therapy in those patients with poor prognostic features prior to disturbing the tumour bed and potentially disseminating disease. The design of trials incorporating MR assessment of prognostic factors prior to therapy has been found to be of value in assessing treatment modalities and outcomes that are targeted to these preoperative prognostic subgroups and in providing a quantifiable assessment of the efficacy of particular chemoradiation treatment protocols by comparing pre-treatment MR staging with post therapy histology assessment. At present, we are focused on achieving clear surgical margins of excision (CRM) to avoid local recurrence. We recommend that all patients with rectal cancer should undergo pre-operative MRI staging. Of these, about half will have good prognosis features (T1-T3b, N0, EMVI negative, CRM clear) and may safely undergo primary total mesorectal excision. Of the remainder, those with threatened or involved margins will certainly benefit from pre-operative chemoradiotherapy with the aim of downstaging to permit safe surgical excision. In the future, our ability to recognise features predicting distant failure, such as extramural vascular invasion (EMVI) may be used to stratify patients for neo-adjuvant systemic chemotherapy in an effort to prevent distant relapse. The optimal pre-operative treatment regimes for these patients (radiotherapy alone, systemic chemotherapy alone or combination chemo-radiotherapy) is the subject of current and future trials.

  8. Imatinib Reverses Doxorubicin Resistance by Affecting Activation of STAT3-Dependent NF-κB and HSP27/p38/AKT Pathways and by Inhibiting ABCB1

    Science.gov (United States)

    Sims, Jonathan T.; Ganguly, Sourik S.; Bennett, Holly; Friend, J. Woodrow; Tepe, Jessica; Plattner, Rina

    2013-01-01

    Despite advances in cancer detection and prevention, a diagnosis of metastatic disease remains a death sentence due to the fact that many cancers are either resistant to chemotherapy (conventional or targeted) or develop resistance during treatment, and residual chemoresistant cells are highly metastatic. Metastatic cancer cells resist the effects of chemotherapeutic agents by upregulating drug transporters, which efflux the drugs, and by activating proliferation and survival signaling pathways. Previously, we found that c-Abl and Arg non-receptor tyrosine kinases are activated in breast cancer, melanoma, and glioblastoma cells, and promote cancer progression. In this report, we demonstrate that the c-Abl/Arg inhibitor, imatinib (imatinib mesylate, STI571, Gleevec), reverses intrinsic and acquired resistance to the anthracycline, doxorubicin, by inducing G2/M arrest and promoting apoptosis in cancer cells expressing highly active c-Abl and Arg. Significantly, imatinib prevents intrinsic resistance by promoting doxorubicin-mediated NF-κB/p65 nuclear localization and repression of NF-κB targets in a STAT3-dependent manner, and by preventing activation of a novel STAT3/HSP27/p38/Akt survival pathway. In contrast, imatinib prevents acquired resistance by inhibiting upregulation of the ABC drug transporter, ABCB1, directly inhibiting ABCB1 function, and abrogating survival signaling. Thus, imatinib inhibits multiple novel chemoresistance pathways, which indicates that it may be effective in reversing intrinsic and acquired resistance in cancers containing highly active c-Abl and Arg, a critical step in effectively treating metastatic disease. Furthermore, since imatinib converts a master survival regulator, NF-κB, from a pro-survival into a pro-apoptotic factor, our data suggest that NF-κB inhibitors may be ineffective in sensitizing tumors containing activated c-Abl/Arg to anthracyclines, and instead might antagonize anthracycline-induced apoptosis. PMID:23383209

  9. Preoperative subconjunctival injection of mitomycin C versus intraoperative topical application as an adjunctive treatment for surgical removal of primary pterygium

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    Ehab M Ghoneim

    2011-01-01

    Materials and Methods : Seventy eyes of 70 patients with primary pterygia were randomly allocated to two groups. The first group (Group A, 35 eyes received 0.1 ml of 0.15 mg/ml of subconjunctival MMC injected into the head of the pterygium 24 h before surgical excision with the bare sclera technique. The second group (Group B 35 eyes underwent surgical removal with the bare sclera technique with intraoperative application of MMC (0.15 mg/ml over bare sclera for 3 min. The study was performed between March 2007 and December 2008, and follow up was performed for 1 year postoperatively. Differences between frequencies in both groups were compared by the Chi-square test or Fisher exact test. Differences between means in both groups were compared by Student′s t-test. P 0.05. Postoperatively, scleral thinning occurred in one eye in each group that resolved by 5 months postoperatively. No serious postoperative complications occurred in either group. Conclusion : Preoperative local injection of 0.15 mg/ml MMC is as effective as intraoperative topical application of 0.15 mg/ml MMC for preventing pterygium recurrence after surgical removal.

  10. Preoperative medical treatment in patients undergoing diabetic foot surgery with a Wagner Grade-3 or higher ulcer: a retrospective analysis of 52 patients

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    Murat Korkmaz

    2012-08-01

    Full Text Available Diabetic foot ulcers (DFU are one of the most important complications in people with diabetes mellitus. The present study was aimed to retrospectively review the efficacy of at least 1-week medical treatment before any surgical intervention in patients with Grade-3 and higher DFU according to Wagner's classification. A total of 52 patients (36 males and 16 females hospitalized and treated between June 2006 and February 2009 and had initially received therapeutic treatment (local wound care, antibiotic therapy and blood glucose regulation for a period of at least 1 week were included in the study. The level of amputation, rates of reulceration and mortality in both groups were recorded in the following period of 2 years. Group 1 (did not respond to preoperative medical intervention included 16 patients where a surgical debridement, flap or skin graft surgery was performed in 2 (12.5% patients, major amputation was performed in another 2 (12.5% patients and minor amputation was performed in the remaining 12 (75% patients. Of 36 patients in Group 2 (did respond to preoperative medical intervention, 5 (13.9% patients underwent the surgical debridement, flap or skin graft surgery, 8 (22.2% patients had a major amputation and the remaining 23 (63.9% patients lead to a minor amputation. The ulcer recurrence and mortality rates were obtained as 2 (12.5% and 2 (12.5% in Group 1 and 2 (5.6% and 1 (2.8% in Group 2, respectively. Despite the lower rates of ulcer recurrence and mortality in patients having adequate responses to initial treatment before surgical procedures were performed, no statistically significant difference was observed between the 2 groups. In addition, there was no statistically significant difference between the levels of amputation in both groups.

  11. Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts.

    Science.gov (United States)

    Kirschner, Gyöngyi; Balla, Bernadett; Horváth, Péter; Kövesdi, Andrea; Lakatos, Gergely; Takács, István; Nagy, Zsolt; Tóbiás, Bálint; Árvai, Kristóf; Kósa, János Pál; Lakatos, Péter

    2016-09-01

    Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.

  12. Insufficient bilateral femoral subtrochanteric fractures in a patient receiving imatinib mesylate.

    Science.gov (United States)

    Yang, Kyu-Hyun; Park, Si-Young; Park, Sang-Won; Lee, Soon-Hyuck; Han, Seung-Beom; Jung, Woong-Kyo; Kim, Suk-Jin

    2010-11-01

    We present a case of insufficient bilateral femoral subtrochanteric fractures in a patient who was treated with imatinib mesylate, an anticancer drug, for 1 year after a diagnosis of chronic myelogenous leukemia (CML). A 60-year-old woman presented with bilateral thigh pain for 6 months. A plain radiograph revealed bilateral progressive insufficient fractures on the subtrochanteric areas of the femurs. MRI of the femurs revealed incomplete stress fractures and no evidence of bone metastasis on either femur. Bone densitometry showed normal T-scores around the hip joint and spine. The patient had normal serum levels of calcium, vitamin D derivatives, and thyroid hormones. Serum phosphate levels were decreased, and parathyroid hormone levels were increased. Serum osteocalcin and urinary N-telopeptide of collagen cross-links (NTx) were both decreased. A bone biopsy demonstrated normocellular marrow without leukemic cells. A histomorphometric evaluation of her bones revealed reduced bone turnover despite secondary hyperparathyroidism. The serum markers for bone metabolism and histomorphometric evaluations in this patient suggest that the drug may have an effect on bone metabolism. These effects could be seen for both bone formation and resorption: this could result in impaired bone mineralization, a severely suppressed bone turnover rate, insufficient fractures, and bone necrosis, which are sometimes seen with long-term use of bisphosphonates. To our knowledge, this is the first case of an insufficient bilateral femoral shaft fracture that is potentially related to the use of imatinib mesylate in a patient with CML. Careful examination of bone metabolism should be performed in patients with CML because imatinib mesylate treatment is a lifelong process.

  13. A V530I Mutation in c-KIT Exon 10 Is Associated to Imatinib Response in Extraabdominal Aggressive Fibromatosis

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    Jean-Emmanuel Kurtz

    2010-01-01

    Full Text Available Aggressive fibromatosis (AF or desmoid tumor is a rare condition, characterized by deep tissue invasion by a monoclonal fibroblastic neoplasm, developed from musculoaponeurotic structures. Surgery is the treatment of choice, but negative margins can hardly been achieved in large tumors, and can lead to major functional disability. AF medical therapy includes nonsteroids anti-inflammatory drugs, tamoxifen, with inconsistent results. Several reports of imatinib efficacy in AF appear in the literature. Here, we describe for the first time a V530I KIT exon 10 mutant that was associated to a dramatic imatinib response in an extraabdominal aggressive fibromatosis. The previously discovered V530I substitution was characterized in the core binding factor AML, but had never been reported in any other condition, so far. In this paper, we discuss the KIT exon 10 mutations or polymorphisms that have been described in a variety of KIT-related conditions, including acute myelogenous leukemia, mastocytosis, and aggressive fibromatosis.

  14. Preoperative staging of perforated diverticulitis by computed tomography scanning

    NARCIS (Netherlands)

    M.P.M. Gielens; I.M. Mulder (Irene); E. van der Harst (Erwin); M.P. Gosselink (Martijn Pieter); K.J. Kraal; H.T. Teng; J.F. Lange (Johan); J. Vermeulen (Jefrey)

    2012-01-01

    textabstractBackground: Treatment of perforated diverticulitis depends on disease severity classified according to Hinchey's preoperative classification. This study assessed the accuracy of preoperative staging of perforated diverticulitis by computerized tomography (CT) scanning. Methods: All patie

  15. Preoperative glucocorticoid use and risk of postoperative bleeding and infection after gastric bypass surgery for the treatment of obesity.

    Science.gov (United States)

    Gribsholt, Sigrid Bjerge; Svensson, Elisabeth; Thomsen, Reimar Wernich; Richelsen, Bjørn; Sørensen, Henrik Toft

    2015-01-01

    Previous research suggests that patients using glucocorticoids may be at increased risk of postoperative bleeding and infection after major surgery. The objective was to investigate the association between preoperative glucocorticoid use and risk of bleeding and infection after Roux-en-Y gastric bypass surgery (RYGB). Nationwide cohort study of 13,195 patients, who underwent RYGB 2006-2012 using Danish population-based medical databases. Information was obtained on current (redeemed prescriptionsurgery), recent (prescription 60-180 d before surgery), or no glucocorticoid use, and postoperative bleeding or infection within 30 days of surgery. We computed risk differences and odds ratios (ORs) as a measure of relative risk with 95% confidence intervals (95% CIs) for the association between glucocorticoid use and bleeding or infection, adjusting for gender, age, and co-morbidities by logistic regression. Among RYGB patients, 325 (2.5%) were current glucocorticoid users, and 365 (2.8%) were recent users. The risk of bleeding was increased in current users: 2.8% versus 1.6% among nonusers (risk difference: 1.2%, 95% CI: -.6, 3.0) corresponding to an adjusted OR of 1.5 (95% CI: .8, 3.0). For recent users, the adjusted OR for bleeding was 1.2 (95% CI: .5, 2.5). The risk of infection did not differ materially between current (1.8%), recent (1.0%) and nonusers (1.7%), corresponding to an adjusted OR of .9 (95% CI: .4, 2.1) among current versus nonusers. Current use of glucocorticoids is associated with a slightly increased risk of postoperative bleeding, but not infection, after RYGB. No increased risks were found for recent users. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  16. Successful Peripheral Blood Stem Cells Collection in Imatinib Pretreated and Nilotinib-Treated Chronic Myeloid Leukemia Patient

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    Samuel Vokurka

    2010-01-01

    Full Text Available We report a case of a successful mobilization and harvest of the peripheral blood stem cells (PBSCs in imatinib-pretreated and nilotinib treated 52-year-old woman diagnosed with Philadelphia chromosome-positive and BCR-ABL (b2a2 positive chronic phase CML in 2/2002. She failed interferon-alfa and imatinib treatment. She achieved her first complete molecular remission after 16 months of nilotinib treatment and later on was mobilized with filgrastim at a dose of 10 ug/kg/day applied subcutaneously once daily. The total number of 2.98×106 CD34+ cells/kg was harvested on the fourth day of the mobilization. The autologous graft of the stem cells was cryopreserved and tested for the residual disease: the FISH revealed negative results and the RT-PCR was positive (BCR-ABL/ABL ratio 0,0017 in RQ-PCR. To our knowledge, this is the first report of successful PBSC harvest in a patient significantly pretreated with imatinib and nilotinib.

  17. Efficacy and Safety of High-dose Imatinib in the Treatment of Chronic Myeloid Leukemia in Chronic Phrase:A Meta -analysis%高剂量伊马替尼治疗慢性髓细胞白血病慢性期疗效与安全性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    李浩; 付美兰

    2015-01-01

    Objective To compare the efficacy and safety between high -dose imatinib( IM,≥600 mg/d)and standard-dose imatinib(400 mg/d)in the treatment of chronic myeloid leukemia in chronic phrase(CML-CP). Methods We made computer-based retrieval in PubMed,EMBase,CNKI,CBM,Wanfang database and VIP for randomized controlled trials( RCTs)which trial group was administrated with high-dose imatinib and control group was administrated with standard-dose imatinib. The Cochrane Collaboration′s tool for assessing risk of bias was employed to evaluate the quality of included literatures,and the RevMan 5. 2 software of Cochrane Collaboration was used to make statistic analysis. The subjects taking high-dose IM and those taking standard IM were compared in CCyR,MMR,OS,PFS and adverse reaction. Results Two groups were not significantly different in the CCyR incidence 3 months after intervention〔RR=2. 08,95%CI(0. 73,5. 90),P=0. 17〕. Trial group was higher than control group in CCyR 6 months and 12 months after intervention〔RR =1. 34,95%CI (1. 20,1. 49),P<0. 001;RR=1. 16,95%CI(1. 07,1. 25),P<0. 001〕. Trial group was higher than control group in MMR 3 months,6 months and 12 months after intervention〔RR =2. 97,95%CI(1. 75,5. 05),P <0. 01;RR =2. 02, 95%CI(1. 38,2. 93),P <0. 001;RR =1. 28,95%CI(1. 14,1. 44),P <0. 001〕. Two groups were not significantly different in OS〔RR=1. 00,95%CI(0. 98,1. 02),P=0. 86〕. Trial group was higher than control group in PFS〔RR=1. 04,95%CI(1. 00,1. 09),P =0. 04〕. Trial group was higher than control group in the incidence of neutropenia and thrombocytopenia〔RR =1. 55,95%CI(1. 13,2. 11),P =0. 006;RR =1. 92,95%CI(1. 28,2. 86),P =0. 001〕. Trial group was higher than control group in the incidence of myalgia,adverse reaction in digestive system〔RR=2. 89,95%CI (1. 17,7. 14),P<0. 05;RR =3. 46,95%CI(1. 34,8. 97),P <0. 05〕. Conclusion High - dose imatinib in the treatment of CML - CP patients may increase PFS and the incidence of CCyR and MMR

  18. Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment

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    Kuo Chao-Hung

    2009-08-01

    Full Text Available Abstract Background The aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC undergoing surgical treatment. Methods Between January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely. Results Of 1367 CRC patients, there were seven hundred and fifty-seven males (55.4% and 610 (44.6% females. The median follow-up period was 60 months (range, 3–132 months. A multivariate analysis identified that low serum albumin level (P = 0.011, advanced UICC stage (P P P P P Conclusion Preoperative serum albumin level, CEA level and age could prominently affect postoperative outcome of CRC patients undergoing surgical treatment. In addition to conventional UICC staging system, it might be imperative to take these additional characteristics of factors into account in CRC patients prior to surgical treatment.

  19. Distinct Dasatinib-Induced Mechanisms of Apoptotic Response and Exosome Release in Imatinib-Resistant Human Chronic Myeloid Leukemia Cells

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    Juan Liu

    2016-04-01

    Full Text Available Although dasatinib is effective in most imatinib mesylate (IMT-resistant chronic myeloid leukemia (CML patients, the underlying mechanism of its effectiveness in eliminating imatinib-resistant cells is only partially understood. This study investigated the effects of dasatinib on signaling mechanisms driving-resistance in imatinib-resistant CML cell line K562 (K562RIMT. Compared with K562 control cells, exsomal release, the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt/ mammalian target of rapamycin (mTOR signaling and autophagic activity were increased significantly in K562RIMT cells and mTOR-independent beclin-1/Vps34 signaling was shown to be involved in exosomal release in these cells. We found that Notch1 activation-mediated reduction of phosphatase and tensin homolog (PTEN was responsible for the increased Akt/mTOR activities in K562RIMT cells and treatment with Notch1 γ-secretase inhibitor prevented activation of Akt/mTOR. In addition, suppression of mTOR activity by rapamycin decreased the level of activity of p70S6K, induced upregulation of p53 and caspase 3, and led to increase of apoptosis in K562RIMT cells. Inhibition of autophagy by spautin-1 or beclin-1 knockdown decreased exosomal release, but did not affect apoptosis in K562RIMT cells. In summary, in K562RIMT cells dasatinib promoted apoptosis through downregulation of Akt/mTOR activities, while preventing exosomal release and inhibiting autophagy by downregulating expression of beclin-1 and Vps34. Our findings reveal distinct dasatinib-induced mechanisms of apoptotic response and exosomal release in imatinib-resistant CML cells.

  20. An update on imatinib mesylate therapy in chronic myeloid leukaemia patients in a teaching hospital in Malaysia.

    Science.gov (United States)

    Bee, P C; Gan, G G; Tai, Y T; Haris, A R; Chin, E; Veera, S N

    2012-01-01

    The introduction of imatinib mesylate in 1998 has changed the management of chronic myeloid leukaemia. It is now the first-line therapy for newly diagnosed chronic myeloid leukaemia patients worldwide. However, its long-term survival benefit still needs to be established in clinical setting among Asian patients. All chronic myeloid leukaemia patients in the chronic phase who were on imatinib mesylate therapy were retrospectively reviewed. Data was collected through a review of case notes, which was then processed, managed and analysed. A total of 44 patients were included in the study. The cumulative rates of complete haematological response, major cytogenetic response and major molecular response were 93.2%, 75.0% and 34.2%, respectively. The overall survival and event-free survival at five years were 86.0% and 84.9%, respectively. 31.8% of the patients developed anaemia, 29.5% neutropenia and 27.3% thrombocytopenia. A total of 43.2% of patients developed non-haematological side effects. Higher dosage (> 600 mg) and smaller body size (< 60 kg) were risk factors for haematological side effects. Patients with major cytogenetic response and absence of thrombocytopenia had better survival. The majority of our chronic myeloid leukaemia patients did well with imatinib therapy. The adverse effects in our patients were tolerable, and no patient had to stop treatment permanently.

  1. 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

  2. Exploring chronic myeloid leukemia patients' reasons for not adhering to the oral anticancer drug imatinib as prescribed.

    Science.gov (United States)

    Eliasson, Lina; Clifford, Sarah; Barber, Nick; Marin, David

    2011-05-01

    Nonadherence has been shown to be frequent amongst chronic myeloid leukemia (CML) patients prescribed imatinib, which results in reduced clinical response and increased healthcare costs. However, little is known about the reasons why CML patients frequently do not take their imatinib as prescribed. The current study explored CML patients' experience of taking, or not taking, imatinib therapy through in-depth interviews with twenty-one patients. Their adherence had been previously measured using a medication events monitoring device. The interviews were recorded, transcribed and analysed in accordance with established techniques. Patients revealed a variety of reasons for their nonadherence. Major themes that emerged from the data were the intentional and unintentional reasons for nonadherence. Furthermore, as a result of information received from health care professionals, several patients felt inappropriately reassured that their nonadherence would not have a detrimental effect on their clinical response. Factors that seemed to favour adherence were finding ways to deal with side effects and using prompts as reminders to take the medicine. This study forms a basis on which to build future adherence research and may help to develop interventions designed to ensure that patients with CML and other cancers adhere optimally to their oral drugs treatment. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on Imatinib at Two Dose Levels

    NARCIS (Netherlands)

    Casali, P.G.; Zalcberg, J.; Cesne, A. Le; Reichardt, P.; Blay, J.Y.; Lindner, L.H.; Judson, I.R.; Schoffski, P.; Leyvraz, S.; Italiano, A.; Grunwald, V.; Pousa, A.L.; Kotasek, D.; Sleijfer, S.; Kerst, J.M.; Rutkowski, P.; Fumagalli, E.; Hogendoorn, P.; Litiere, S.; Marreaud, S.; Graaf, W.T.A. van der; Gronchi, A.; Verweij, J.

    2017-01-01

    Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from

  4. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors.

    Science.gov (United States)

    Agaram, Narasimhan P; Wong, Grace C; Guo, Tianhua; Maki, Robert G; Singer, Samuel; Dematteo, Ronald P; Besmer, Peter; Antonescu, Cristina R

    2008-10-01

    BRAF and NRAS are commonly mutated in cancer and represent the most frequent genetic events in malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT and harbor KIT mutations. Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, about 10% of the cases lack mutations in these genes. It is our hypothesis following the melanoma model that mutations in BRAF or NRAS may play a role in wild-type GIST pathogenesis. Alterations in RAS/MEK/ERK pathway may also be involved in development of imatinib resistance in GIST, particularly in tumors lacking secondary KIT or PDGFRA mutations. Imatinib-naive wild-type GISTs from 61 patients, including 15 children and 28 imatinib-resistant tumors without secondary KIT mutations were analyzed. Screening for hot spots mutations in BRAF (exons 11 and 15) and NRAS (exons 2 and 3) was performed. A BRAF exon 15 V600E was identified in 3 of 61 GIST patients, who shared similar clinical features, being 49- to 55-years-old females and having their tumors located in the small bowel. The tumors were strongly KIT immunoreactive and had a high risk of malignancy. An identical V600E BRAF mutation was also identified in one of 28 imatinib resistant GIST lacking a defined mechanism of drug resistance. In conclusion, we identified a primary BRAF V600E mutations in 7% of adult GIST patients, lacking KIT/PDGFRA mutations. The BRAF-mutated GISTs show predilection for small bowel location and high risk of malignancy. A secondary V600E BRAF mutation could represent an alternative mechanism of imatinib resistance. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset.

  5. Impact of CYP2C8*3 polymorphism on in vitro metabolism of imatinib to N-desmethyl imatinib.

    Science.gov (United States)

    Khan, Muhammad Suleman; Barratt, Daniel T; Somogyi, Andrew A

    2016-01-01

    1. Imatinib is metabolized to N-desmethyl imatinib by CYPs 3A4 and 2C8. The effect of CYP2C8*3 genotype on N-desmethyl imatinib formation was unknown. 2. We examined imatinib N-demethylation in human liver microsomes (HLMs) genotyped for CYP2C8*3, in CYP2C8*3/*3 pooled HLMs and in recombinant CYP2C8 and CYP3A4 enzymes. Effects of CYP-selective inhibitors on N-demethylation were also determined. 3. A single-enzyme Michaelis-Menten model with autoinhibition best fitted CYP2C8*1/*1 HLM (n = 5) and recombinant CYP2C8 kinetic data (median ± SD Ki = 139 ± 61 µM and 149 µM, respectively). Recombinant CYP3A4 showed two-site enzyme kinetics with no autoinhibition. Three of four CYP2C8*1/*3 HLMs showed single-enzyme kinetics with no autoinhibition. Binding affinity was higher in CYP2C8*1/*3 than CYP2C8*1/*1 HLM (median ± SD Km = 6 ± 2 versus 11 ± 2 µM, P=0.04). CYP2C8*3/*3 (pooled HLM) also showed high binding affinity (Km = 4 µM) and single-enzyme weak autoinhibition (Ki = 449 µM) kinetics. CYP2C8 inhibitors reduced HLM N-demethylation by 47-75%, compared to 0-30% for CYP3A4 inhibitors. 4. In conclusion, CYP2C8*3 is a gain-of-function polymorphism for imatinib N-demethylation, which appears to be mainly mediated by CYP2C8 and not CYP3A4 in vitro in HLM.

  6. Quantification of imatinib in human serum: validation of a high-performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring and pharmacokinetic assays

    Directory of Open Access Journals (Sweden)

    Rezende VM

    2013-08-01

    Full Text Available Vinicius Marcondes Rezende,1 Ariane Rivellis,1 Mafalda Megumi Yoshinaga Novaes,1 Dalton de Alencar Fisher Chamone,2 Israel Bendit1,21Laboratory of Tumor Biology, 2Department of Hematology, School of Medicine, University of São Paulo, São Paulo, BrazilBackground: Imatinib mesylate has been a breakthrough treatment for chronic myeloid leukemia. It has become the ideal tyrosine kinase inhibitor and the standard treatment for chronic-phase leukemia. Striking results have recently been reported, but intolerance to imatinib and noncompliance with treatment remain to be solved. Molecular monitoring by quantitative real-time polymerase chain reaction is the gold standard for monitoring patients, and imatinib blood levels have also become an important tool for monitoring.Methods: A fast and cheap method was developed and validated using high-performance liquid chromatography-mass spectrometry for quantification of imatinib in human serum and tamsulosin as the internal standard. Remarkable advantages of the method includes use of serum instead of plasma, less time spent on processing and analysis, simpler procedures, and requiring reduced amounts of biological material, solvents, and reagents. Stability of the analyte was also studied. This research also intended to drive the validation scheme in clinical centers. The method was validated according to the requirements of the US Food and Drug Administration and Brazilian National Health Surveillance Agency within the range of 0.500–10.0 µg/mL with a limit of detection of 0.155 µg/mL. Stability data for the analyte are also presented.Conclusion: Given that the validated method has proved to be linear, accurate, precise, and robust, it is suitable for pharmacokinetic assays, such as bioavailability and bioequivalence, and is being successfully applied in routine therapeutic drug monitoring in the hospital service.Keywords: imatinib, high-performance liquid chromatography-mass spectrometry, therapeutic

  7. Interferon-alpha in combination with either imatinib (Gleevec) or gefitinib (Iressa) in metastatic renal cell carcinoma: a phase II trial.

    Science.gov (United States)

    Amato, Robert J; Jac, Jaroslaw; Hernandez-McClain, Joan

    2008-06-01

    Treatments for metastatic renal cell carcinoma (MRCC) are limited. RCCs frequently overexpress epithelial growth factor receptor and express c-Kit and platelet-derived growth factor receptor-beta. Combination of interferon with tyrosine kinase inhibitors of epithelial growth factor receptor [gefitinib (Iressa)] or c-Kit and platelet-derived growth factor receptor-beta [imatinib (Gleevec)] was evaluated for efficacy and safety. Patients with MRCC received 12-week cycles of interferon [3 million units (MU) subcutaneously thrice in week 1 and 6 MU thrice weekly thereafter] and either gefitinib (500 mg daily) or imatinib (600 mg daily). The gefitinib/imatinib dose was reduced as needed owing to toxicity. The primary endpoint was objective tumor response. Secondary endpoints were time to tumor progression, overall survival, and safety. Seventeen patients were enrolled. Most had clear cell [36% (6/17)] or papillary [36% (6/17)] tumors. Most (n=14) were treated on the gefitinib arm, including two patients who crossed over from the imatinib arm after experiencing disease progression. Objective tumor responses were evaluable in 14 patients (82%). Of these 14, partial responses occurred in three (21%), stable disease in seven (50%), and progressive disease in four (29%). The most frequent treatment-related adverse events were skin rash, flu-like symptoms, and fatigue (both treatment arms); diarrhea (gefitinib arm only); and thrombocytopenia and leukopenia (imatinib arm only). Median time to tumor progression (range) for patients on the gefitinib arm only was 4.27 (1.13-15.97) months and median overall survival (range) was 11.42+ (1.13-29.07+) months. Combination of gefitinib with interferon safely delays progression of refractory MRCC. Further studies in this setting are warranted.

  8. Long-term outcomes of nilotinib treatment for chonic myelogenous leukemia patients with imatinib resistance or intolerance%尼洛替尼治疗伊马替尼耐药或不耐受的慢性粒细胞白血病的长期随访研究

    Institute of Scientific and Technical Information of China (English)

    魏永强; 张贤; 陈伟伟; 曹睿; 阴常欣; 冯茹; 刘启发; 孟凡义

    2012-01-01

    目的 评价对伊马替尼耐药或不耐受的慢性粒细胞白血病(CML)患者接受尼洛替尼治疗的远期疗效和安全性.方法 26例对伊马替尼耐药或不耐受CML患者接受尼洛替尼400~800 mg/d治疗,随访观察近5年,定期监测血液学、细胞遗传学及分子生物学指标,记录用药后患者临床表现及各项生化指标,评价其疗效、不良反应.结果 26例对伊马替尼耐药或不耐受的CML患者,尼洛替尼中位治疗时间17个月,中位随访时间51个月.累计获得完全血液学缓解(CHR)16例(61.5%),获得主要细胞遗传学缓解(MCyR)13例(50.0%),获得完全细胞遗传学缓解(CCyR)9例(34.6%),获得主要分子生物学缓解(MMR)7例(26.9%).尼洛替尼治疗相关的非血液学不良反应多为1~2级,主要为胆红素升高(69 2%)和皮疹(57 7%).3~4级血液学不良反应包括血小板减少(53.8%)、中性粒细胞减少和贫血(分别为26.9%和19.2%).相比进展期患者,尼洛替尼对慢性期和缓解期的患者疗疗效更佳、血液学副作用更少.结论 尼洛替尼为对伊马替尼耐药和不耐受的CML患者提供了一个有效并安全的治疗选择,尤其对非进展期CML患者更为安全和有效.%Objective To evaluate the long-term clinical efficacy and safety of nilotinib in the treatment of chronic myelogenous leukemia (CML) patients with imatinib resistance or intolerance. Methods Twenty-six CML patients with imatinib resistance or intolerance received nilotinib treatment at the dose of 400 mg once or twice daily. The patients were followed up for nearly 5 years with regular monitoring of the hematologic, cytogenetic and molecular biological markers and recording of the clinical manifestations and biochemical indicators to evaluate the therapeutic effect and adverse events. Results The median duration of nilotinib therapy was 17 (1-56) months, and the patients were follow up for a median of 51 months. At the last follow-up, 16

  9. Imatinib treatment of chronic myeloid leukemia in chronic phase: clinical effect assessment of 69 cases%伊马替尼治疗69例慢性粒细胞白血病慢性期患者的临床效果评价

    Institute of Scientific and Technical Information of China (English)

    钟敏; 苏群豪; 胡敏; 陶石

    2015-01-01

    目的:评价慢性粒细胞白血病慢性期患者接受伊马替尼治疗的临床效果及不良反应.方法:慢性粒细胞白血病慢性期患者114例,随机分为观察组(69例)和对照组(45例)两组.观察组患者采用伊马替尼进行治疗,对照组则采用干扰素进行治疗,对比两组患者的临床治疗效果.结果:观察组患者治疗3个月完全血液学缓解率(95.65%)、6个月部分细胞遗传学缓解率(82.61%)、12个月完全细胞遗传学缓解率(79.71%)、18个月主要分子学缓解率(68.12%)与对照组(75.55%、33.33%、22.22%、0%)比较差异具有统计学意义(P<0.05).两组不良反应比较,观察组的不良反应较轻,安全性要高于对照组,差异具有统计学意义(P<0.05).观察组五年的总生存率为97.10%,无事件生存率为91.30%,与对照组的82.22%、73.33%比较,差异具有统计学意义(P<0.05).结论:伊马替尼治疗能明显提高慢性粒细胞白血病慢性期患者的细胞遗传学和分子学疗效,不良反应少,可延长无疾病进展生存期.%Objective: To investigate the clinical effect imatinib treatment of patients with chronic myeloid leukemia in chronic phase. Methods: 114 patients with chronic myeloid leukemia in chronic phase were randomly divided into an observation group (69 cases) and a control group (45 cases). The observation group was treated with imatinib and the control group was treated with interferon. The clinical treatment effect of the two groups was compared. Results: Regarding the observation group, the rate of the complete hematologic response (CHR) of patients treated for 3 months was 95.65%, the rate of the part cytogenetic response (PCyR) of patients treated for 6 months was 82.61%, the rate of the complete cytogenetic response (CCyR) of patients treated for 12 months was 79.71%, and the rate of the main molecular response (MMR) was 68.12%. Regarding the control group, the rate of the complete hematologic response, the part cytogenetic

  10. Antiproliferation effect of imatinib mesylate on MCF7, T-47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR-β, PDGF-BB, c-Kit and SCF genes

    Science.gov (United States)

    Kadivar, Ali; Kamalidehghan, Behnam; Akbari Javar, Hamid; Karimi, Benyamin; Sedghi, Reihaneh; Noordin, Mohamed Ibrahim

    2017-01-01

    Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF). The MTS assay was conducted in therapeutic relevant concentration of 2–10 µM for 96, 120 and 144 h treatment. In addition, apoptosis induction and cytostatic activity of imatinib mesylate were investigated with the terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL and cell cycle assays, respectively, in a time-dependent manner. Comparative real-time PCR and Western blot analysis were conducted to evaluate the expression and regulation of imatinib target genes and proteins. Our finding revealed that imatinib mesylate antiproliferation effect, apoptosis induction and cytostatic activity were significantly higher in breast cancer cell lines compared to MCF 10A. This effect might be due to the expression of PDGFR-β, PDGF-BB, c-Kit and SCF, which was expressed by all examined cell lines, except the T-47D cell line which was not expressed c-Kit. However, examined gene and proteins expressed more in cancer cell lines. Therefore, imatinib mesylate was more effective on them. It is concluded that imatinib has at least two potential targets in both examined breast cancer cell lines and can be a promising drug for targeted therapy to treat breast cancer. PMID:28260860

  11. 老年冠心病患者介入治疗术前心理分析与护理措施%Preoperative psychoanalysis and nursing measures of senior patients with coronary heart disease in intervening treatment

    Institute of Scientific and Technical Information of China (English)

    李琼; 尹艳; 金葵花; 袁琰琴; 刘群

    2003-01-01

    @@ BACKGROUND:The intervening treatment of senior patients with coronary heart disease is more and more.It is important of preoperative psychoanalysis and nursing measures for the patients according to natural characteristics,educational extent and knowledge of diseases of senior patients.

  12. Phase I clinical trial of combination imatinib and ipilimumab in patients with advanced malignancies

    OpenAIRE

    Reilley, Matthew J.; Bailey, Ann; Subbiah, Vivek; Janku, Filip; Naing, Aung; Falchook, Gerald; Karp, Daniel; Piha-Paul, Sarina; Tsimberidou, Apostolia; Fu, Siqing; Lim, JoAnn; Bean, Stacie; Bass, Allison; Montez, Sandra; Vence, Luis

    2017-01-01

    Background Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. Methods Primary objective of the dose-escalation study (3?+?3 design) was to establish the maximu...

  13. Preoperative Y-90 microsphere selective internal radiation treatment for tumor downsizing and future liver remnant recruitment: a novel approach to improving the safety of major hepatic resections

    Directory of Open Access Journals (Sweden)

    Gulec Seza A

    2009-01-01

    Full Text Available Abstract Background Extended liver resections are being performed more liberally than ever. The extent of resection of liver metastases, however, is restricted by the volume of the future liver remnant (FLR. An intervention that would both accomplish tumor control and induce compensatory hypertrophy, with good patient tolerability, could improve clinical outcomes. Case presentation A 53-year-old woman with a history of cervical cancer presented with a large liver mass. Subsequent biopsy indicated poorly differentiated carcinoma with necrosis suggestive of squamous cell origin. A decision was made to proceed with pre-operative chemotherapy and Y-90 microsphere SIRT with the intent to obtain systemic control over the disease, downsize the hepatic lesion, and improve the FLR. A surgical exploration was performed six months after the first SIRT (three months after the second. There was no extrahepatic disease. The tumor was found to be significantly decreased in size with central and peripheral scarring. The left lobe was satisfactorily hypertrophied. A formal right hepatic lobectomy was performed with macroscopic negative margins. Conclusion Selective internal radiation treatment (SIRT with yttrium-90 (Y-90 microspheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio. We present this case report to suggest that the portal vein radiation dose can be substantially increased with the intent of inducing portal/periportal fibrosis. Such a therapeutic manipulation in lobar Y-90 microsphere treatment could accomplish the end points of PVE with avoidance of the concern regarding tumor progression.

  14. Dose cone-beam CT alter treatment plans? Comparison of preoperative implant planning using panoramic versus cone-beam CT images

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero, Maria Eugenia; Jacobs, Reinhilde [Dept. of Oral and Maxillofacial Surgery, University Hospitals, Leuven (Belgium); Norge, Jorge; Castro, Carmen [Master of Periodontology, Universidad San Martin de Porres, Lima (Peru)

    2014-06-15

    The present study was performed to compare the planning of implant placement based on panoramic radiography (PAN) and cone-beam computed tomography (CBCT) images, and to study the impact of the image dataset on the treatment planning. One hundred five partially edentulous patients (77 males, 28 females, mean age: 46 years, range: 26-67 years) seeking oral implant rehabilitation were referred for presurgical imaging. Imaging consisted of PAN and CBCT imaging. Four observers planned implant treatment based on the two-dimensional (2D) image datasets and at least one month later on the three-dimensional (3D) image dataset. Apart from presurgical diagnostic and dimensional measurement tasks, the observers needed to indicate the surgical confidence levels and assess the image quality in relation to the presurgical needs. All observers confirmed that both imaging modalities (PAN and CBCT) gave similar values when planning implant diameter. Also, the results showed no differences between both imaging modalities for the length of implants with an anterior location. However, significant differences were found in the length of implants with a posterior location. For implant dimensions, longer lengths of the implants were planned with PAN, as confirmed by two observers. CBCT provided images with improved scores for subjective image quality and surgical confidence levels. Within the limitations of this study, there was a trend toward PAN-based preoperative planning of implant placement leading towards the use of longer implants within the posterior jaw bone.

  15. Combination of imatinib with CXCR4 antagonist BKT140 overcomes the protective effect of stroma and targets CML in vitro and in vivo.

    Science.gov (United States)

    Beider, Katia; Darash-Yahana, Merav; Blaier, Orly; Koren-Michowitz, Maya; Abraham, Michal; Wald, Hanna; Wald, Ori; Galun, Eithan; Eizenberg, Orly; Peled, Amnon; Nagler, Arnon

    2014-05-01

    Functional role of CXCR4 in chronic myelogenous leukemia (CML) progression was evaluated. Elevated CXCR4 significantly increased the in vitro survival and proliferation in response to CXCL12. CXCR4 stimulation resulted in activation of extracellular signal-regulated kinase (Erk)-1/2, Akt, S6K, STAT3, and STAT5 prosurvival signaling pathways. In accordance, we found that in vitro treatment with CXCR4 antagonist BKT140 directly inhibited the cell growth and induced cell death of CML cells. Combination of BKT140 with suboptimal concentrations of imatinib significantly increased the anti-CML effect. BKT140 induced apoptotic cell death, decreasing the levels of HSP70 and HSP90 chaperones and antiapoptotic proteins BCL-2 and BCL-XL, subsequently promoting the release of mitochondrial factors cytochrome c and SMAC/Diablo. Bone marrow (BM) stromal cells (BMSC) markedly increased the proliferation of CML cells and protected them from imatinib-induced apoptosis. Furthermore, BMSCs elevated proto-oncogene BCL6 expression in the CML cells in response to imatinib treatment, suggesting the possible role of BCL6 in stroma-mediated TKI resistance. BKT140 reversed the protective effect of the stroma, effectively promoted apoptosis, and decreased BCL6 levels in CML cells cocultured with BMSCs. BKT140 administration in vivo effectively reduced the growth of subcutaneous K562-produced xenografts. Moreover, the combination of BKT140 with low-dose imatinib markedly inhibited tumor growth, achieving 95% suppression. Taken together, our data indicate the importance of CXCR4/CXCL12 axis in CML growth and CML-BM stroma interaction. CXCR4 inhibition with BKT140 antagonist efficiently cooperated with imatinib in vitro and in vivo. These results provide the rational basis for CXCR4-targeted therapy in combination with TKI to override drug resistance and suppress residual disease.

  16. Imatinib in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB in chronic or blast phase.

    Science.gov (United States)

    Jawhar, Mohamad; Naumann, Nicole; Schwaab, Juliana; Baurmann, Herrad; Casper, Jochen; Dang, Tu-Anh; Dietze, Lutz; Döhner, Konstanze; Hänel, Annette; Lathan, Bernd; Link, Hartmut; Lotfi, Sina; Maywald, Ole; Mielke, Stephan; Müller, Lothar; Platzbecker, Uwe; Prümmer, Otto; Thomssen, Henrike; Töpelt, Karin; Panse, Jens; Vieler, Tom; Hofmann, Wolf-Karsten; Haferlach, Torsten; Haferlach, Claudia; Fabarius, Alice; Hochhaus, Andreas; Cross, Nicholas C P; Reiter, Andreas; Metzgeroth, Georgia

    2017-09-01

    We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10(9)/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1-135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia, (c) presentation in chronic or blast phase, (d) rapid responses and long-term remission on low-dose imatinib, and (e) possible adverse prognostic impact of a complex karyotype.

  17. Dasatinib treatment based on BCR-ABL mutation detection in imatinib-resistant patients with chronic myeloid leukemia%BCR-ABL突变检测指导下的达沙替尼治疗伊马替尼耐药的慢性髓性白血病疗效分析

    Institute of Scientific and Technical Information of China (English)

    江倩; 秦亚溱; 赖悦云; 江浩; 石红霞

    2016-01-01

    Objective To evaluate the efficiency of dasatinib as the second-or third-line tyrosine kinase inhibitor(TKI)in imatinib-resistant patients with chronic myeloid leukemia(CML)based on BCR-ABL mutation detection. Methods 122 CML patients received dasatinib treatment, including 83 with imatinib-resistance and 39 with both imatinib-and nilotinib-resistance, 55 in the chronic-phase(CP), 21 in the accelerated-phase (AP) and 46 in the blast-phase (BP). Those harboring dasatinib highly-resistant mutations(T315I/A, F317L/V/C and V299L)were excluded based on BCR-ABL kinase domain mutation screening by Sanger sequencing at baseline. Hematologic, cytogenetic and molecular responses were evaluated regularly, and rates of progression-free-survival(PFS)and overall survival(OS)were analyzed. BCR-ABL mutation detection was performed once the patients failed on dasatinib. Results In the CP patients, the rates of complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response(MMR)and molecular response 4.5(MR4.5)were 92.7%, 53.7%, 29.6%and 14.8%, respectively. 4-year PFS and OS rates were 84.4%and 89.5%, respectively. In the AP patients, HR and CCyR rates were 81.0%and 35.0%;and 3-year PFS and OS rates were 56.1%and 59.3%, respectively. In the BP patients, HR and CCyR rates were 63.0%and 21.4%;and 1-year PFS and OS rates were 43.6%and 61.8%, respectively. Outcomes were similar when dasatinib was used as the second-line TKI or thethird-line TKI. Of the 75 patients who were resistant to dasatinib, 37(48.7%)developed new mutation(s), and T315I(59.5%)was the most common mutation type. The patients who already harbored mutation(s) before dasatinib therapy achieved similar responses and outcomes to those with no mutation at baseline. However, they had higher likelihood of developing additional mutations associated with resistance to dasatinib(65.7%vs 34.1%, P=0.006). Conclusions Dasatinib was proved to be effective in the treatment of imatinib

  18. Renal dysfunction in a renal transplant patient treated concurrently with cyclosporine and imatinib.

    Science.gov (United States)

    Mulder, Karen E; Egorin, Merrill J; Sawyer, Michael B

    2012-12-01

    Imatinib mesylate has proven activity in treating locally advanced or metastatic gastrointestinal stromal tumors (GIST). Drug interactions are particularly concerning as imatinib is extensively metabolized by the cytochrome P450 enzyme system. We describe the clinical course of a 72 year-old male with a cadaveric renal transplant requiring cyclosporine that presented with a metastatic GIST and was started on imatinib at the standard dose of 400 mg daily. Imatinib initiation resulted in a decline in renal function with the serum creatinine increasing from 123 μmol/L to 196 μmol/L and an elevation in whole blood cyclosporine concentrations from 79 μg/L to 139 μg/L. No other imatinib toxicities were reported. With discontinuation of imatinib, the serum creatinine returned to baseline as did the whole blood cyclosporine levels. Ultimately, decreasing both the cyclosporine and imatinib dosing was associated with stabilized renal function (serum creatinine 150-186 μmol/L) and cyclosporine concentrations (53-97 μg/L). A prolonged partial response to therapy for 19 months was maintained despite low imatinib trough concentrations measured on two separate occasions (127.1 ng/ml and 139 ng/ml). In our patient, imatinib initiation resulted in renal toxicity most likely due to its interaction with cyclosporine resulting in elevation of the whole blood cyclosporine concentration.

  19. Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl

    Directory of Open Access Journals (Sweden)

    Cao Qi

    2010-05-01

    Full Text Available Abstract Background Chronic myelogenous leukemia (CML is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I. Results In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5 or imatinib-resistant (KBM5-T315I CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways. Conclusion To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for

  20. Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

    Directory of Open Access Journals (Sweden)

    Bassam Francis Matti

    2013-12-01

    Full Text Available OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML. During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years. The study showed that the commonest hematological side effects were grade 2 anemia (12.5% followed by leukopenia (8% and thrombocytopenia (4%, while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%, followed by musculoskeletal pain (35.5%, then gastro-intestinal symptoms (vomiting, diarrhea (19%. Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.

  1. Mechanically assisted 3D ultrasound for pre-operative assessment and guiding percutaneous treatment of focal liver tumors

    Science.gov (United States)

    Sadeghi Neshat, Hamid; Bax, Jeffery; Barker, Kevin; Gardi, Lori; Chedalavada, Jason; Kakani, Nirmal; Fenster, Aaron

    2014-03-01

    Image-guided percutaneous ablation is the standard treatment for focal liver tumors deemed inoperable and is commonly used to maintain eligibility for patients on transplant waitlists. Radiofrequency (RFA), microwave (MWA) and cryoablation technologies are all delivered via one or a number of needle-shaped probes inserted directly into the tumor. Planning is mostly based on contrast CT/MRI. While intra-procedural CT is commonly used to confirm the intended probe placement, 2D ultrasound (US) remains the main, and in some centers the only imaging modality used for needle guidance. Corresponding intraoperative 2D US with planning and other intra-procedural imaging modalities is essential for accurate needle placement. However, identification of matching features of interest among these images is often challenging given the limited field-of-view (FOV) and low quality of 2D US images. We have developed a passive tracking arm with a motorized scan-head and software tools to improve guiding capabilities of conventional US by large FOV 3D US scans that provides more anatomical landmarks that can facilitate registration of US with both planning and intra-procedural images. The tracker arm is used to scan the whole liver with a high geometrical accuracy that facilitates multi-modality landmark based image registration. Software tools are provided to assist with the segmentation of the ablation probes and tumors, find the 2D view that best shows the probe(s) from a 3D US image, and to identify the corresponding image from planning CT scans. In this paper, evaluation results from laboratory testing and a phase 1 clinical trial for planning and guiding RFA and MWA procedures using the developed system will be presented. Early clinical results show a comparable performance to intra-procedural CT that suggests 3D US as a cost-effective alternative with no side-effects in centers where CT is not available.

  2. Observation on the therapeutic effects of imatinib mesylate in treatment of 43 cases with advanced chronic myelogenous leukemia%甲磺酸伊马替尼治疗43例慢性粒细胞白血病进展期患者的疗效观察

    Institute of Scientific and Technical Information of China (English)

    朱晓明; 程辉; 游泳

    2013-01-01

    目的:探讨甲磺酸伊马替尼(STI571,格列卫)治疗慢性粒细胞白血病(CML)进展期(即加速期、急变期)患者的临床疗效.方法:43例疾病进展期CML患者口服格列卫治疗,评价其血液学、细胞遗传学及分子遗传学疗效.结果:43例患者的完全血液学反应(CHR)率、完全细胞遗传学反应(CCyR)率和完全分子遗传学反应(CMR)率分别为44.2%、30.0%和21.9%,观察期内总病死率为25.6%,均于12个月内死亡,不同年龄(≤25岁,>25岁)患者之间病死率有统计学意义(P<0.05).结论:格列卫对慢性粒细胞白血病进展期患者有一定的疗效,但耐药现象较普遍,年轻患者的预后可能较差.%Objective: To investigate the effects of imatinib mesylate in treatment of advanced chronic myelogenous leukemia. Methods: To observe the hematologic, cytogenetic and molecular genetic effect of Gleevic in treatment of 43 cases with advanced chronic myelogenous leukemia. Results; The complete hematologic response, complete cytogenetic response and complete molecular genetic response was 44. 2% , 30. 0% and 21. 9% , respectively. Total mortality during observation was 25.6% , and those were dead in 12 months. There was statistically difference in different ages ( ≤25 yeas and >25 years). Conclusions; Gleevic had effects in patients with advanced chronic myelogenous leukemia, but the drug resistance is common, and young patients might have bad prognosis.

  3. Berbamine exhibits potent antitumor effects on imatinib-resistant CML cells in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Yan-lin WEI; Lei XU; Yun LIANG; Xiao-hua XU; Xiao-ying ZHAO

    2009-01-01

    Aim: The aim of this study was to explore the effects and mechanism of berbamine on imatinib-resistant BCR-ABL-positive human leukemia K562 (K562-r) cells in vitro and in vivo. Methods: Cell viability was measured by MTT assay, and apoptotic morphology changes were detected by fluorescence microscopy. The apoptosis rate was measured by flow cytometric assay, mdr-1 mRNA levels were determined by RT-PCR. Bcl-2 family proteins, cytochrome c( cyt C), poly (ADP-ribose) polymerase (PARP), and P-glycoprotein were detected by Western blot. BALB/c nu/nu mice were injected with K562-r ceils subcutaneously. Tumor-bearing mice were treated intravenously with berbamine.Results: MTT tests revealed that berbamine significantly inhibited K562-r cell proliferation and increased the chemo-sensitivity of Kf62-r cells to imatirtib. The apoptosis rate was significantly increased following treatment with 21.2 μmol/L berbamine; formation of typical apoptotic blebs was apparent, as observed by fluorescence microscopy. Expression levels of mdr-1 mRNA and P-gp protein were high in untreated K562-r cells and significantly down-regulated by berbamine treatment. Berbamine-treated K562-r cells also exhibited down-regulated expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, up-regulated expression of the apoptotic proteins Box and cytoplasmic cyt C, and stimulated proteolytic cleavage of PARP. In addition, berbamine also suppressed the growth of K562-r xenotransplanted tumors in vivo. Conclusion: Berbamine inhibited proliferation of K562-r cells both in vitro and in vivo. Berbamine-induced apoptosis in K562-r cells appeared to occur through a mechanism involving Bcl-2 family proteins, as well as mdr-1 mRNA and P-gp pro- tein. 13erbamine in combination with imatirtib restored the chemo-sensitivity of K562-r cells to imatinib. Our findings sug-gest that berbamine may be useful in treating imatinib-resistant CML patients.

  4. Low doses of imatinib induce myelopoiesis and enhance host anti-microbial immunity.

    Directory of Open Access Journals (Sweden)

    Ruth J Napier

    2015-03-01

    Full Text Available Imatinib mesylate (Gleevec inhibits Abl1, c-Kit, and related protein tyrosine kinases (PTKs and serves as a therapeutic for chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib also has efficacy against various pathogens, including pathogenic mycobacteria, where it decreases bacterial load in mice, albeit at doses below those used for treating cancer. We report that imatinib at such low doses unexpectedly induces differentiation of hematopoietic stem cells and progenitors in the bone marrow, augments myelopoiesis but not lymphopoiesis, and increases numbers of myeloid cells in blood and spleen. Whereas progenitor differentiation relies on partial inhibition of c-Kit by imatinib, lineage commitment depends upon inhibition of other PTKs. Thus, imatinib mimics "emergency hematopoiesis," a physiological innate immune response to infection. Increasing neutrophil numbers by adoptive transfer sufficed to reduce mycobacterial load, and imatinib reduced bacterial load of Franciscella spp., which do not utilize imatinib-sensitive PTKs for pathogenesis. Thus, potentiation of the immune response by imatinib at low doses may facilitate clearance of diverse microbial pathogens.

  5. Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with imatinib mesylate against chronic myelogenous leukemia cell lines

    Directory of Open Access Journals (Sweden)

    Xin P

    2017-04-01

    Full Text Available Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu Department of Haematology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Licheng, Quanzhou, Fujian Province, China Background: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML cells and sensitivity of tyrosine kinase inhibitor in vitro.Methods: Two human CML cell lines, K562 and KBM7R (T315I mutant strain, were used. The proliferation of CML cells was detected by MTS (Owen’s reagent assay. Cell cycle and apoptosis assay were examined by flow cytometric analysis. The phosphorylation levels and the expression levels were both evaluated by Western blot analysis. NVP-BEZ235 in combination with imatinib was also used to reveal the effect on proliferation and apoptosis.Results: NVP-BEZ235 significantly inhibited the proliferation in a time- and dose-dependent manner, and the half-maximal inhibitory concentration values of NVP-BEZ235 inhibiting the proliferation of K562 and KBM7R were 0.37±0.21 and 0.43±0.27 µmol/L, respectively, after 48 h. Cell apoptosis assay showed that NVP-BEZ235 significantly increased the late apoptotic cells. Cell cycle analysis indicated that the cells were mostly arrested in G1/G0 phase after treatment by NVP-BEZ235. In addition, results also found that, after treatment by NVP-BEZ235, phosphorylation levels of Akt kinase and S6K kinase significantly reduced, and the expression levels of cleaved caspase-3 significantly increased; meanwhile, the expression levels of caspase-3, B-cell lymphoma-2, cyclin D1, and cyclin D2 significantly decreased, and the ratio of LC3II/LC3I was significantly increased with increased LC3II expression level. Moreover, imatinib in combination with NVP-BEZ235

  6. Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones:Results of a retrospective,single center study between 1996-2002

    Institute of Scientific and Technical Information of China (English)

    Gabor Mester; Gyorgy Reti; Attila Nagy; Peter Laszlo Lakatos

    2004-01-01

    AIM: The optimal treatment for bile duct stones (in terms of cost, complications and accuracy) is unclear. The aim of our study was to determine the predictive factors for preoperative endoscopic retrograde cholangiopancreatography (ERCP).METHODS: Patients undergoing preoperative ERCP (≤90 dbefore laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1st of January 1996 to the 31st of December 2002. The indications for ERCP were elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct (≥8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and the combination of factors were compared to the result of ERCP.RESULTS: Two hundred and six preoperative ERCPs were performed during the observed period. The rate of successful cannulation for ERC was (97.1%). Bile duct stones were detected in 81 patients (39.3%), and successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones. The positive predictive value for one prognostic factor was 1.2%, for two 43%,for three 72.5%, for four or more 91.4%.CONCLUSION: Based on our data preoperative ERCP is highly recommended in patients with three or more positive factors (high risk patients). In contrast, ERCP is not indicated in patients with zero or one factor (low risk patients).Preoperative ERCP should be offered to patients with two positive factors (moderate risk patients), however the practice should also be based on the local conditions (e.g.skill of the endoscopist, other diagnostic tools).

  7. Medical approach to the treatment of feline injection site sarcoma with masitinib: a case report

    Directory of Open Access Journals (Sweden)

    Ledoux JM

    2014-09-01

    Full Text Available Jean-Marie Ledoux,1 Pascal Brun,2 Tom Chapuis,2 Paul Dumas,3 Jean Guillotin41Veterinary Surgery, Lys-Lez-Lannoy, 2AB Science, Paris, 3Laboratoire de Pathologie Vétérinaire du Nord, Annœullin, 4Laboratoire Départemental Public, Villeneuve d'Ascq, FranceAbstract: Feline injection site sarcoma is a common tumor among cats, for which existing medical treatments do not prove to be entirely satisfactory. In this tumor, the platelet-derived growth factor receptor, a tyrosine kinase receptor, is frequently hyperactivated. In the past, clinical case reports with imatinib, a tyrosine kinase inhibitor (TKI, have demonstrated tumoral stabilization. Here we describe the use of another TKI, masitinib, which specifically inhibits c-Kit, platelet-derived growth factor receptor, and Lyn, and is currently licensed for veterinary use in canine mast cell tumors. The therapeutic results were initially satisfactory, with regression of the tumor followed by tumoral recurrence which was stabilized and moderately reduced. Further studies are suggested, in order to evaluate the relevance of TKIs in the treatment and prevention of recurrences of feline injection site sarcoma. Tumoral stabilization by means of an inexpensive and reasonably well tolerated treatment would prove to be of true therapeutic relevance, in particular for inoperable feline injection site sarcomas. Another indication for such TKIs could be in preoperative treatment as a means of facilitating surgical excision by reduction of adhesions.Keywords: fibrosarcoma, imatinib, platelet-derived growth factor receptor, tyrosine kinase receptor

  8. Regulatory network analysis of microRNAs and genes in imatinib-resistant chronic myeloid leukemia.

    Science.gov (United States)

    Soltani, Ismael; Gharbi, Hanen; Hassine, Islem Ben; Bouguerra, Ghada; Douzi, Kais; Teber, Mouheb; Abbes, Salem; Menif, Samia

    2016-09-16

    Targeted therapy in the form of selective breakpoint cluster region-abelson (BCR/ABL) tyrosine kinase inhibitor (imatinib mesylate) has successfully been introduced in the treatment of the chronic myeloid leukemia (CML). However, acquired resistance against imatinib mesylate (IM) has been reported in nearly half of patients and has been recognized as major issue in clinical practice. Multiple resistance genes and microRNAs (miRNAs) are thought to be involved in the IM resistance process. These resistance genes and miRNAs tend to interact with each other through a regulatory network. Therefore, it is crucial to study the impact of these interactions in the IM resistance process. The present study focused on miRNA and gene network analysis in order to elucidate the role of interacting elements and to understand their functional contribution in therapeutic failure. Unlike previous studies which were centered only on genes or miRNAs, the prime focus of the present study was on relationships. To this end, three regulatory networks including differentially expressed, related, and global networks were constructed and analyzed in search of similarities and differences. Regulatory associations between miRNAs and their target genes, transcription factors and miRNAs, as well as miRNAs and their host genes were also macroscopically investigated. Certain key pathways in the three networks, especially in the differentially expressed network, were featured. The differentially expressed network emerged as a fault map of IM-resistant CML. Theoretically, the IM resistance process could be prevented by correcting the included errors. The present network-based approach to study resistance miRNAs and genes might help in understanding the molecular mechanisms of IM resistance in CML as well as in the improvement of CML therapy.

  9. The effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Yeliz Yilmaz

    2016-08-01

    Conclusion: Preoperative Lugol solution treatment was found to be a significant independent determinant of intraoperative blood loss. Moreover, preoperative Lugol solution treatment decreased the rate of blood flow, and intraoperative blood loss during thyroidectomy.

  10. Preoperative preparation of children

    Directory of Open Access Journals (Sweden)

    Priya Reshma Aranha

    2017-01-01

    Full Text Available Surgery is a stressful and anxiety provoking experience for children. Millions of children undergo surgery every year. The majority of children experience significant preoperative anxiety which intern can affect their recovery. Preoperative anxiety may bring about physical and physiological changes in children, which can be particularly evident in terms of increased heart rate and blood pressure. To identify various strategies used to minimize the preoperative anxiety of children and update their clinical effectiveness among children undergoing surgery, the authors searched PubMed, MEDLINE, CINAHL, ScienceDirect, Google Scholar, Scopus, and Cochrane Library for identifying the relevant studies and retrieved available literature. It is concluded that utilization of the strategies available to reduce the preoperative anxiety of children will be a promising intervention to reduce anxiety, to promote relaxation, satisfaction, and speedy recovery. Many of these techniques are simple, cost-effective and can be easily carried out by nurses. It is essential to use the age appropriate and individualized methods in preparing children for surgery. Further research is required to strengthen the evidence.

  11. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study.

    Science.gov (United States)

    Baccarani, Michele; Druker, Brian J; Branford, Susan; Kim, Dong-Wook; Pane, Fabrizio; Mongay, Lidia; Mone, Manisha; Ortmann, Christine-Elke; Kantarjian, Hagop M; Radich, Jerald P; Hughes, Timothy P; Cortes, Jorge E; Guilhot, François

    2014-01-01

    The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival(PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR.Adverse events were more frequent with high-dose imatinib. Patients with B1 treatment interruption (vs [1) and those able to maintain imatinib C600 mg/day (vs\\600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with longterm clinical outcomes.

  12. [Successful induction of complete cytogenetic response with low-dose imatinib mesylate in an accelerated phase chronic myelogenous leukemia patient who developed severe bone marrow aplasia following standard-dose imatinib mesylate therapy].

    Science.gov (United States)

    Nakazato, Tomonori; Suzuki, Kazuhito; Mihara, Ai; Sanada, Yukinari; Kakimoto, Tsunayuki

    2010-03-01

    A 58-year-old female presented with massive splenomegaly, leukocytosis and anemia. Bone marrow appearance was consistent with CML-AP, and t (9;22) (q34;q11) was detected on karyotyping. 600 mg daily imatinib mesylate (imatinib) was started and achieved complete hematological remission. However, pancytopenia was evident. Despite dose reduction and subsequent drug withdrawal, the pancytopenia worsened and she became transfusion dependent. Grade 4 pancytopenia persisted for 8 months after discontinuing imatinib. Bone marrow biopsy showed severe bone marrow aplasia with no morphological evidence of disease progression. Karyotyping showed minor cytogenetic response with no clonal evolution. Signs of hematological recovery appeared 8 months after stopping imatinib. The patient was re-started on imatinib at a dose of 100 mg/day. The dose was increased to 200 mg/day without hematological toxicity. Complete cytogenetic response (CCyR) was achieved 5 months after the re-administration of imatinib. The patient maintained CCyR with 200 mg of imatinib per day. Prolonged severe bone marrow aplasia has rarely been reported as a complication of imatinib therapy. This case also suggests that low-dose imatinib would be tolerable and effective for some CML patients who are intolerant of a standard dose of imatinib.

  13. Twin pregnancy in a patient of chronic myeloid leukemia on imatinib therapy.

    Science.gov (United States)

    Meera, V; Jijina, Farah; Shrikande, Mitu; Madkaikar, Manisha; Ghosh, K

    2008-10-01

    Imatinib is a tyrosine kinase inhibitor and is now used regularly in chronic myeloid leukaemia therapy in chronic phase with great success. This drug due its very nature of action is suspected to be teratogenic hence the patients are counseled not to get pregnant while on this drug. However in world literature few normal pregnancies have been reported in patients on Imatinib therapy, though no twin pregnancy has been reported on this medication. We report here the birth of normal mono-ovular mono-chorionic twin while the patient is on imatinib during conception and early pregnancy for chronic myeloid leukaemia.

  14. In vitro effect of imatinib mesylate loaded on polybutylcyanoacrylate nanoparticles on leukemia cell line K562.

    Science.gov (United States)

    Hasandoost, Leyla; Akbarzadeh, Azim; Attar, Hossein; Heydarinasab, Amir

    2017-05-01

    The study aimed to prepare imatinib mesylate-loaded polybutylcyanoacrylate (PBCA) nanoparticles and evaluate their efficacy on leukemia cell line K562. The formulation was prepared by miniemulsion polymerization technique. Nanoparticles were characterized by dynamic light scattering (DLS), spectrophotometry, Fourier transform infrared spectroscopy (FTIR), dialysis membrane, and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) techniques. Nanoscale particles with high encapsulation efficiency (86%) and physical entrapment of drug were observed. In addition, nanoparticles showed suitable drug retention capability and potentiate the cytotoxicity effects of imatinib mesylate. Findings of study suggested PBCA nanoparticles are promising carrier for imatinib mesylate delivery to leukemia cell line K562.

  15. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Møller, A; Villebro, N

    2005-01-01

    Smokers have a substantially increased risk of intra- and postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence. The preoperative period may be a well chosen time to offer smoking cessation interventions due to increased patient motivation....

  16. S-1-Based versus capecitabine-based preoperative chemoradiotherapy in the treatment of locally advanced rectal cancer: a matched-pair analysis.

    Directory of Open Access Journals (Sweden)

    Meng Su

    Full Text Available OBJECTIVE: The aim of this paper was to compare the efficacy and safety of S-1-based and capecitabine-based preoperative chemoradiotherapy regimens in patients with locally advanced rectal cancer through a retrospective matched-pair analysis. MATERIALS AND METHODS: Between Jan 2010 and Mar 2014, 24 patients with locally advanced rectal cancer who received preoperative radiotherapy concurrently with S-1 were individually matched with 24 contemporary patients with locally advanced rectal cancer who received preoperative radiotherapy concurrently with capecitabine according to clinical stage (as determined by pelvic magnetic resonance imaging and computed tomography and age (within five years. All these patients performed mesorectal excision 4-8 weeks after the completion of chemoradiotherapy. RESULTS: The tumor volume reduction rates were 55.9±15.1% in the S-1 group and 53.8±16.0% in the capecitabine group (p = 0.619. The overall downstaging, including both T downstaging and N downstaging, occurred in 83.3% of the S-1 group and 70.8% of the capecitabine group (p = 0.508. The significant tumor regression, including regression grade I and II, occurred in 33.3% of S-1 patients and 25.0% of capecitabine patients (p = 0.754. In the two groups, Grade 4 adverse events were not observed and Grade 3 consisted of only two cases of diarrhea, and no patient suffered hematologic adverse event of Grade 2 or higher. However, the incidence of diarrhea (62.5% vs 33.3%, p = 0.014 and hand-foot syndrome (29.2% vs 0%, p = 0.016 were higher in capecitabine group. Other adverse events did not differ significantly between two groups. CONCLUSIONS: The two preoperative chemoradiotherapy regimens were effective and safe for patients of locally advanced rectal cancer, but regimen with S-1 exhibited a lower incidence of adverse events.

  17. Guggulsterone of Commiphora mukul resin reverses drug resistance in imatinib-resistant leukemic cells by inhibiting cyclooxygenase-2 and P-glycoprotein.

    Science.gov (United States)

    Xu, Hong-Bin; Xu, Lu-Zhong; Mao, Xia-Ping; Fu, Jun

    2014-06-15

    The purpose of this study was to investigate the effects of guggulsterone on cyclooxygenase-2 and P-glycoprotein mediated drug resistance in imatinib-resistant K562 cells (K562/IMA). MTT cytotoxicity assay, flow cytometry, western blot analysis, and ELISA were performed to investigate the anti-proliferative effect, the reversal action of drug resistance, and the inhibitory effect on cyclooxygenase-2, P-glycoprotein, BCR/ABL kinase, and PGE2 release in K562/IMA cells by guggulsterone. The results showed that co-administration of guggulsterone resulted in a significant increase in chemo-sensitivity of K562/IMA cells to imatinib, compared with imatinib treatment alone. Rhodamine123 accumulation in K562/IMA cells was significantly enhanced after incubation with guggulsterone (60, 120 μM), compared with untreated K562/IMA cells (pP-glycoprotein and prostaglandin E2. However, guggulsterone had little inhibitory effect on the activity of BCR/ABL kinase. The present study indicates guggulsterone induces apoptosis by inhibiting cyclooxygenase-2 and down-regulating P-glycoprotein expression in K562/IMA cells.

  18. Preliminary comparison of efficacy and safety of dasatinib and imatinib in newly diagnosed chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    周励

    2013-01-01

    Objective To compare the efficacy and safety of dasatinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia(CML-CP).Methods37CML-CP patients were randomized to receive

  19. Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with collagen-induced arthritis (CIA).

    Science.gov (United States)

    Ando, Wataru; Hashimoto, Jun; Nampei, Akihide; Tsuboi, Hideki; Tateishi, Kosuke; Ono, Takeshi; Nakamura, Norimasa; Ochi, Takahiro; Yoshikawa, Hideki

    2006-01-01

    Macrophage colony-stimulating factor (M-CSF) is a key factor for osteoclastogenesis at the bone-pannus interface in patients with rheumatoid arthritis as well as a receptor activator of NF-kappaB ligand (RANKL). Imatinib mesylate inhibits the phosphorylation of c-fms, a receptor for M-CSF. The present study investigates the effect of imatinib mesylate on joint destruction in rats with collagen-induced arthritis (CIA) and on osteoclastogenesis in vitro. Imatinib mesylate (50 or 150 mg/kg), dexamethasone, or vehicle was administered daily to CIA rats for 4 weeks from the onset of arthritis. Hind-paw swelling and body weight were measured weekly. At weeks 2 and 4, the metatarsophalangeal (MTP) joints and the ankle and subtalar joints were radiographically and histologically assessed. The effect of imatinib mesylate on osteoclast formation from rat bone marrow cells with M-CSF and soluble RANKL (sRANKL) in vitro was also examined. Radiographic assessment showed that 150 mg/kg imatinib mesylate suppressed the destruction of the MTP and the ankle and subtalar joints at week 2, and MTP joint destruction at week 4 in CIA rats, although hind-paw swelling was not suppressed. The number of TRAP-positive cells at the bone-pannus interface was significantly reduced in the group administered with 150 mg/kg imatinib mesylate compared with that given vehicle at week 4. Imatinib mesylate dose-dependently inhibited the proliferation of M-CSF-dependent osteoclast precursor cells in vitro as well as osteoclast formation induced by M-CSF and sRANKL. These findings suggest that imatinib mesylate could prevent joint destruction in patients with rheumatoid arthritis.

  20. The effect of preoperative smoking cessation or preoperative pulmonary rehabilitation on outcomes after lung cancer surgery: a systematic review.

    Science.gov (United States)

    Schmidt-Hansen, Mia; Page, Richard; Hasler, Elise

    2013-03-01

    The preferred treatment for lung cancer is surgery if the disease is considered resectable and the patient is considered surgically fit. Preoperative smoking cessation and/or preoperative pulmonary rehabilitation might improve postoperative outcomes after lung cancer surgery. The objectives of this systematic review were to determine the effectiveness of (1) preoperative smoking cessation and (2) preoperative pulmonary rehabilitation on peri- and postoperative outcomes in patients who undergo resection for lung cancer. We searched MEDLINE, PreMedline, Embase, Cochrane Library, Cinahl, BNI, Psychinfo, Amed, Web of Science (SCI and SSCI), and Biomed Central. Original studies published in English investigating the effect of preoperative smoking cessation or preoperative pulmonary rehabilitation on operative and longer-term outcomes in ≥ 50 patients who received surgery with curative intent for lung cancer were included. Of the 7 included studies that examined the effect of preoperative smoking cessation (n = 6) and preoperative pulmonary rehabilitation (n = 1) on outcomes after lung cancer surgery, none were randomized controlled trials and only 1 was prospective. The studies used different smoking classifications, the baseline characteristics differed between the study groups in some of the studies, and most had small sample sizes. No formal data synthesis was therefore possible. The included studies were marked by methodological limitations. On the basis of the reported bodies of evidence, it is not possible to make any firm conclusions about the effect of preoperative smoking cessation or of preoperative pulmonary rehabilitation on operative outcomes in patients undergoing surgery for lung cancer.

  1. Imatinib-induced decompensated heart failure in an elderly patient with chronic myeloid leukemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Hai-Hong Ran; Ran Zhang; Xue-Chun Lu; Bo Yang; Hui Fan; Hong-Li Zhu

    2012-01-01

    Because it is safe and well tolerated, imatinib is a standard first-line therapy for chronic myeloid leukemia (CML). Although there have been sporadic reports of imatinib-induced cardiotoxicity, including left ventricle (LV) dysfunction and heart failure, the evidence for it is contradictory. Here, we reported a case of an 88-year-old male patient with CML developed decompensated heart failure following imatinib therapy. Four days after the initiation of imatinib, the patient developed orthopnea, edema and a pleural effusion accompanied by abdominal distension, nausea and vomiting. The chest X-ray film showed an enlarged cardiac profile. The echocardiogram demonstrated a decreased LV ejection fraction and enlarged left-side cardiac chambers. B-type natriuretic peptide concentrations were markedly increased. The patient recovered soon after the withdrawal of imatinib and introduction of comprehensive therapy for heart failure. Imatinib-induced cardiotoxicity in elderly patients is a potentially serious complication that merits further evaluation.

  2. Ulipristal acetate for pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands: cost minimization analysis and budget impact analysis.

    Science.gov (United States)

    Zakiyah, N; van Asselt, A D I; Postma, M J

    2017-03-01

    Ulipristal acetate has been found to be non-inferior to other pre-operative treatments of uterine fibroids, particularly leuprolide. The objective of this study was to assess the pharmacoeconomic profile of ulipristal acetate compared to leuprolide for the pre-operative treatment of moderate-to-severe uterine fibroids in women of reproductive age in The Netherlands. The analysis was performed and applied within the framework of the ulipristal acetate submission for reimbursement in 2012. A decision model was developed to compare the total costs of ulipristal acetate compared to leuprolide, the standard care in The Netherlands. The target population of this study corresponded to the type of patients included in the PEARL II clinical trial; i.e. women of reproductive age requiring pre-operative treatment for uterine fibroids. Sensitivity analysis was implemented to assess uncertainties. Data regarding costs, effects, and other input parameters were obtained from relevant published literatures, the Dutch Healthcare Insurance Board, and expert opinion obtained by means of a panel of experts from several medical centers in The Netherlands. In The Netherlands, the total costs of ulipristal acetate and leuprolide were estimated at €4,216,027 and €4,218,095, respectively. The annual savings of ulipristal acetate were, therefore, estimated at €2,068. The major driver of this cost difference was the cost of administration for leuprolide. Sensitivity analyses showed that ulipristal acetate mostly remained cost-saving over a range of assumptions. The budget impact analysis indicated that the introduction of ulipristal acetate was estimated to result in cost savings in the first 3 years following the introduction. The results of this study were used in the decision on reimbursement of ulipristal acetate according to the Dutch Reference Pricing system in 2012. Ulipristal acetate was cost saving compared to leuprolide and has the potential to provide substantial savings on

  3. Effects and Mechanism of Imatinib in Inhibiting Colon Cancer Cell Proliferation.

    Science.gov (United States)

    Samei, Lv; Yaling, Pang; Lihua, Yang; Yan, Zhang; Shuyan, Jiang

    2016-11-01

    BACKGROUND This study investigated the effects and mechanism of imatinib in inhibiting colon cancer cell proliferation. MATERIAL AND METHODS The SW480 cells were divided into 4 imatinib-treated groups: 0 μM, 1.25 μM, 2.5 μM, and 5μM. We analyzed the apoptosis and cell cycle of the 4 groups. The gene and protein expressions of p21, p27, HGF, and GAPDH were measured by RT-PCR and Western blot. RESULTS Compared with the 0-μM imatinib-treated group, the apoptosis of 1.25-μM, 2.5-μM, and 5.0-μM treated groups was significantly induced (P<0.05, all). The G1 phase was significantly up-regulated in the 1.25-μM, 2.5-μM, and 5.0-μM treated groups compared with the 0-μM imatinib-treated group (P<0.05, respectively), but the S and G2 phase of 3 imatinib-treated groups were significantly down-regulated (P<0.05, all). The gene and protein expressions of p27 and HGF were significantly different among the 4 groups (P<0.05, all). CONCLUSIONS Imatinib inhibits proliferation of colon cancer cells by reducing HGF and increasing p27 in a dose-dependent manner.

  4. Pre-operative anaemia.

    Science.gov (United States)

    Clevenger, B; Richards, T

    2015-01-01

    Pre-operative anaemia is a relatively common finding, affecting a third of patients undergoing elective surgery. Traditionally associated with chronic disease, management has historically focused on the use of blood transfusion as a solution for anaemia in the peri-operative period. Data from large series now suggest that anaemia is an independent risk associated with poor outcome in both cardiac and non-cardiac surgery. Furthermore, blood transfusion does not appear to ameliorate this risk, and in fact may increase the risk of postoperative complications and hospital length of stay. Consequently, there is a need to identify, diagnose and manage pre-operative anaemia to reduce surgical risk. Discoveries in the pathways of iron metabolism have found that chronic disease can cause a state of functional iron deficiency leading to anaemia. The key iron regulatory protein hepcidin, activated in response to inflammation, inhibits absorption of iron from the gastrointestinal tract and further reduces bioavailability of iron stores for red cell production. Consequently, although iron stores (predominantly ferritin) may be normal, the transport of iron either from the gastrointestinal tract or iron stores to the bone marrow is inhibited, leading to a state of 'functional' iron deficiency and subsequent anaemia. Since absorption from the gastrointestinal tract is blocked, increasing oral iron intake is ineffective, and studies are now looking at the role of intravenous iron to treat anaemia in the surgical setting. In this article, we review the incidence and impact of anaemia on the pre-operative patient. We explain how anaemia may be caused by functional iron deficiency, and how iron deficiency anaemia may be diagnosed and treated.

  5. Clinical study of suppository delivery of 5-fluorouracil and pathological effects on metastatic lymph nodes caused by preoperative combined treatment with radiation, intraluminal hyperthermia and 5-fluorouracil suppository in rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Takaaki [Kyoto Prefectural Univ. of Medicine (Japan)

    1997-11-01

    Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil (5-FU) suppository has been reported effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Suppository and intravenous 5-FU administration were compared with respect to tissue concentrations in rectal cancer cases. Just before the operation patients received 100 mg of 5-FU via suppository or intravenously. Portal and systemic blood, tumor tissue, normal mucosa and muscle layer separately at 5, 10, 15 cm in the oral direction from the tumor and the pararectal lymph node were harvested for high-performance liquid chromatography determination of 5-FU concentrations. Rectal 5-FU concentrations were significantly higher in the suppository cases compared with the intravenously administrated ones. Suppository distributed more 5-FU at pararectal lymph nodes than intravenous injection. This fact revealed 5-FU suppositories to be a useful drug delivery system for rectal cancer. The pathological effects on metastatic lymph nodes caused by combined treatment were evaluated in 22 cases. Normal lymph nodes showed congestion only. Fibrotic and necrotic changes were characteristic of damaged metastatic areas. In 6 cases (27.3%), no metastatic cells were detected on fibrotically changed areas. The down staging of the lymph node metastatic factor was carried out by preoperative combined treatment. High concentrations of 5-FU at mucosa could suggest the usefulness of 5-FU suppository administration just before operation for prevention of suture-line implantation. (author)

  6. Preoperative evaluation of oesophageal adenocarcinoma.

    Science.gov (United States)

    Khanna, Lauren G; Gress, Frank G

    2015-02-01

    The preoperative evaluation of oesophageal adenocarcinoma involves endoscopic ultrasound (EUS), computed tomography (CT), and positron emission tomography (PET). With routine Barrett's oesophagus surveillance, superficial cancers are often identified. EUS, CT and PET have a limited role in the staging of superficial tumours. Standard EUS has limited accuracy, but high frequency ultrasound miniprobes are valuable for assessing tumour stage in superficial tumours. However, the best method for determining depth of invasion, and thereby stage of disease, is endoscopic mucosal resection. In contrast, in advanced oesophageal cancers, a multi-modality approach is crucial. Accurate tumour staging is very important since the treatment of advanced cancers involves a combination of chemotherapy, radiation, and surgery. EUS is very useful for staging of the tumour and nodes. High frequency ultrasound miniprobes provide the ability to perform staging when the lesion is obstructing the oesophageal lumen. CT and PET provide valuable information regarding node and metastasis staging.

  7. The impact of ICU nurses' preoperative visit on treatment compliance of patients after lung transplantation%ICU护士术前访视对肺移植患者术后遵医行为的影响

    Institute of Scientific and Technical Information of China (English)

    王芳; 黄云娟; 许正红; 朱亭立; 黄琴红; 陈静瑜; 王俏英; 王玲秀

    2014-01-01

    Objective:To investigate the effects of preoperative visit on treatment compliance of patients after lung transplantation. Methods:Forty-two cases of lung transplant patients were enrolled and randomly divided into observation group and control group. And the observation group were interviewed before operation in ICU, the control group underwent routine preoperative preparation and education. Compliance was measured after operation. Results:Treatment compliance of observation group in the ifrst day and third day were 94.1%and 88.2%, and that in the control group was 88.0%and 84.0%, which showed a signiifcant difference between the two groups (P<0.05). Conclusion:ICU nurses' preoperative visits can effectively enhance the compliance of patients.%目的:探讨术前访视对肺移植患者术后遵医行为的影响。方法:将42例肺移植患者随机分为观察组和对照组,观察组接受ICU护士术前访视,对照组行常规术前准备及宣教,测评并比较患者术后遵医行为。结果:观察组术后第1天及第3天遵医率分别为94.1%、88.2%,对照组术后第1天及第3天遵医率分别为88.0%、84.0%,观察组遵医率高于对照组,差异有统计学意义(P<0.05)。结论:ICU护士术前访视能有效改善肺移植患者术后遵医行为。

  8. Imatinib Mesylate Effectiveness in Chronic Myeloid Leukemia with Additional Cytogenetic Abnormalities at Diagnosis among Black Africans

    Science.gov (United States)

    Aïssata, Tolo Diebkilé; Sawadogo, Duni; Nanho, Clotaire; Kouakou, Boidy; Meité, N'dogomo; Emeuraude, N'Dhatz; Roméo, Ayémou; Yassongui Mamadou, Sekongo; Kouéhion, Paul; Mozart, Konan; Koffi, Gustave; Sanogo, Ibrahima

    2013-01-01

    Imatinib mesylate provides good results in the treatment of CML in general. But what about the results of this treatment in CML associated with additional cytogenetic abnormalities at diagnosis among black Africans? For this, we retrospectively studied 27 cases of CML associated with additional cytogenetic abnormalities, diagnosed in the department of clinical hematology of the University Hospital of Yopougon in Côte d'Ivoire, from May 2005 to October 2011. The age of patients ranged from 13 to 68 years, with a mean age of 38 years and a sex ratio of 2. Patients were severely symptomatic with a high Sokal score of 67%. CML in chronic phase accounted for 67%. The prevalence of additional cytogenetic abnormalities was 29.7%. There were variants of the Philadelphia chromosome (18.5%), trisomy 8 (14.8%), complex cytogenetic abnormalities (18.5%), second Philadelphia chromosome (14.8%), and minor cytogenetic abnormalities (44.4%). Complete hematologic remission was achieved in 59%, with 52% of major cytogenetic remission. The outcome was fatal in 37% of patients. Death was related in 40% to hematologic toxicity and in 30% to acutisation. The median survival was 40 months. PMID:23802015

  9. Imatinib alters cell viability but not growth factors levels in TM4 Sertoli cells

    Science.gov (United States)

    Hashemnia, Seyyed Mohammad Reza; Atari-Hajipirloo, Somayeh; Roshan-Milani, Shiva; Valizadeh, Nasim; Mahabadi, Sonya; Kheradmand, Fatemeh

    2016-01-01

    Background: The anticancer agent imatinib (IM) is a small molecular analog of ATP that inhibits tyrosine kinase activity of platelet derived growth factors (PDGFs) and stem cell factor (SCF) receptor in cancer cells. However these factors have a key role in regulating growth and development of normal Sertoli, Leydig and germ cells. Objective: The aim of this study was to determine cell viability, PDGF and SCF levels in mouse normal Sertoli cells exposed to IM. Materials and Methods: In this experimental study, the mouse TM4 Sertoli cells were treated with 0, 2.5, 5, 10 and 20 μM IM for 2, 4 or 6 days. The cell viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, One-Way ANOVA was performed. Results: IM showed significant decrease in Sertoli cell viability compared to control group (p=0.001). However, IM increased PDGF and SCF level insignificantly (p>0.05). Conclusion: Results suggested that IM treatment induced a dose dependent reduction of cell viability in Sertoli cells. It seems that treatment with this anticancer drug is involved in the fertility process. Further studies are needed to evaluate the role of PDGF and SCF in this cell. PMID:27738659

  10. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Shuit-Mun Wong

    Full Text Available Chronic myeloid leukemia (CML is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

  11. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Science.gov (United States)

    Wong, Shuit-Mun; Liu, Fu-Hwa; Lee, Yueh-Lun; Huang, Huei-Mei

    2016-01-01

    Chronic myeloid leukemia (CML) is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

  12. Nose-to-brain transport of imatinib mesylate: A pharmacokinetic evaluation.

    Science.gov (United States)

    Hada, Nobuko; Netzer, William Joseph; Belhassan, Fanny; Wennogle, Lawrence Paul; Gizurarson, Sveinbjörn

    2017-02-24

    The delivery of drugs to the brain is a constant challenge due to limitations imposed by the blood-brain barrier (BBB). Various methods of bypassing the BBB are under investigation. One approach is intranasal administration, where the olfactory region of the nasal cavity extends up to the cranial cavity and provides direct access to the brain. The pharmacokinetics of this transport and factors that determine transport rates and capacity is of vital importance for evaluating the clinical value of this route. Here, the pharmacokinetics of intranasally administered imatinib has been explored. Imatinib is distributed into the brain following intravenous administration, and then rapidly removed. Following intravenous administration, the brain/plasma ratio for imatinib was calculated to be 2% and remained at this ratio for 30min. The brain/plasma ratio following intranasal administration, however, was found to be 5.3% and remained at this ratio for up to 90min. Imatinib was found to be rapidly transported into the brain via the olfactory region, by shutting down the nose-to-blood-to-brain transport with epinephrine. The increased brain concentration of imatinib (0.33μg/g tissue) achieved by intranasal administration, compared with an IV injection, is likely to provide a model for developing a wide range of CNS active molecules that were previously removed from consideration as drug candidates due to their lack of CNS access. Furthermore, brain imatinib levels were increased by co-administration of the p-gp substrates, elacridar and pantoprazole, showing that both compounds were able to inhibit the elimination of imatinib from the brain.

  13. Anterior mediastinal paraganglioma: A case for preoperative embolization

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    Shakir Murtaza

    2012-07-01

    Full Text Available Abstract Background Paraganglioma is a rare but highly vascular tumor of the anterior mediastinum. Surgical resection is a challenge owing to the close proximity to vital structures including the heart, trachea and great vessels. Preoperative embolization has been reported once to facilitate surgical treatment. Case presentation We report a case of anterior mediastinal paraganglioma that was embolized preoperatively, and was resected without the need for cardiopulmonary bypass and without major bleeding complications. Conclusion We make a case to further the role of preoperative embolization in the treatment of mediastinal paragangliomas.

  14. Is imatinib still the best choice as first-line oral TKI

    Directory of Open Access Journals (Sweden)

    Shweta Bansal

    2014-01-01

    Full Text Available Targeted therapy is the buzz word these days. A decade back the emergence of tyrosine kinase inhibitor Imatinib on the horizon, as the targeted therapy, had captured the imagination of everyone in the field of cancer. It is encouraging to see a large number of patients getting relief from deadly CML disease and leading a good quality of life with the help of this drug. However, sky is not the limit and now we have second and third generation tyrosine kinase inhibitors. I still remember the sagacious smile on the face of late Dr. John Goldman, when I asked him about his preferred choice and he replied and I quote "this is going to be the debate of the decade." Here I take the opportunity to contribute to this debate. I have scrutinized various aspects of the three TKIs, now recommended, for the treatment of CML. I`m still convinced it is too early to shift our practice completely towards 2G TKI as more time is required to make a clear recommendation.

  15. Imatinib enchances the sensitivity of gastrointestinal stromal tumors to topoisomerase II inhibitors

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    S. V. Boichuk

    2015-01-01

    Full Text Available Objective: to study the sensitivity of gastrointestinal stromal tumors (GISTs to the topoisomerases type II inhibitors and ability of imatinib to enhance GISTs sensitivity to the chemotherapeutic drugs indicated above.Subjects and Methods. We studied the sensitivity of gastrointestinal stromal tumors (GISTs to the topoisomerases II inhibitors and ability of imatinib to enhance GISTs sensitivity to these chemotherapeutic agents. The expression of DNA damage and repair (DDR markers was examined by western-blotting. Cleaved forms of poly (ADP-rybose polymerase and caspase-3 were served as an apoptotic markers measured by western blotting. Amount of apoptotic cells was counted by flow cytometry analysis by using a propidium iodide DNA staining procedure and counting the numbers of hypodiploid cells.Results. We observed the sensitivity of GISTs to topoisomerase II inhibitors – doxorubicine and etoposide inducing DNA double-strand breaks and apoptotic cell death. Imatinib enhances GISTs sensitivity to topoisomerase II inhibitors. This might be due to reduced ability of GISTs to repair DNA damage by homologous recombination. Imatinib-induced reduction of Rad51 recombinase might be due to increased proteasome-dependent degradation.Conclusion. GIST cells are sensitive to topoisomerase II inhibitors (etoposide and doxorubicin in vitro. Imatinib enhances GISTs sensitivity to the chemotherapeutic agents indicated above.

  16. Adherence to imatinib therapy in gastrointestinal stromal tumors and chronic myeloid leukemia.

    Science.gov (United States)

    Al-Barrak, Jasem; Cheung, Winson Y

    2013-08-01

    The number of anticancer drugs available in oral formulation has risen sharply in the past few years and this is expected to continue to increase over the next several decades. For patients, the convenience of self-administration constitutes a major benefit associated with oral therapy. For clinicians, however, the transition from parenteral to oral therapy has resulted in concerns about adherence to therapy, its monitoring, and its effects on clinical outcomes. Several studies have demonstrated that imatinib is effective at improving overall survival and/or recurrence-free survival in patients with gastrointestinal stromal tumors and chronic myeloid leukemia (primary and metastatic disease). Despite the survival benefit and the favorable toxicity profile of imatinib, however, adherence to imatinib remains poor. Herein, we review the evidence showing the effects of nonadherence on patient outcomes as well as data indicating that adherence to imatinib (and oral anticancer therapy in general) is suboptimal. We also highlight factors that may contribute to nonadherence and suggest key steps that can be implemented by the multidisciplinary medical team to overcome the daily challenges of adherence. Improving adherence to imatinib depends on open communication and comprehensive patient education. All of this is essential to maximize benefits from therapy and improve clinical outcomes for our patients.

  17. Preoperative anxiety in neurosurgical patients.

    Science.gov (United States)

    Perks, Anna; Chakravarti, Sucharita; Manninen, Pirjo

    2009-04-01

    Anxiety is common in surgical patients, with an incidence of 60% to 92%. There is little information on the incidence and severity of preoperative anxiety in patients scheduled for neurosurgery. The aim of this study was to measure the level of preoperative anxiety in neurosurgical patients and to assess any influencing factors. After the Institutional Review Board approval and informed written consent, 100 patients booked for neurosurgery were interviewed preoperatively. Each patient was asked to grade their preoperative anxiety level on a verbal analog scale, Amsterdam Preoperative Anxiety and Information Scale, and a set of specific anxiety-related questions. The anxiety scores and the responses to the questions were compared between the sex, age, weight, diagnosis, and history of previous surgery. The mean age (+/-SD) was 50+/-13 years. The preoperative diagnosis was tumor (n=64), aneurysm (n=14), and other (n=22). Overall verbal analog scale was 5.2+/-2.7; the score was higher for female (5.8+/-2.8) than male patients (4.6+/-2.5) (PAmsterdam Preoperative Anxiety and Information Scale anxiety and knowledge scores were greater for surgery than for anesthesia. Questionnaire results showed that the most common anxieties were waiting for surgery, physical/mental harm, and results of the operation. In conclusion, our study showed that neurosurgical patients have high levels of anxiety, with a higher incidence in females. There was a moderately high need for information, particularly in patients with a high level of preoperative anxiety.

  18. Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate: A case report

    Institute of Scientific and Technical Information of China (English)

    D Tzilves; A Gatopoulou; K Zervas; E Katodritou; F Patakiouta; A Tarpagos; I Katsos

    2007-01-01

    Gastrointestinal stromal tumors (GISTs) are rare tumors,which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, coexistance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection.Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered.During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma.To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST.

  19. Nonaqueous capillary electrophoresis of imatinib mesylate and related substances.

    Science.gov (United States)

    Ye, Lei; Huang, Yifei; Li, Jian; Xiang, Guangya; Xu, Li

    2012-08-01

    In the present study, nonaqueous capillary electrophoretic separation of imatinib mesylate (IM) and related substances, N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine (PYA), N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)-4-((piperazin-1-yl)methyl) benzamide (NDI) and 4-chloromethyl-N-(4-methyl-3-((4-(pyridin-3-yl) pyrimidin-2-yl) amino) phenyl) benzamide (CPB) was developed. The influential factors affecting separation, including type and concentration of the electrolyte, applied voltage, and buffer modifier were investigated. Baseline separation of the studied analytes was obtained using a buffer of 50 mM Tris and 50 mM methanesulfonic acid in methanol at a apparent pH (pH*) of 1.65. To enhance the sensitivity, large-volume sample stacking was employed for online concentration. The strongest analytical signal with a suitable separation was achieved when the injection time was 100 s. The linearity ranges of PYA and NDI were 0.100-2.50 μg mL(-1), and that of CPB was 0.125-2.50 μg mL(-1), with good coefficients (r(2) > 0.9948). The relative standard deviations of intra- and interday were satisfactory. Under the optimized conditions, seven batches of the synthesized samples were analyzed and CPB was detected in two batches. Owing to its simplicity, effectiveness, and low price, the developed method is promising for quality control of IM.

  20. Generalized lichenoid drug eruption associated with imatinib mesylate therapy

    Directory of Open Access Journals (Sweden)

    Sudip Kumar Ghosh

    2013-01-01

    Full Text Available Imatinib mesylate (IM, an anticancer drug, has been widely used to treat chronic myeloid leukemia (CML, gastrointestinal stromal tumors (GIST, and dermato-fibrosarcoma protuberans. Cutaneous reactions to IM have been reported to occur in varying number of patients in different case series. Non-lichenoid cutaneous reactions secondary to IM have been well-documented in the literature and are the commonest non-hematologic adverse reactions associated with its use. Lichenoid drug eruption (LDE associated with IM therapy has rarely been reported in the literature. A case of a generalized LDE associated with IM therapy has been described here for its rarity and interesting clinical presentation. As the clinical usage of IM is increasing, one might expect an increasing number of similar patients in the future. It is thus important to realize the potential of IM to produce LDE and to differentiate this entity from idiopathic lichen planus. In the present article, the reports of IM-associated LDE, described in the PubMed and Medline database (in English language literature, have also been reviewed.

  1. Generalized lichenoid drug eruption associated with imatinib mesylate therapy.

    Science.gov (United States)

    Ghosh, Sudip Kumar

    2013-09-01

    Imatinib mesylate (IM), an anticancer drug, has been widely used to treat chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GIST), and dermato-fibrosarcoma protuberans. Cutaneous reactions to IM have been reported to occur in varying number of patients in different case series. Non-lichenoid cutaneous reactions secondary to IM have been well-documented in the literature and are the commonest non-hematologic adverse reactions associated with its use. Lichenoid drug eruption (LDE) associated with IM therapy has rarely been reported in the literature. A case of a generalized LDE associated with IM therapy has been described here for its rarity and interesting clinical presentation. As the clinical usage of IM is increasing, one might expect an increasing number of similar patients in the future. It is thus important to realize the potential of IM to produce LDE and to differentiate this entity from idiopathic lichen planus. In the present article, the reports of IM-associated LDE, described in the PubMed and Medline database (in English language literature), have also been reviewed.

  2. Potential relevance of pre-operative quality of life questionnaires to identify candidates for surgical treatment of genital prolapse: a pilot study

    Directory of Open Access Journals (Sweden)

    Chauvin Christian

    2012-03-01

    Full Text Available Abstract Background To evaluate prolapse-related symptoms, quality of life and sexuality of patients with validated questionnaires before and after surgery for genital prolapse and assess relevance of such an evaluation to select women for surgery. Methods From November 2009 to April 2010, 16 patients operated on for genital prolapse of grade greater than or equal to 2 (POP-Q classification were evaluated prospectively by three questionnaires of quality of life Pelvic Floor Distress Inventory (PFDI-20, Pelvic Floor Impact Questionnaire (PFIQ-7 and Pelvic Organ Prolaps/Urinary Incontinence Sexual Questionnaire (PISQ-12. Data were collected the day before surgery and 6 weeks postoperatively. Results Eleven patients had laparoscopic surgery and five vaginal surgery. There was a significant decrease in pelvic heaviness, vaginal discomfort and urinary symptoms after surgery. The score of symptoms of prolapse, the PFDI-20 score was 98.5 preoperatively and 31.8 postoperatively (p Conclusions This study suggests that surgery improves quality of life of patients with genital prolapse. Quality of life questionnaires could help select good candidates for surgery. Further studies are required to determine threshold to standardize indications of surgery.

  3. Role of a preoperative distal and proximal embolization of the right branch of the portal vein at surgical treatment of a liver malignant tumors

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    Popov M.V.

    2016-12-01

    Full Text Available Objective: assessment of safety and efficiency of application of the method of the distal and proximal embolization of the right branch of a portal vein using an occluder for preventive increase of the small future remaining liver amount in case of the planned resection. Material and methods. In the Burnazyan Federal Medical Biophysical Center that method was used in two cases: metastasises of bladder cancer in one case and of colorectal cancer in second case. Patients were males aged 57 and 64. Measuring the amount of future remaining liver volume was carried out with the CT-volumetry. Portal vein embolization of the right branch was carried out by transhepatic ipsilateral access using polyvinyl alcohol particles and occluder AVP II. Results. As a result in both cases the gain (9 and 24%, sufficient for performance of a resection, of the remaining liver volume was noted; the progression of the tumor process and periop-erative complications were not observed. Conclusion. Distal and proximal preoperative portal vein embolization is an effective and promising method, allowing surgeons to increase the number of operable patients and reduce the risk of postoperative liver failure.

  4. 肢端肥大症术前使用生长抑素类似物的经济学评价研究%Pharmacoeconomic Evaluation on the Preoperative Treatment of Acromegaly with Somatostatin Analogues in Shanghai

    Institute of Scientific and Technical Information of China (English)

    何江江; 李益明; 庄妍; 吴蔚; 刘晓霞; 金佳; 郑红淑; 朱国兰; 胡善联

    2014-01-01

    通过回顾性临床研究,开展生长抑素类似物(兰瑞肽和奥曲肽)在上海地区用于肢端肥大症术前治疗的药物经济学评价。收集到上海某三甲医院2009年1月1日-2013年6月30日的89例肢端肥大症患者的病史档案资料。研究结果显示,兰瑞肽和奥曲肽用于中国人群的临床疗效(IGF-I水平)控制达标情况相当,且与纯手术组不存在统计学差异;药品干预组的治疗费用明显高于纯手术组,但在干预组中,兰瑞肽组相对于奥曲肽组具有一定的成本优势。%This study evaluated the pharmacoeconomic effect of preoperative treatment of acromegaly in Shanghai by using Octreotide and Lanreotide through retrospective clinical study. The medical records of 89 acromegaly patients in a sampling hospital were collected during January 1, 2009 to June 30, 2013. Both Lanreotide and Octreotide were proven to be effective and fairly equivalence in lowering the level of IGF-I in the preoperative treatment of Chinese patients with acromegaly, and there was no signiifcant difference from the sole surgery group. The costs of treatment per patient of the sole surgery group was obviously lower than those of the drug intervention groups, however, the Lanreotide group had a cost-effective advantage over the Octreotide group.

  5. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide.

    Science.gov (United States)

    Dresemann, Gregor; Weller, Michael; Rosenthal, Mark A; Wedding, Ulrich; Wagner, Wolfgang; Engel, Erik; Heinrich, Bernhard; Mayer-Steinacker, Regine; Karup-Hansen, Anders; Fluge, Oystein; Nowak, Anna; Mehdorn, Maximilian; Schleyer, Eberhard; Krex, Dietmar; Olver, Ian N; Steinbach, Joachim P; Hosius, Christian; Sieder, Christian; Sorenson, Greg; Parker, Richard; Nikolova, Zariana

    2010-02-01

    A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0-2 who had completed previous treatment comprising surgical resection, irradiation therapy, and first-line chemotherapy (preferably temozolomide (TMZ) containing regimen) and who have progressed despite treatment. If first-line chemotherapy did not contain TMZ, a second completed chemotherapy was acceptable. The primary efficacy parameter was progression-free survival (PFS). The primary comparison of combination therapy versus monotherapy for PFS was not significant (adjusted P = 0.56). The hazard ratio (HR) (adjusted HR = 0.93) was not clinically relevant. The median PFS for the combination arm was low at 6 weeks and similar to the median PFS in the monotherapy arm (6 weeks). The 6-month PFS for the two treatment groups was very similar (5% in the combination arm vs. 7% in the monotherapy arm). No clinically meaningful differences were found between the two treatment arms, and the primary study end point was not met. Among the patients receiving imatinib, no adverse events were reported that were either previously unknown or unexpected as a consequence of the disease.

  6. Marrow signal changes observed in follow-up whole-body MRI studies in children and young adults with neurofibromatosis type 1 treated with imatinib mesylate (Gleevec) for plexiform neurofibromas

    Energy Technology Data Exchange (ETDEWEB)

    Karmazyn, Boaz; Cohen, Mervyn D. [Riley Hospital for Children, Indiana University Health, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN (United States); Jennings, Samuel Gregory [Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Robertson, Kent A. [Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN (United States)

    2012-10-15

    We observed bone marrow signal changes (BMSC) in patients with plexiform neurofibromas after treatment with imatinib mesylate (Gleevec). To evaluate the pattern and natural history of BMSC. The data were obtained from a pilot study of imatinib mesylate in patients with plexiform neurofibromas. All patients underwent baseline and sequential whole-body STIR 1.5-T MRI after treatment. The bone marrow signal on MRI was evaluated for abnormalities, location and pattern, and any change on follow-up studies. The study group included 16 patients (8 males) with a median age of 14 years (range 4 to 25 years). The mean whole-body MRI follow-up duration was 1.9 years. Of the 16 patients, 14 (88%) developed BMSC. The signal change was asymmetrical in 9 of the 14 patients (64%). The appendicular skeleton was involved in all 14 patients and the axial skeleton in 3 patients (21%). BMSC was followed in 13 patients and decreased signal was seen in 9 patients (69%) after a mean duration of 1.3 years of treatment (range 0.6 to 2.9 years); no complications were observed. BMSC appeared in most patients with neurofibromatosis type 1 following treatment with imatinib mesylate. BMSC was unusually asymmetrical and involved the lower extremities. On follow-up, BMSC often showed a decrease without complications. (orig.)

  7. Analysis of imatinib in bone marrow and plasma samples of chronic myeloid leukaemia patients using solid phase extraction LC-ESI-MS

    OpenAIRE

    Iqbal, Z; Elliott, M; Watson, D.G.; Holyoake, T. L.; Jorgensen, H G

    2011-01-01

    The LC-ESI-MS was developed and validated for the analysis of imatinib in plasma and bone marrow samples using deuterated imatinib (D(8)-IM) as an internal standard. The biological samples were extracted using Strata-X-C SPE cartridges and separated on C8 column (50 x 3 mm, 3 µm), and methanol: 0.1% formic acid (70:30) was delivered at the rate of 0.7 ml/min as a mobile phase. Imatinib was quantified in samples by monitoring the ions m/z 494.3 for imatinib and 502.3 for D8-imatinib on ma...

  8. Imatinib mesylate inhibits proliferation and exerts an antifibrotic effect in human breast stroma fibroblasts.

    Science.gov (United States)

    Gioni, Vassiliki; Karampinas, Theodoros; Voutsinas, Gerassimos; Roussidis, Andreas E; Papadopoulos, Savvas; Karamanos, Nikos K; Kletsas, Dimitris

    2008-05-01

    Tumor stroma plays an important role in cancer development. In a variety of tumors, such as breast carcinomas, a desmoplastic response, characterized by stromal fibroblast and collagen accumulation, is observed having synergistic effects on tumor progression. However, the effect of known anticancer drugs on stromal cells has not been thoroughly investigated. Imatinib mesylate is a selective inhibitor of several protein tyrosine kinases, including the receptor of platelet-derived growth factor, an important mediator of desmoplasia. Recently, we have shown that imatinib inhibits the growth and invasiveness of human epithelial breast cancer cells. Here, we studied the effect of imatinib on the proliferation and collagen accumulation in breast stromal fibroblasts. We have shown that it blocks the activation of the extracellular signal-regulated kinase and Akt signaling pathways and up-regulates cyclin-dependent kinase inhibitor p21(WAF1), leading to the inhibition of fibroblast proliferation, by arresting them at the G(0)/G(1) phase of the cell cycle. Imatinib inhibits more potently the platelet-derived growth factor-mediated stimulation of breast fibroblast proliferation. By using specific inhibitors, we have found that this is due to the inhibition of the Akt pathway. In addition, imatinib inhibits fibroblast-mediated collagen accumulation. Conventional and quantitative PCR analysis, as well as gelatin zymography, indicates that this is due to the down-regulation of mRNA synthesis of collagen I and collagen III-the main collagen types in breast stroma-and not to the up-regulation or activation of collagenases matrix metalloproteinase 2 and matrix metalloproteinase 9. These data indicate that imatinib has an antifibrotic effect on human breast stromal fibroblasts that may inhibit desmoplastic reaction and thus tumor progression.

  9. Monitoração molecular da Leucemia Mielóide Crônica na era do imatinibe Molecular monitoring of Chronic Myeloid Leukemia in the imatinib era

    Directory of Open Access Journals (Sweden)

    Israel Bendit

    2008-04-01

    Full Text Available Nos últimos dez anos, o tratamento da leucemia mielóide crônica (LMC passou por uma grande mudança com a introdução da terapia alvo, onde o mesilato de imatinibe (MI atua inibindo a atividade tirosina quinase do transcrito BCR-ABL produto este do cromossomo Filadélfia (Ph. Esta revolução terapêutica obrigou que técnicas moleculares, até então de uso restrito na oncohematologia, como a reação em cadeia da polimerase em tempo real (RQ-PCR, fossem necessárias para monitorar o sucesso terapêutico ou a detecção precoce da perda de resposta ao MI. Nesta revisão estão delineados, de forma resumida, os principais procedimentos quanto à monitoração dos pacientes com LMC em tratamento com o MI segundo o Consenso Brasileiro de LMC.Treatment of chronic myeloid leukemia (CML has changed since the introduction of imatinib mesylate (IM 10 years ago. IM acts as a target therapy against the BCR-ABL gene by inhibiting its tyrosine kinase activity. This revolution in treating CML compels the introduction of molecular techniques, such as real time quantitative polymerase chain reaction (RQ-PCR to monitor the response to IM by providing an accurate measurement of the degree to which the BCR-ABL transcript is reduced or an early detection of loss of response identified by a rising level of BCR-ABL. In this review, we summarize the Brazilian CML consensus regarding the main procedures used to monitor CML patients treated with IM.

  10. Does the addition of oxaliplatin to preoperative chemoradiation benefit cT4 or fixed cT3 rectal cancer treatment? A subgroup analysis from a prospective study.

    Science.gov (United States)

    Wiśniowska, K; Nasierowska-Guttmejer, A; Polkowski, W; Michalski, W; Wyrwicz, L; Pietrzak, L; Rutkowski, A; Malinowska, M; Kryński, J; Kosakowska, E; Zwoliński, J; Winiarek, M; Olędzki, J; Kuśnierz, J; Zając, L; Bednarczyk, M; Szczepkowski, M; Tarnowski, W; Paśnik, K; Radziszewski, J; Partycki, M; Bęczkowska, K; Styliński, R; Wierzbicki, R; Bury, P; Jankiewicz, M; Paprota, K; Lewicka, M; Ciseł, B; Skórzewska, M; Mielko, J; Danek, A; Nawrocki, G; Sopyło, R; Kępka, L; Bujko, K

    2016-12-01

    Whether there is any benefit derived from adding oxaliplatin to fluoropyrimidine-based preoperative chemoradiation is currently unknown in cases of advanced cT3 or cT4 tumours. Our aim was to evaluate this issue by analysing a randomized trial, which compared two schedules of preoperative treatment (chemoradiation vs. 5 × 5 Gy with 3 cycles of consolidation chemotherapy) for cT4 or fixed cT3 rectal cancer. Delivery of oxaliplatin was mandatory to the first part of the study. For the second part, its delivery in both treatment-assigned groups was left to the discretion of the local investigator. We analysed a subgroup of 272 patients (136 in the oxaliplatin group and 136 in the fluorouracil-only group) from institutions that had omitted oxaliplatin in the second part of the study. Circumferential resection margin negative (CRM-) status rate was 68% in the oxaliplatin group and 70% in the fluorouracil-only group, p = 0.72. The pathological complete response rate (pCR) was correspondingly 14% vs. 7%, p = 0.10. Following multivariable analysis, when comparing the CRM- status in the oxaliplatin group to the fluorouracil-only group, the odds ratio was 0.79 (95 CI 0.35-1.74), p = 0.54; there being no interaction between concomitant chemoradiation and 5 × 5 Gy with consolidation chemotherapy; pinteraction = 0.073. For pCR, the corresponding results were 0.47 (95 CI 0.19-1.16), p = 0.10, pinteraction = 0.84. No benefit was found of adding oxaliplatin in terms of CRM nor pCR rates for either concomitant or sequential settings in preoperative radiochemotherapy for very advanced rectal cancer. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  11. Effect of Imatinib on the Oogenesis and Pituitary -Ovary Hormonal Axis in Female Wistar Rat

    OpenAIRE

    Parichehreh Yaghmaei; Kazem Parivar; Fatemeh Jalalvand

    2009-01-01

    Background: Imatinib mesylate, a small-molecular analog of adenosine triphosphate (ATP)that potently inhibits tyrosine kinase activities of Bcr–Abl, PDGFR-β, PDGFR-α, c-Fms, Argand c-kit, is one of the novel molecularly targeted drugs being introduced into cancer therapy.We tested the effect of imatinib on the ovarian histological structure and the concentration ofestrogen and progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH)in the serum of female Wistar rats.Mater...

  12. Preoperative alcoholism and postoperative morbidity

    DEFF Research Database (Denmark)

    Tonnesen, H; Kehlet, H

    1999-01-01

    BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

  13. 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.

  14. Efeitos adversos e resposta citogenética em pacientes com leucemia mieloide crônica tratados com imatinibe Adverse events and cytogenetc response in patients with chronic myeloid leukemia treated with imatinib

    Directory of Open Access Journals (Sweden)

    Tatiana F. Alvarenga

    2010-01-01

    pacientes.Chronic myeloid leukemia (CML is a clonal myeloproliferative disorder characterized cytogenetically by the Philadelphia chromosome (Ph. Therapeutic options of this disease are: hydroxyurea, interferon-a, allogeneic HSCT and more recently imatinib. This latter therapy demonstrated efficacy in the treatment of CML, particularly in the chronic phase. However some studies have demonstrated that there are additional chromosomal alterations related to resistance while others have reported undesirable clinical manifestations during imatinib therapy such as headache, nausea and vomiting. Because of the importance of this new molecular target therapy, it may be necessary to analyze the response of this treatment in respect to the quality of life of patients. The aim of this study was to analyze the clinical manifestations and the cytogenetic response during imatinib therapy in fifty-one patients with CML who had previously been treated using interferon-a. Cytogenetic analysis was performed in bone marrow cells using GTG-banding. The commonest clinical manifestations were mild to moderate: headache (37%, nausea (37%, vomiting (33% and edema (33%. Patients that achieved major cytogenetic response had a significantly longer median survival than patients without response (p=0.007. Eight patients evolved to death; none of them exhibited cytogenetic responses to imatinib. Our results show the importance of the clinical (analyzing the degree of tolerance to the drug and cytogenetic follow-up, where the presence of additional chromosomal alterations showed a distinct biological pattern that is not identifiable by molecular techniques, and so cytogenetic analysis is an important tool for the diagnosis and monitoring of this group of patientss.

  15. Preoperatively diagnosed mucocele of the appendix.

    Science.gov (United States)

    Rojnoveanu, Gh; Ghidirim, Gh; Mishin, I; Vozian, M; Mishina, A

    2014-01-01

    Mucocele of the appendix is an infrequent entity, characterized by distension of the lumen due to accumulation of mucoid substance and is rarely diagnosed preoperatively. If untreated, mucocele may rupture producing a potentially fatal entity known as pseudomyxoma peritonei. The type of surgical treatment is related to the dimensions and the histology of the mucocele. Appendectomy is used for simple mucocele or for cystadenoma. Right hemi-colectomy is recommended for cystadeno carcinoma. In this paper, we report a case of an asymptomatic 37-year-old woman in whom mucocele was found on a routine ultrasound examination and preoperative computed tomography scan. Surgery revealed a big appendix measuring 84 mm in length and 40 mm in diameter. The final pathologic diagnosis was simple mucocele. Celsius.

  16. Tuberculous and Non-Tuberculous Granulomatous Lymphadenitis in Patients Receiving ImatinibMesylate (Glivec for Metastatic Gastrointestinal Stromal Tumor

    Directory of Open Access Journals (Sweden)

    Abbas Agaimy

    2013-03-01

    Full Text Available Background: Imatinib mesylate (IM is the standard treatment for BCR-ABL-positive chronic myelogenous leukemia (CML and is the first-line adjuvant and palliative treatment for metastatic and inoperable gastrointestinal stromal tumor (GIST. IM is not known to be associated with an increased risk for development of granulomatous diseases. Methods: We describe our experience with 2 patients (42 and 62 years of age who developed granulomatous disease during IM treatment for metastatic GIST. Results: Mean duration of IM treatment was 12 (range 8-16 months. Enlarged lymph nodes with increased metabolism on FDG-PET-CT examination were detected and resected. Affected sites were supraclavicular (1 and subcarinal/mediastinal (1 lymph nodes. Histological examination revealed caseating and non-caseating granulomas suggestive of tuberculosis and sarcoidosis, respectively. Mycobacterium tuberculosis was detected by PCR in lymph nodes of 1 patient who was then successfully treated by anti-tuberculous agents. The other patient had negative sputum test for acid-fast bacilli and PCR-DNA-analysis was negative for M. tuberculosis and other mycobacteria. He received no anti-tuberculous therapy and had no evidence of progressive lymphadenopathy or new lung lesions during follow-up. Conclusion: Our observations underline the necessity to obtain biopsy material from enlarged or metabolically active lymph nodes developing during IM treatment for timely diagnosis and appropriate treatment of these rare complications. Follow-up without treatment is safe for patients without detectable microorganisms by sputum examination and PCR.

  17. Phase I trial of cisplatin, pemetrexed, and imatinib mesylate in chemo-naïve patients with unresectable malignant pleural mesothelioma

    Science.gov (United States)

    Tsao, AS; Harun, N; Lee, J.J; Heymach, J; Pisters, K; Hong, WK; Fujimoto, J; Wistuba, I

    2016-01-01

    Background We conducted a phase I trial of cisplatin-pemetrexed-imatinib mesylate, an oral PDGFR inhibitor, in chemo-naive MPM patients. Methods A standard 3+3 dose-escalating trial was used with the endpoints of MTD, response rate, survival, safety/toxicity and tumor PDGFR levels. Results 17 MPM patients were enrolled. The most common (any grade) side effects were nausea, fatigue, hypomagnesemia, and anemia. The MTD was established at dose level 3 (imatinib 600 mg) with the DLT nausea and vomiting. The median PFS was 7.9 months and median OS was 8.8 months. Sarcomatoid patients have worse PFS (p=0.01) and OS (p=0.009), while better ECOG PS 0–1 predicted for improved OS (p=0.001) and PFS (p=0.013). The 6 patients who completed all 6 treatment cycles had better OS (p=0.006), their median PFS was 9.6 months and OS was 22.4 months. In the translational studies, 14 patients had adequate tumor tissue that could be assessed for IHC and FISH. Patients with higher than median p- PDGFRα IHC expression had a better OS (p=0.013). When assessed as a continuous variable, higher p-PDGFRα in tumor cells correlated with an improved OS (p=0.045). None of the other 8 IHC biomarkers were predictive or prognostic for survival. Twelve patients had successful PDGFRB FISH results, but none met the criteria of ≥ 4 copies of PDGFRB gene, thus a correlation with clinical outcomes could not be done. Conclusions Cisplatin-pemetrexed-imatinib mesylate has clinical benefit in some MPM patients but was not well-tolerated. Further investigation into alternative anti-angiogenic agents, including PDGFRα inhibitors is warranted. PMID:24492162

  18. Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase.

    Science.gov (United States)

    Guérin, Annie; Chen, Lei; Ionescu-Ittu, Raluca; Marynchenko, Maryna; Nitulescu, Roy; Hiscock, Robert; Keir, Christopher; Wu, Eric Qiong

    2014-11-01

    Chronic myeloid leukemia (CML) treatment relies on tyrosine kinase inhibitors (TKIs), but their use can be associated with low-grade adverse events (AEs). This analysis aimed to identify the low-grade AEs which significantly impact the Health Related Quality of Life (HRQoL) of CML patients in chronic phase (CP) and to compare the incidence of such AEs among nilotinib- and imatinib-treated patients. Data from the 48 month ENESTnd trial were used (N = 593 patients). HRQoL was assessed using generic (SF-36) and leukemia-specific (FACT-Leu) HRQoL surveys. AEs were categorized into 26 system organ classes. In the adjusted regression model, five low-grade AE categories - gastrointestinal disorders, blood and lymphatic system disorders, general disorders and administration site conditions, musculoskeletal disorders, and psychiatric disorders - significantly impaired at least one HRQoL score. The incidence rate of these five AE categories was either significantly lower for nilotinib than imatinib or not different between the two drugs. The AE categories with lower incidence for both nilotinib 300 mg BID and 400 mg BID versus imatinib 400 mg daily were gastrointestinal, blood and lymphatic system, and musculoskeletal; nilotinib 300 mg BID had lower incidence than imatinib for general disorders. Low-grade AEs were grouped and analyzed by system organ class category, so the effect of some rare individual AEs on HRQoL may have been missed. The impact of low-grade AEs on HRQoL should be taken into account, along with other factors, when selecting the optimal treatment for patients newly diagnosed with CML-CP.

  19. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.

    Science.gov (United States)

    Kantarjian, Hagop; Giles, Francis; Wunderle, Lydia; Bhalla, Kapil; O'Brien, Susan; Wassmann, Barbara; Tanaka, Chiaki; Manley, Paul; Rae, Patricia; Mietlowski, William; Bochinski, Kathy; Hochhaus, Andreas; Griffin, James D; Hoelzer, Dieter; Albitar, Maher; Dugan, Margaret; Cortes, Jorge; Alland, Leila; Ottmann, Oliver G

    2006-06-15

    Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50. In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily. Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission. Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML. (ClinicalTrials.gov number, NCT00109707 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.

  20. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

    NARCIS (Netherlands)

    D.A. Reardon; G. Dresemann; S. Taillibert; M. Campone (Mario); M.J. van den Bent (Martin); P.M.J. Clement (Paul); E. Blomquist; L. Gordower; H. Schultz; J. Raizer; P. Hau (Peter); J. Easaw; M. Gil (Miguel); J. Tonn; A. Gijtenbeek; U. Schlegel; P. Bergström (Per); S. Green; A.E. Weir (Angela); Z. Nikolova

    2009-01-01

    textabstractBackground: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutio

  1. Patients Taking Imatinib for CML Have Similar Risk of Death as General Population

    Science.gov (United States)

    In an international study, the risk of death for chronic myelogenous leukemia patients treated with imatinib (Gleevec) who had been in remission for at least 2 years was not different from that of the general population, according to an article in the March 21, 2011 issue of the Journal of the National Cancer Institute.

  2. Philadelphia chromosome-positive mixed phenotype acute leukemia in the imatinib era.

    Science.gov (United States)

    Shimizu, Hiroaki; Yokohama, Akihiko; Hatsumi, Nahoko; Takada, Satoru; Handa, Hiroshi; Sakura, Toru; Nojima, Yoshihisa

    2014-10-01

    Although the introduction of imatinib dramatically improved the outcomes for patients with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph + BCP-ALL), the survival benefit of imatinib has not been assessed in the context of Ph + mixed phenotype acute leukemia (Ph + MPAL). To clarify this important issue, we studied 42 Ph+ acute leukemia (Ph + AL) patients who received intensive chemotherapy and concurrent administration of imatinib. Of the 42 Ph + AL patients, 13 (31%) patients were categorized as Ph + MPAL (positive for both myeloid and B-cell lineage), 27 (64%) were categorized as Ph + BCP-ALL, and two (5%) were categorized as Ph + acute myeloid leukemia. The complete remission rates after the initial induction therapy were not significantly different when comparing Ph + MPAL and Ph + BCP-ALL patients (100% vs. 85%, respectively, P = 0.14). Likewise, there were no significant differences in the 5-yr overall survival (OS) or disease-free survival (DFS) rates when comparing the MPAL and BCP-ALL groups (OS: 55% vs. 53%, respectively, P = 0.87, DFS: 46% vs. 42%, respectively, P = 0.94). These findings suggest that concurrent imatinib administration with chemotherapy improved the outcomes of Ph + MPAL patients to the level seen in Ph+BCP-ALL patients and should, therefore, be considered as the standard therapy for these patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Bioequivalence study of 400 and 100 mg imatinib film-coated tablets in healthy volunteers.

    Science.gov (United States)

    Ostrowicz, Andrzej; Mikołajczak, Przemysław L; Wierzbicka, Marzena; Boguradzki, Piotr

    2014-01-01

    The aim of the study was to investigate the bioavailability of a generic product of 100 mg and 400 mg imatinib film-coated tablets (test) as compared to that of a branded product (reference) at the same strength to determine bioequivalence. The secondary objective of the study was to evaluate tolerability of both products. An open-label, randomized, crossover, two-period, single-dose, comparative study was conducted in 43 (Imatynib-Biofarm 100 mg film-coated tablet) and in 42 (Imatynib-Biofarm 400 mg film-coated tablet), brand name Imatenil, Caucasian healthy volunteers in fed conditions. A single oral dose administration of the test or reference product was separated by 14-day washout period. The imatinib and its metabolite N-desmethyl imatinib concentrations were determined using a validated LC MS/MS method. The results of the single-dose study in healthy volunteers indicated that the film-coated tablets of Imatynib-Biofarm 100 mg and 400 mg film-coated tablets manufactured by Biofarm Sp. z o.o. (test products) are bioequivalent to those of Glivec 100 mg and 400 mg film-coated tablets manufactured by Novartis Pharma GmbH (reference products). Both products in the two doses of imatinib were well tolerated.

  4. Effect of Toys and Preoperative Visit on Reducing Children’s Anxiety and their Parents before Surgery and Satisfaction with the Treatment Process

    Directory of Open Access Journals (Sweden)

    Fatemeh Ghabeli

    2014-02-01

    Full Text Available Introduction: Hospital anxiety and surgery has an unpleasant and disturbing feeling for a child and his/her family. This study aimed to determine the effect of toys and visit in reducing children’s anxiety before the surgery and their mothers and satisfaction with the treatment process. Methods: This was a quasi-experimental study in posttest design with a control group. 60 children aged 3 to 8 years, who were undergoing ear, nose and throat surgery in Tabriz Amiralmomenin hospital, were chosen, and regarding their age and gender, were recruited into the control or experiment group. For the experiment group, the interventions before surgery were applied. The level of anxiety in children and parents was evaluated by Observation Scale of Behavioral Distress (OSBD-R and Spielberger State Anxiety Inventory (STAI. The level of parental satisfaction with the treatment process before being discharged from the hospital was evaluated by the process of treatment satisfaction questionnaire (PSQ-18. Data were analyzed by SPSS ver.13. Results: Mean anxiety scores of the children and mothers in the experimental group were lower than the control group. Mean maternal satisfaction score of the treatment process in the experimental group was higher than the mean scores of the control group. However, in the subscales of general satisfaction, interpersonal behavior, and financial aspects of satisfaction with treatment, no statistical significant difference was found between the experimental and control groups. Conclusion: Based on the findings, providing toys for children and informing the parents about medical information has a major effect in reducing children’s and other’s anxiety and increasing maternal satisfaction with the treatment process.

  5. Iron therapy for pre-operative anaemia.

    Science.gov (United States)

    Ng, Oliver; Keeler, Barrie D; Mishra, Amitabh; Simpson, Alastair; Neal, Keith; Brookes, Matthew J; Acheson, Austin G

    2015-12-22

    Pre-operative anaemia is common and occurs in up to 76% of patients. It is associated with increased peri-operative allogeneic blood transfusions, longer hospital lengths of stay and increased morbidity and mortality. Iron deficiency is one of the most common causes of this anaemia. Oral iron therapy has traditionally been used to treat anaemia but newer, safer parenteral iron preparations have been shown to be more effective in other conditions such as inflammatory bowel disease, chronic heart failure and post-partum haemorrhage. A limited number of studies look at iron therapy for the treatment of pre-operative anaemia. The aim of this Cochrane review is to summarise the evidence for use of iron supplementation, both enteral and parenteral, for the management of pre-operative anaemia. The objective of this review is to evaluate the effects of pre-operative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery. We ran the search on 25 March 2015. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic and EMBASE (Ovid), CINAHL Plus (EBSCO), PubMed, clinical trials registries, conference abstracts, and we screened reference lists. We included all randomised controlled trials (RCTs) which compared pre-operative iron monotherapy to placebo, no treatment, standard of care or another form of iron therapy for anaemic adults undergoing surgery. Anaemia was defined by haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females. Data were collected by two authors on the proportion of patients who receive a blood transfusion, amount of blood transfused per patient (units) and haemoglobin measured as continuous variables at pre-determined time-points: pre-treatment

  6. Survival of gastrointestinal stromal tumor patients in the imatinib era: life raft group observational registry

    Directory of Open Access Journals (Sweden)

    Call Jerry

    2012-03-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST, one of the most common mesenchymal tumors of the gastrointestinal tract, prior to routine immunohistochemical staining and the introduction of tyrosine kinase inhibitors, were often mistaken for neoplasms of smooth muscle origin such as leiomyomas, leiomyosarcomas or leiomyoblastomas. Since the advent of imatinib, GIST has been further delineated into adult- (KIT or PDGFRα mutations and pediatric- (typified by wild-type GIST/succinate dehydrogenase deficiencies types. Using varying gender ratios at age of diagnosis we sought to elucidate prognostic factors for each sub-type and their impact on overall survival. Methods This is a long-term retrospective analysis of a large observational study of an international open cohort of patients from a GIST research and patient advocacy's lifetime registry. Demographic and disease-specific data were voluntarily supplied by its members from May 2000-October 2010; the primary outcome was overall survival. Associations between survival and prognostic factors were evaluated by univariate Cox proportional hazard analyses, with backward selection at P Results Inflections in gender ratios by age at diagnosis in years delineated two distinct groups: above and below age 35 at diagnosis. Closer analysis confirmed the above 35 age group as previously reported for adult-type GIST, typified by mixed primary tumor sites and gender, KIT or PDGFRα mutations, and shorter survival times. The pediatric group ( Conclusions Pediatric- and adult-type GIST have been previously characterized in clinical settings and these observations confirm significant prognostic factors for each from a diverse real-world cohort. Additionally, these findings suggest that extra diligence be taken with "young adults" (aged 18-35 at diagnosis as pediatric-type GIST may present well beyond adolescence, particularly as these distinct sub-types have different causes, and consequently

  7. Synergy between proteasome inhibitors and imatinib mesylate in chronic myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Zheng Hu

    Full Text Available BACKGROUND: Resistance developed by leukemic cells, unsatisfactory efficacy on patients with chronic myeloid leukemia (CML at accelerated and blastic phases, and potential cardiotoxity, have been limitations for imatinib mesylate (IM in treating CML. Whether low dose IM in combination with agents of distinct but related mechanisms could be one of the strategies to overcome these concerns warrants careful investigation. METHODS AND FINDINGS: We tested the therapeutic efficacies as well as adverse effects of low dose IM in combination with proteasome inhibitor, Bortezomib (BOR or proteasome inhibitor I (PSI, in two CML murine models, and investigated possible mechanisms of action on CML cells. Our results demonstrated that low dose IM in combination with BOR exerted satisfactory efficacy in prolongation of life span and inhibition of tumor growth in mice, and did not cause cardiotoxicity or body weight loss. Consistently, BOR and PSI enhanced IM-induced inhibition of long-term clonogenic activity and short-term cell growth of CML stem/progenitor cells, and potentiated IM-caused inhibition of proliferation and induction of apoptosis of BCR-ABL+ cells. IM/BOR and IM/PSI inhibited Bcl-2, increased cytoplasmic cytochrome C, and activated caspases. While exerting suppressive effects on BCR-ABL, E2F1, and beta-catenin, IM/BOR and IM/PSI inhibited proteasomal degradation of protein phosphatase 2A (PP2A, leading to a re-activation of this important negative regulator of BCR-ABL. In addition, both combination therapties inhibited Bruton's tyrosine kinase via suppression of NFkappaB. CONCLUSION: These data suggest that combined use of tyrosine kinase inhibitor and proteasome inhibitor might be helpful for optimizing CML treatment.

  8. In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

    Directory of Open Access Journals (Sweden)

    P.B. Soares

    2013-01-01

    Full Text Available Imatinib mesylate (IM is used to treat chronic myeloid leukemia (CML because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM. The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM, using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells increased. At higher concentrations (15 µM, the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control. Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved.

  9. Doxorubicin Differentially Induces Apoptosis, Expression of Mitochondrial Apoptosis-Related Genes, and Mitochondrial Potential in BCR-ABL1-Expressing Cells Sensitive and Resistant to Imatinib

    Directory of Open Access Journals (Sweden)

    Ewelina Synowiec

    2015-01-01

    Full Text Available Imatinib resistance is an emerging problem in the therapy of chronic myeloid leukemia (CML. Because imatinib induces apoptosis, which may be coupled with mitochondria and DNA damage is a prototype apoptosis-inducing factor, we hypothesized that imatinib-sensitive and -resistant CML cells might differentially express apoptosis-related mitochondrially encoded genes in response to genotoxic stress. We investigated the effect of doxorubicin (DOX, a DNA-damaging anticancer drug, on apoptosis and the expression of the mitochondrial NADH dehydrogenase 3 (MT-ND3 and cytochrome b (MT-CYB in model CML cells showing imatinib resistance caused by Y253H mutation in the BCR-ABL1 gene (253 or culturing imatinib-sensitive (S cells in increasing concentrations of imatinib (AR. The imatinib-resistant 253 cells displayed higher sensitivity to apoptosis induced by 1 μM DOX and this was confirmed by an increased activity of executioner caspases 3 and 7 in those cells. Native mitochondrial potential was lower in imatinib-resistant cells than in their sensitive counterparts and DOX lowered it. MT-CYB mRNA expression in 253 cells was lower than that in S cells and 0.1 μM DOX kept this relationship. In conclusion, imatinib resistance may be associated with altered mitochondrial response to genotoxic stress, which may be further exploited in CML therapy in patients with imatinib resistance.

  10. Stability-indicating HPTLC determination of imatinib mesylate in bulk drug and pharmaceutical dosage form.

    Science.gov (United States)

    Vadera, N; Subramanian, G; Musmade, P

    2007-01-17

    A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of imatinib mesylate both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (6:4, v/v). The system was found to give compact spot for imatinib mesylate (R(f) value of 0.53+/-0.02). Densitometric analysis of imatinib mesylate was carried out in the absorbance mode at 276 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.9966+/-0.0013 with respect to peak area in the concentration range 100-1000 ng per spot. The mean value+/-S.D. of slope and intercept were 164.85+/-0.72 and 1168.3+/-8.26 with respect to peak area. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 10 and 30 ng per spot, respectively. Imatinib mesylate was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and heat conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and heat. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of imatinib mesylate in bulk drug and dosage forms.

  11. Structural identification of imatinib cyanide adducts by mass spectrometry and elucidation of bioactivation pathway.

    Science.gov (United States)

    Li, Austin C; Yu, Erya; Ring, Steven C; Chovan, James P

    2014-01-15

    Recent publications have reported that imatinib forms cyanide and methoxylamine adducts in vitro but without detail structural identification. The current work reports the identification of seven cyanide adducts that elucidate the bioactivation pathways and may provide hints for observed clinical adverse effects of the drug. Imatinib was incubated with human liver microsomal proteins in the presence of a NADPH-regeneration system and the trapping agents reduced GSH, potassium cyanide and methoxylamine. Samples were analyzed by high-performance liquid chromatography (HPLC) coupled with a LTQ-Orbitrap data collection system. Chemical structures were determined and/or postulated based on data-dependent high-resolution tandem mass spectrometric (MS(n)) exact mass measurements in both positive and negative scan modes, as well as in combination with hydrogen-deuterium exchange (HDX). GSH and methoxylamine conjugates were either not detected or were in insufficient quantities for characterization. However, seven cyanide conjugates were identified, indicating that the piperazine and p-toluidine partial structures in imatinib can become bioactivated and subsequently trapped by the nucleophile cyanide ion. The reactive intermediates were postulated as imine and imine-carbonyl conjugate (α,β-unsaturated) structures on the piperazine ring, and imine-methide on the p-toluidine partial structure. Chemical structures of seven cyanide adducts of imatinib have been identified or proposed based on high-resolution MS/MS data. Mechanisms for the formation of the conjugates were also proposed. The findings may help to understand the mechanism of hepatotoxicity of imatinib in humans. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Stability-Indicating HPTLC Determination of Imatinib Mesylate in Bulk Drug and Pharmaceutical Dosage

    Science.gov (United States)

    Musmade, P.; Vadera, N.; Subramanian, G.

    A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of imatinib mesylate both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminum plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (6:4, v/v). The system was found to give compact spot for imatinib mesylate (R f value of 0.53 ± 0.02). Densitometric analysis of imatinib mesylate was carried out in the absorbance mode at 276 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r 2 = 0.9966 ± 0.0013 with respect to peak area in the concentration range 100-1,000 ng per spot. The mean value ± SD of slope and intercept were 164.85 ± 0.72 and 1168.3 ± 8.26, respectively, with respect to peak area. The method was validated for precision, recovery, and robustness. The limits of detection and quantitation were 10 and 30 ng per spot, respectively. Imatinib mesylate was subjected to acid and alkali hydrolysis, and oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation, and heat conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation, and heat. Statistical analysis proves that the method is repeatable, selective, and accurate for the estimation of the said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of imatinib mesylate in bulk drug and dosage forms.

  13. Phase I study of gemcitabine, docetaxel and imatinib in refractory and relapsed solid tumors

    Science.gov (United States)

    Chugh, Rashmi; Karantza, Vassiliki; Mehnert, Janice; Moss, Rebecca A.; Savkina, Nelli; Stein, Mark N.; Baker, Laurence H.; Chenevert, Thomas; Poplin, Elizabeth A.

    2017-01-01

    Summary Purpose In a phase I study, the combination of gemcitabine and imatinib was well tolerated with broad anticancer activity. This phase I trial evaluated the triplet of docetaxel, gemcitabine and imatinib. Experimental Design Imatinib was administered at 400 mg daily on days 1–5, 8–12 and 15–19. Gemcitabine was started at 600 mg/m2 at a rate of 10 mg/min on days 3 and 10 and docetaxel at 30 mg/m2 on day 10, on a 21-day cycle. Diffusion and dynamic contrast-enhanced perfusion MRI was performed in selected patients. Results Twenty patients with relapsed/ refractory solid tumors were enrolled in this IRB-approved study. The mean age was 64, and mean ECOG PS was 1. Two patients were evaluated by diffusion/perfusion MRI. After two grade 3 hematological toxicities at dose level 1, the protocol was amended to reduce the dose of imatinib. MTDs were 600 mg/ m2 on days 3 and 10 for gemcitabine, 30 mg/ m2 on day 10 for docetaxel, and 400 mg daily on days 1–5 and 8–12 for imatinib. Dose limiting toxicities after one cycle were neutropenic fever, and pleural and pericardial effusions. The best response achieved was stable disease, for six cycles, in one patient each with mesothelioma and non small cell lung cancer (NSCLC) at the MTD. Two patients with NSCLC had stable disease for four cycles. Discussion An unexpectedly low MTD for this triplet was identified. Our results suggest drug-drug interactions that amplify toxicities with little evidence of improved tumor control. PMID:20697775

  14. Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial.

    Science.gov (United States)

    Gotta, V; Widmer, N; Decosterd, L A; Chalandon, Y; Heim, D; Gregor, M; Benz, R; Leoncini-Franscini, L; Baerlocher, G M; Duchosal, M A; Csajka, C; Buclin, T

    2014-12-01

    This study assessed whether a cycle of "routine" therapeutic drug monitoring (TDM) for imatinib dosage individualization, targeting an imatinib trough plasma concentration (C min) of 1,000 ng/ml (tolerance: 750-1,500 ng/ml), could improve clinical outcomes in chronic myelogenous leukemia (CML) patients, compared with TDM use only in case of problems ("rescue" TDM). Imatinib concentration monitoring evaluation was a multicenter randomized controlled trial including adult patients in chronic or accelerated phase CML receiving imatinib since less than 5 years. Patients were allocated 1:1 to "routine TDM" or "rescue TDM." The primary endpoint was a combined outcome (failure- and toxicity-free survival with continuation on imatinib) over 1-year follow-up, analyzed in intention-to-treat (ISRCTN31181395). Among 56 patients (55 evaluable), 14/27 (52 %) receiving "routine TDM" remained event-free versus 16/28 (57 %) "rescue TDM" controls (P = 0.69). In the "routine TDM" arm, dosage recommendations were correctly adopted in 14 patients (median C min: 895 ng/ml), who had fewer unfavorable events (28 %) than the 13 not receiving the advised dosage (77 %; P = 0.03; median C min: 648 ng/ml). This first target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" because of small patient number and surprisingly limited prescriber's adherence to dosage recommendations. Favorable outcomes were, however, found in patients actually elected for target dosing. This study thus shows first prospective indication for TDM being a useful tool to guide drug dosage and shift decisions. The study design and analysis provide an interesting paradigm for future randomized TDM trials on targeted anticancer agents.

  15. Preoperative assessment and optimization in periampullary and pancreatic cancer

    Directory of Open Access Journals (Sweden)

    S Myatra

    2011-01-01

    Full Text Available Perioperative management of pancreatic and periampullary cancer poses a considerable challenge to the pancreatic surgeon, anesthesiologist, and the intensive care team. The preoperative surgical evaluation of a pancreatic lesion aims to define the nature of the lesion (malignant or benign, stage the tumor, and to determine resectability or other non-surgical treatment options. Patients are often elderly and may have significant comorbidities and malnutrition. Obstructive jaundice may lead to coagulopathy, infection, renal dysfunction, and adverse outcomes. Routine preoperative biliary drainage can result in higher complication rates, and metal stents may be preferred over plastic stents in selected patients with resectable disease. Judicious use of antibiotics and maintaining fluid volume preoperatively can reduce the incidence of infection and renal dysfunction, respectively. Perioperative fluid therapy with hemodynamic optimization using minimally invasive monitoring may help improve outcomes. Careful patient selection, appropriate preoperative evaluation and optimization can greatly contribute to a favorable outcome after major pancreatic resections.

  16. The effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism

    OpenAIRE

    Yeliz Yilmaz; Kemal Erdinc Kamer; Orhan Ureyen; Erdem Sari; Turan Acar; Onder Karahalli

    2016-01-01

    Aim: To investigate the effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism. Material and methods: This controlled, randomized, prospective cohort was carried out on 40 patients who admitted for surgery due to hyperthyroidism. Cases were randomly assigned to receive either preoperative treatment with Lugol solution (Group 1) or no preoperative treatment with Lugol solution (Group 2). Group 3 (n = 10) consisted of healthy adults with no known hi...

  17. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Thomsen, Thordis; Villebro, Nete; Møller, Ann Merete

    2014-01-01

    : Randomized controlled trials that recruited people who smoked prior to surgery, offered a smoking cessation intervention, and measured preoperative and long-term abstinence from smoking or the incidence of postoperative complications or both outcomes. DATA COLLECTION AND ANALYSIS: The review authors......BACKGROUND: Smokers have a substantially increased risk of postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence, and surgery may constitute a unique opportunity for smoking cessation interventions. OBJECTIVES: The objectives of this review...... are to assess the effect of preoperative smoking intervention on smoking cessation at the time of surgery and 12 months postoperatively, and on the incidence of postoperative complications. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register in January 2014. SELECTION CRITERIA...

  18. Preoperative High-Dose Steroid Has Long-Term Beneficial Effects for Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Syuichi Tetsuka

    2013-01-01

    Full Text Available Previous studies addressing preoperative steroid treatment have revealed that control of myasthenia gravis (MG with steroids prior to surgery appeared to stabilize postoperative status. The purpose of our study was to clarify the clinical benefits of the preoperative programmed high-dose steroid treatment on the long-term outcomes of MG patients. We retrospectively reviewed the records of 171 MG patients who were followed up after undergoing thymectomy in our hospital between 1988 and 2006. One hundred and thirteen patients in the programmed treatment group had received preoperative steroid treatment, while 58 patients received no steroid treatment during the preoperative period. Clinical remission, which was defined as the achievement of the modified pharmacologic remission (PR for at least 1 year, and clinical benefits were compared between the two groups. With regard to the remission after thymectomy, Kaplan-Meier life-table curves for patients in the preoperative steroid treatment group versus those for patients in the no steroid preoperative treatment group revealed a significantly higher probability of the PR in the preoperative steroid treatment group (log-rank test, P<0.01. This study might be the first, as per our knowledge, to indicate that preoperative programmed high-dose steroid treatment has long-term beneficial effects for MG patients.

  19. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results

    Science.gov (United States)

    Giles, Francis J.; Bhalla, Kapil N.; Pinilla-Ibarz, Javier; Larson, Richard A.; Gattermann, Norbert; Ottmann, Oliver G.; Hochhaus, Andreas; Radich, Jerald P.; Saglio, Giuseppe; Hughes, Timothy P.; Martinelli, Giovanni; Kim, Dong-Wook; Shou, Yaping; Gallagher, Neil J.; Blakesley, Rick; Baccarani, Michele; Cortes, Jorge; le Coutre, Philipp D.

    2011-01-01

    Nilotinib is a potent selective inhibitor of the BCR-ABL tyrosine kinase approved for use in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP), and in CML-CP and CML-accelerated phase after imatinib failure. Nilotinib (400 mg twice daily) was approved on the basis of the initial results of this phase 2 open-label study. The primary study endpoint was the proportion of patients achieving major cytogenetic response (CyR). All patients were followed for ≥ 24 months or discontinued early. Of 321 patients, 124 (39%) continue on nilotinib treatment. Overall, 59% of patients achieved major CyR; this was complete CyR (CCyR) in 44%. Of patients achieving CCyR, 56% achieved major molecular response. CyRs were durable, with 84% of patients who achieved CCyR maintaining response at 24 months. The overall survival at 24 months was 87%. Adverse events were mostly mild to moderate, generally transient, and easily managed. This study indicates that nilotinib is effective, with a manageable safety profile, and can provide favorable long-term benefits for patients with CML-CP after imatinib failure. This trial was registered at www.clinicaltrials.gov as #NCT00109707. PMID:21098399

  20. [A female chronic myeloid leukemia patient who gave birth after stopping imatinib intentionally but who maintained a major molecular response with interferon].

    Science.gov (United States)

    Osawa, Tomohiro; Takahashi, Takeshi; Yasuda, Masahiro; Umeda, Michi; Nagaya, Katsuhiro; Tachi, Tomoya; Goto, Hideko; Kasahara, Senji; Teramachi, Hitomi; Goto, Chitoshi

    2015-04-01

    Imatinib was administrated to a 38-year-old woman with chronic myeloid leukemia(CML). A major molecular response (MMR)(≤5 copies/0.5 μgRNA in Amp-CML detected using the transcription mediated amplification/hybridization protection assay(TMA/HPA)method)was achieved in 18 months. She maintained MMR for 10 months, and wished to become pregnant. Imatinib was stopped intentionally because she wished to plan a pregnancy, but we prescribed interferon alpha (IFN-a)due to the likelihood of the CML recurring after pregnancy. The nausea caused by IFN-a was improved by administrating it during the night, and she gave birth to a healthy baby by a normal delivery, whilst maintaining MMR. In this case, IFN-a treatment gave good clinical results, the patient's prognosis was improved, and she could maintain a good quality of life. We consider this to be an informative example of IFN-a therapy for CML during pregnancy.

  1. Preoperative irradiation and cystectomy for bladder cancer.

    Science.gov (United States)

    Smith, J A; Batata, M; Grabstald, H; Sogani, P C; Herr, H; Whitmore, W F

    1982-03-01

    Between 1971 and 1974, 101 patients at Memorial Sloan-Kettering Cancer Center underwent planned integrated treatment for bladder cancer with 2000 rads by megavoltage delivered to the whole pelvis over five consecutive days followed by radical cystectomy within a week. The overall five-year survival rate was 39%; the hospital mortality rate was 2%. In the pelvis alone tumor recurred in 9% of the patients. These results support other studies demonstrating the efficacy of this and other regimens of preoperative irradiation and cystectomy.

  2. Surface analytical studies of maxillofacial implants: influence of the preoperational treatment and the human body on the surface properties of retrieved implants.

    Science.gov (United States)

    Kiss, Gábor; Sebők, Béla; Szabó, Péter J; Joób, Arpád F; Szabó, György

    2014-05-01

    In the present work, surface analytical investigation of unimplanted as well as retrieved pyrolytic carbon-covered carbon/carbon composite implants and Ti osteosynthesis plates is reported. The Ti plates were covered by a 200-nm-thick, anodically and thermally formed TiO2 layer. Our results suggest that although the oxide layer on the Ti miniplates remained stable during the time spent in the human body, there is still material transport between the implant and the human body. In case of the carbon/carbon composite implants, damage of the carbon fibers constituting the material was found on one side of the sterile implant and attributed to the manufacturing process. The NaCl crystals originally present on the surface of the sterile material disappeared during the time spent in the human body. As a result of the interaction with the human body, a new surface layer (mainly constituted of carbon) appeared on the implant. The results indicate that both the time spent in the human organism and the preparation of the implants before operation can have detectable effects on the investigated surface properties. Surface analytical investigations could therefore provide information not only about the biocompatibility of these materials but also about the effect of their treatment before operation.

  3. Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

    Directory of Open Access Journals (Sweden)

    Fiorentini Giammaria

    2006-01-01

    Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

  4. Anxiety in preoperative anesthetic procedures.

    Science.gov (United States)

    Valenzuela Millán, Jaquelyn; Barrera Serrano, José René; Ornelas Aguirre, José Manuel

    2010-01-01

    Preoperative anxiety is a common and poorly evaluated condition in patients who will undergo an anesthetic and surgical intervention. The objective of this study was to determine the prevalence of anxiety in a group of patients undergoing elective surgery, as assessed by the Amsterdam Anxiety Preoperative and Information (AAPI) scale. We studied 135 patients scheduled for elective surgery applying the AAPI scale 24 h before the surgical procedure to evaluate the presence of anxiety and patient characteristics. A descriptive analysis with mean +/- standard deviation for categorical variables was done. For intragroup differences, chi(2) test was used. Pearson correlation for the association between anxiety and postoperative complications was carried out. A value of p =0.05 was considered significant. One hundred six patients were surgically treated, 88% were female (average age 44 +/- 12 years). Some degree of preoperative anxiety was present in 72 patients (76%; p = 0.001) with a grade point average on the AAPI scale equal to 17 +/- 7 points, of which 95 (70%, OR = 5.08; p = 0.002) were females. Results of this study suggest the presence of high levels of preoperative anxiety in patients scheduled for elective surgery. The origin of the anxiety appears to be related to many factors that can be evaluated in pre-anesthetic consultation. Further study is needed to prevent the presence of this disorder.

  5. The importance of preoperative diagnosis of blister aneurysms.

    Science.gov (United States)

    Russin, Jonathan J; Kramer, Daniel R; Thomas, Debi; Hasson, Denise; Liu, Charles Y; Amar, Arun P; Mack, William J; Giannotta, Steven L

    2015-09-01

    We describe a series of 14 surgical blister aneurysm (BA) patients and compare outcomes in those with known cerebral BA to those lacking preoperative BA diagnosis/recognition. BA are broad, fragile, pathologic dilatations of the intracranial arteries. They have a low prevalence but are associated with substantially higher surgical morbidity and mortality rates than saccular aneurysms. A confirmed, preoperative BA diagnosis can alter operative management and technique. We performed a retrospective review of prospectively collected data on aneurysm patients undergoing surgery at a major academic institution. All patients from 1990 to 2011 with a postoperative BA diagnosis were included. Chart reviews were performed to identify patients with preoperative BA diagnoses and collect descriptive data. We identified 14 patients, 12 of whom presented with subarachnoid hemorrhage. The age of the cohort (mean ± standard deviation: 41.8 ± 13.9 years) was lower than that generally reported for saccular aneurysm populations. Preoperatively diagnosed BA had an intraoperative rupture (IOR) rate of 28.6% (2/7) compared to a 57.1% (4/7) rate in the undiagnosed patients. The mortality rate in the preoperatively diagnosed cohort was 14.3% (1/7) while that of the undiagnosed group was 42.8% (3/7). BA remain a diagnostic and treatment challenge with morbidity and mortality rates exceeding those of saccular aneurysms. Preoperative BA diagnosis may decrease IOR and mortality rates and improve patient outcomes.

  6. Imatinib mesylate induces mitochondria-dependent apoptosis and inhibits invasion of human pigmented villonodular synovitis fibroblast-like synovial cells.

    Science.gov (United States)

    Chen, Kang; Ren, Qiao; Han, Xiao-Rui; Zhang, Xiao-Nan; Wei, Bo; Bai, Xi-Zhuang

    2016-01-01

    Pigmented villonodular synovitis (PVNS) is a rare sarcoma-like disorder characterized by synovial lesions proliferation and invasion to articular cartilage for which no effective treatments are available. Imatinib mesylate (IM) is known to exert antitumor activity in some tumors, but its effects on PVNS fibroblast-like synoviocytes (PVNS-FLS) and the specific mechanism involved remain to be established. In the present study, the in vitro effects of IM on cell proliferation and survival rates were investigated in PVNS-FLS. Apoptosis induction was assessed via acridine orange/ethidium bromide (AO)/(EB) and Annexin V/PI staining as well as western blotting. The invasion ability of PVNS-FLS was evaluated by Transwell invasion chambers. IM significantly inhibited survival and invasion ability of PVNS-FLS in a dose- and time-dependent manner. The drug-treated cell groups exhibited markedly higher apoptosis, which was blocked upon pretreatment with the specific caspase-9 inhibitor Z-LEHD-FMK. Expression of cleaved caspase-9 was significantly increased and the Bcl-2 family and caspase-3 were activated following treatment with IM. Our results collectively demonstrated that IM has a strong antiproliferative effect on PVNS-FLS in vitro, attributable to induction of mitochondrial-dependent apoptosis in association with activation of caspase-9/-3 and the Bcl-2/Bax family, and exhibits significant inhibition on the invasion ability of PVNS-FLS, suggesting that IM may be useful as a novel treatment of this disease.

  7. Association of Preoperative Anemia With Postoperative Mortality in Neonates.

    Science.gov (United States)

    Goobie, Susan M; Faraoni, David; Zurakowski, David; DiNardo, James A

    2016-09-01

    . Multivariable regression analysis demonstrated that preoperative anemia is an independent risk factor for mortality (OR, 2.62; 95% CI, 1.51-4.57) in neonates. The prevalence of postoperative in-hospital mortality was significantly higher in neonates with a preoperative hematocrit level less than 40%; being 7.5% (95% CI, 1%-10%) vs 1.4% (95% CI, 0%-4%) for preoperative hematocrit levels 40%, or greater. The relationship between anemia and in-hospital mortality was confirmed in our validation cohort (National Surgical Quality Improvement Program 2014). To our knowledge, this is the first study to define the incidence of preoperative anemia in neonates, the incidence of postoperative in-hospital mortality in neonates, and the association between preoperative anemia and postoperative mortality in US hospitals. Timely diagnosis, prevention, and appropriate treatment of preoperative anemia in neonates might improve survival.

  8. Imatinib induced melasma-like pigmentation: Report of five cases and review of literature

    Directory of Open Access Journals (Sweden)

    Sneha Ghunawat

    2016-01-01

    Full Text Available Imatinib mesylate is a cytotoxic agent that targets tyrosine kinase. Common side effects of this drug include nausea, edema and maculopapular rash. Hypopigmentation is a commonly reported side effect of this drug while hyperpigmentation has rarely been described. We describe five cases of melasma-like pigmentation induced by this anti-cancer drug. Four of the patients were diagnosed with gastrointestinal stromal tumor while one had chronic myeloid leukemia. Patients received imatinib mesylate in a dose of 400 mg daily. Over an average period of 3 months, well defined hyperpigmented macules appeared over the convexities of the face. One of the patients also developed similar pigmentation on the forearm. Other causes of hyperpigmentation were excluded in each patient.

  9. Imatinib induced melasma-like pigmentation: Report of five cases and review of literature.

    Science.gov (United States)

    Ghunawat, Sneha; Sarkar, Rashmi; Garg, Vijay Kumar

    2016-01-01

    Imatinib mesylate is a cytotoxic agent that targets tyrosine kinase. Common side effects of this drug include nausea, edema and maculopapular rash. Hypopigmentation is a commonly reported side effect of this drug while hyperpigmentation has rarely been described. We describe five cases of melasma-like pigmentation induced by this anti-cancer drug. Four of the patients were diagnosed with gastrointestinal stromal tumor while one had chronic myeloid leukemia. Patients received imatinib mesylate in a dose of 400 mg daily. Over an average period of 3 months, well defined hyperpigmented macules appeared over the convexities of the face. One of the patients also developed similar pigmentation on the forearm. Other causes of hyperpigmentation were excluded in each patient.

  10. Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic leukaemia.

    Science.gov (United States)

    Curtis, Claire E; Grand, Francis H; Musto, Pellegrino; Clark, Andrew; Murphy, John; Perla, Gianni; Minervini, Maria M; Stewart, Janet; Reiter, Andreas; Cross, Nicholas C P

    2007-07-01

    We identified two patients with a t(2;4)(p24;q12) and a t(4;12)(q2?3;p1?2), respectively, in association with BCR-ABL and FIP1L1-PDGFRA negative chronic eosinophilic leukaemia. Molecular analysis revealed a novel STRN-PDGFRA fusion for the t(2;4) and ETV6-PDGFRA for the t(4;12). The fusions were confirmed by specific amplification of the genomic breakpoints, reverse transcription polymerase chain reaction and fluorescence in situ hybridisation. Both patients were treated with imatinib and, following a rapid haematological response, achieved cytogenetic remission and a major molecular response. In conclusion, PDGFRA fuses to diverse partner genes in myeloid disorders. Identification of these fusions is important as they are particularly sensitive to imatinib.

  11. [Nilotinib in patients with chronic myeloid leukemia without response to imatinib].

    Science.gov (United States)

    Báez-de la Fuente, Enrique; Arellano-Severiano, Baltazar

    2014-01-01

    INTRODUCCIÓN: la resistencia e intolerancia al imatinib en pacientes con leucemia mieloide crónica requiere el uso de otros fármacos, como el nilotinib. El objetivo de este informe es presentar los resultados obtenidos en un grupo de pacientes con leucemia mieloide crónica que recibió tratamiento de segunda línea con nilotinib. MÉTODOS: se incluyeron 16 pacientes con diagnóstico de leucemia mieloide crónica que recibieron tratamiento de segunda línea con nilotinib, después de que no respondieron adecuadamente al imatinib. El cambio de fármaco se debió a intolerancia, resistencia o progresión de la leucemia.

  12. Prognostic significance of preoperative fibrinogen in patients with colon cancer.

    Science.gov (United States)

    Sun, Zhen-Qiang; Han, Xiao-Na; Wang, Hai-Jiang; Tang, Yong; Zhao, Ze-Liang; Qu, Yan-Li; Xu, Rui-Wei; Liu, Yan-Yan; Yu, Xian-Bo

    2014-07-14

    To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1(st) 2005 to June 1(st) 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P TNM stage, mGPS score, CEA, and AFP levels correlated with both OS and DFS. Preoperative fibrinogen levels can serve as an independent prognostic marker to evaluate patient response to colon cancer treatment.

  13. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) - the first trial of a German version

    OpenAIRE

    Berth, H; Petrowski, K; Balck, F

    2007-01-01

    Objective: Preoperative anxiety influences the result of the treatment in patients. To assess preoperative anxiety the Amsterdam Preoperative Anxiety and Information Scale (APAIS) was developed. The APAIS measures anxiety and the need-for-information with 6 items, with good reliability and validity. This article presents the first test of the German version of this screening instrument.Methods: The German version of the APAIS was tested on 68 patients questioned before surgery on the lower...

  14. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) - the first trial of a German version

    OpenAIRE

    Berth, Hendrik; Petrowski, Katja; Balck, Friedrich

    2007-01-01

    Objective: Preoperative anxiety influences the result of the treatment in patients. To assess preoperative anxiety the Amsterdam Preoperative Anxiety and Information Scale (APAIS) [1] was developed. The APAIS measures anxiety and the need-for-information with 6 items, with good reliability and validity. This article presents the first test of the German version of this screening instrument. Methods: The German version of the APAIS was tested on 68 patients questioned before surgery on the low...

  15. Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model.

    Science.gov (United States)

    Maj, Ewa; Filip-Psurska, Beata; Świtalska, Marta; Kutner, Andrzej; Wietrzyk, Joanna

    2015-11-13

    In previous papers, we presented data on studies on the anticancer activity of the vitamin D₃ analogs, named PRI-2191 and PRI-2205, in different cancer models. In this study, we showed the improved antiproliferative activity of a combination of imatinib mesylate (Gleevec, GV) and cytostatic agents in in vitro studies, when used with a third compound, namely PRI-2191, in an A549 human lung cancer model. Furthermore, we analyzed the influence of both PRI-2191, as well as PRI-2205 on the anticancer activity of GV in mice bearing A549 tumors. The route of PRI-2191 analog administration showed a significant impact on the outcome of GV treatment: subcutaneous injection was more efficient and less toxic than oral gavage. Moreover, both vitamin D compounds increased the anticancer activity of GV; however, they might also potentiate some adverse effects. We also evaluated in tumor tissue the expression of VEGF, PDGF-BB, vitamin D receptor, CYP27B1, CYP24, p53 and Bcl-2, as well as PDGF receptors: α and β. We observed the upregulation of p53 expression and the downregulation of Bcl-2, as well as VEGF in A549 tumors as a result of the tested treatment. However, vitamin D analogs did not significantly influence the expression of these proteins.

  16. Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model

    Science.gov (United States)

    Maj, Ewa; Filip-Psurska, Beata; Świtalska, Marta; Kutner, Andrzej; Wietrzyk, Joanna

    2015-01-01

    In previous papers, we presented data on studies on the anticancer activity of the vitamin D3 analogs, named PRI-2191 and PRI-2205, in different cancer models. In this study, we showed the improved antiproliferative activity of a combination of imatinib mesylate (Gleevec, GV) and cytostatic agents in in vitro studies, when used with a third compound, namely PRI-2191, in an A549 human lung cancer model. Furthermore, we analyzed the influence of both PRI-2191, as well as PRI-2205 on the anticancer activity of GV in mice bearing A549 tumors. The route of PRI-2191 analog administration showed a significant impact on the outcome of GV treatment: subcutaneous injection was more efficient and less toxic than oral gavage. Moreover, both vitamin D compounds increased the anticancer activity of GV; however, they might also potentiate some adverse effects. We also evaluated in tumor tissue the expression of VEGF, PDGF-BB, vitamin D receptor, CYP27B1, CYP24, p53 and Bcl-2, as well as PDGF receptors: α and β. We observed the upregulation of p53 expression and the downregulation of Bcl-2, as well as VEGF in A549 tumors as a result of the tested treatment. However, vitamin D analogs did not significantly influence the expression of these proteins. PMID:26580599

  17. Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model

    Directory of Open Access Journals (Sweden)

    Ewa Maj

    2015-11-01

    Full Text Available In previous papers, we presented data on studies on the anticancer activity of the vitamin D3 analogs, named PRI-2191 and PRI-2205, in different cancer models. In this study, we showed the improved antiproliferative activity of a combination of imatinib mesylate (Gleevec, GV and cytostatic agents in in vitro studies, when used with a third compound, namely PRI-2191, in an A549 human lung cancer model. Furthermore, we analyzed the influence of both PRI-2191, as well as PRI-2205 on the anticancer activity of GV in mice bearing A549 tumors. The route of PRI-2191 analog administration showed a significant impact on the outcome of GV treatment: subcutaneous injection was more efficient and less toxic than oral gavage. Moreover, both vitamin D compounds increased the anticancer activity of GV; however, they might also potentiate some adverse effects. We also evaluated in tumor tissue the expression of VEGF, PDGF-BB, vitamin D receptor, CYP27B1, CYP24, p53 and Bcl-2, as well as PDGF receptors: α and β. We observed the upregulation of p53 expression and the downregulation of Bcl-2, as well as VEGF in A549 tumors as a result of the tested treatment. However, vitamin D analogs did not significantly influence the expression of these proteins.

  18. [Pregnancy and myeloid leukemia treated with imatinib. Development and monitoring of a patient].

    Science.gov (United States)

    Báez-de la Fuente, Enrique; Arellano-Severiano, Baltazar

    2014-01-01

    INTRODUCCIÓN: el tratamiento con imatinib ha modificado la historia natural de la leucemia mieloide crónica, y ha permitido que las mujeres con este padecimiento puedan embarazarse. El objetivo de este reporte es describir el curso y desenlace de un embarazo en una paciente con diagnóstico previo de leucemia mieloide crónica, que recibía tratamiento con imatinib. CASO CLÍNICO: mujer de 32 años con leucemia mieloide crónica de 11 años de evolución. Al diagnóstico se inició tratamiento estándar, pero debido a poca adherencia terapéutica, a los dos años se le prescribió imatinib. Debido al deseo de procrear, la paciente decidió suspender el medicamento. Un mes después acudió a la consulta con amenorrea de seis semanas de evolución; se confirmó embarazo. Durante 10 meses que permaneció sin tratamiento, no tuvo síntomas de progresión de la leucemia. El embarazo se interrumpió por cesárea a las 35.5 semanas de gestación. El neonato aparentemente se encontraba sano. En el transcurso del puerperio quirúrgico, la paciente acudió a consulta; los resultados de la biometría hemática indicaron hemoglobina de 8.7 g/dL, hematócrito de 25 %, leucocitos de 22 000/mL y plaquetas de 170 000/mL. Ese día se reinició tratamiento con 600 mg/día de imatinib.

  19. Preoperative workup to assess indication for laparoscopic treatment in gastroesophageal reflux disease Aseguramiento preoperatorio en la indicación de tratamiento laparoscópico en la enfermedad por reflujo gastroesofágico

    Directory of Open Access Journals (Sweden)

    S. Pérez-Holanda

    2008-07-01

    Full Text Available Introduction and objectives: antireflux surgery performed by an experienced surgeon is a maintenance option for patients with well-documented gastroesophageal reflux disease (GERD. Well-documented GERD is difficult to find, as GERD is a multifactorial disease in which the gastroesophageal junction, with its special anatomical and functional components, is important. In order to examine patient preoperative workups, and their indication for surgical treatment in GERD, we retrospectively studied patients who underwent a laparoscopic antireflux procedure. Methods: preoperative workups in patients from our health care area who underwent a laparoscopic antireflux procedure from December 1997 to February 2007 were retrospectively analyzed. Data related to epidemiological findings, symptoms, morphologic and functional evaluation, medical therapy, and indication for surgical treatment were recorded and statistically analyzed by means of a bivariate test. Differences were significant when the p value was equal to or less than 0.05. Results: 100 patients (50 % female, 51.31 ± 13.53 years of age underwent a laparoscopic antireflux surgery after 56.47 ± 61.33 months with symptoms. Ninety-five percent of patients had an anatomical abnormality. The pH monitoring test diagnosed three quarters of cases. The most frequent indication for GERD treatment was persistent or recurrent esophagitis despite adequate medical treatment (52 cases. Conclusions: based on our preoperative workup, as described, 100 percent of subjects were well documented and diagnosed with GERD (both non-erosive reflux disease and erosive reflux disease, and their indication for laparoscopic treatment was retrospectively assessed in 94% of cases.Introducción y objetivos: la cirugía antirreflujo realizada por un cirujano experto es una opción para el tratamiento de mantenimiento para el paciente con enfermedad por reflujo gastroesofágico (ERGE bien documentada. La "buena documentaci

  20. Dedifferentiation in Gastrointestinal Stromal Tumor to an Anaplastic KIT Negative Phenotype – a Diagnostic Pitfall. Morphologic and Molecular Characterization of 8 Cases Occurring either de-novo or after Imatinib Therapy

    Science.gov (United States)

    Antonescu, Cristina R; Romeo, Salvatore; Zhang, Lei; Nafa, Khedoudja; Hornick, Jason L.; Nielsen, G. Petur; Mino-Kenudson, Mari; Huang, Hsuan-Ying; Mosquera, Juan-Miguel; Dei Tos, Paolo A; Fletcher, Christopher D.M.

    2013-01-01

    Most GISTs can be recognized by their monotonous cytologic features and overexpression of KIT oncoprotein. Altered morphology and loss of CD117 reactivity has been described previously after chronic imatinib treatment; however, this phenomenon has not been reported in imatinib-naïve tumors. Eight patients with abrupt transition from a classic CD117-positive spindle cell GIST to an anaplastic CD117-negative tumor were investigated for underlying molecular mechanisms of tumor progression. Pathologic and molecular analysis was performed on each of the two components. Genomic DNA PCR for KIT, PDGFRA, BRAF and KRAS hot spot-mutations and FISH for detecting KIT gene copy number alterations were performed. TP53 mutational analysis was performed in 5 cases. There were 7 males and 1 female, with an age range of 23–65 years. Five of the primary tumors were located in the stomach, while one case each originated in small bowel, colon and rectum. In 3 patients, the dedifferentiated component occurred in the setting of imatinib-resistance, while the remaining 5 occurred de novo. The dedifferentiated component had an anaplastic appearance, including one angiosarcomatous phenotype, with high mitotic activity and necrosis, and showed complete loss of CD117 (8/8) and CD34 (5/8) expression, and de novo expression of either cytokeratin (4/8) or desmin (1/8). There was no difference in the KIT genotype between the two components. However, two imatinib-resistant tumors showed co-existence of KIT exon 11 and exon 13 mutations. FISH showed loss of one KIT gene in 3 cases and low level amplification of KIT in 2 other cases in the CD117-negative component, compared to the CD117-positive area. TP53 mutation was identified in 1/5 cases tested, being present in both components. In summary, dedifferentiation in GIST may occur either de novo or after chronic imatinib exposure and can represent a diagnostic pitfall. This phenomenon is not related to additional KIT mutations, but might be

  1. Preoperative cryotherapy use in anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Koyonos, Loukas; Owsley, Kevin; Vollmer, Emily; Limpisvasti, Orr; Gambardella, Ralph

    2014-12-01

    Unrelieved postoperative pain may impair rehabilitation, compromise functional outcomes, and lead to patient dissatisfaction. Preemptive multimodal analgesic techniques may improve outcomes after surgery. We hypothesized that patients using preoperative cryotherapy plus a standardized postoperative treatment plan will have lower pain scores and require less pain medication compared with patients receiving a standardized postoperative treatment plan alone after arthroscopically assisted anterior cruciate ligament reconstruction (ACLR). A total of 53 consecutive patients undergoing arthroscopically assisted ACLR performed by one of seven surgeons were randomly assigned to one of two groups. Group 1 received no preoperative cryotherapy and group 2 received 30 to 90 minutes of preoperative cryotherapy to the operative leg using a commercial noncompressive cryotherapy unit. Visual analog scale pain scores and narcotic use were recorded for the first 4 days postoperatively. Total hours of cold therapy and continuous passive motion (CPM) use and highest degree of flexion achieved were recorded as well. Group 1 consisted of 26 patients (15 allograft Achilles tendon and 11 autograft bone patellar tendon bone [BPTB]), and group 2 consisted of 27 patients (16 allograft Achilles tendon and 11 autograft BPTB). Group 2 patients reported less pain (average 1.3 units, p cryotherapy, hours of CPM use, or maximum knee flexion achieved. Complications did not occur in either group. This is the first report we are aware of showing the postoperative effects of preoperative cryotherapy. Our results support the safety and efficacy of preoperative cryotherapy in a multimodal pain regimen for patients undergoing ACL reconstruction.

  2. [Preoperative fasting guidelines: an update].

    Science.gov (United States)

    López Muñoz, A C; Busto Aguirreurreta, N; Tomás Braulio, J

    2015-03-01

    Anesthesiology societies have issued various guidelines on preoperative fasting since 1990, not only to decrease the incidence of lung aspiration and anesthetic morbidity, but also to increase patient comfort prior to anesthesia. Some of these societies have been updating their guidelines, as such that, since 2010, we now have 2 evidence-based preoperative fasting guidelines available. In this article, an attempt is made to review these updated guidelines, as well as the current instructions for more controversial patients such as infants, the obese, and a particular type of ophthalmic surgery. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Thomsen, Thordis; Villebro, Nete; Møller, Ann Merete

    2010-01-01

    and keywords (surgery) or (operation) or (anaesthesia) or (anesthesia). MEDLINE, EMBASE and CINAHL were also searched, combining tobacco- and surgery-related terms. Most recent search April 2010. Selection criteria Randomized controlled trials that recruited people who smoked prior to surgery, offered......Background Smokers have a substantially increased risk of postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence, and surgery may constitute a unique opportunity for smoking cessation interventions. Objectives The objective of this review...... was to assess the effect of preoperative smoking intervention on smoking cessation at the time of surgery and 12 months postoperatively and on the incidence of postoperative complications. Search strategy The specialized register of the Cochrane Tobacco Addiction Group was searched using the free text...

  4. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Thomsen, Thordis; Villebro, N.; Møller, Ann Merete;

    2010-01-01

    Background Smokers have a substantially increased risk of postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence, and surgery may constitute a unique opportunity for smoking cessation interventions. Objectives The objective of this review...... was to assess the effect of preoperative smoking intervention on smoking cessation at the time of surgery and 12 months postoperatively and on the incidence of postoperative complications. Search strategy The specialized register of the Cochrane Tobacco Addiction Group was searched using the free text......; pooled RR 10.76 (95% confidence interval (CI) 4.55 to 25.46, two trials) and RR 1.41 (95% CI 1.22 to 1.63, five trials) respectively. Four trials evaluating the effect on long-term smoking cessation found a significant effect; pooled RR 1.61 (95% CI 1.12 to 2.33). However, when pooling intensive...

  5. BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: using guidelines to make rational treatment choices.

    Science.gov (United States)

    Kantarjian, Hagop; Cortes, Jorge

    2008-03-01

    The success of the BCR-ABL tyrosine kinase inhibitor (TKI) imatinib in improving prognosis in chronic myeloid leukemia (CML) has led to its wide use as first-line therapy at a standard dose of 400 mg daily. As more patients have undergone therapy, the development of molecular and clinical resistance to imatinib has raised further therapeutic challenges. The 2 main approaches to overcoming resistance are imatinib dose escalation and the use of alternative more potent TKIs, such as dasatinib or nilotinib. The phase II SRC/ABL Tyrosine Kinase Inhibition Activity Research Trials (START) of dasatinib have established dasatinib as potent and effective in overcoming imatinib resistance or intolerance in all phases of CML. The most recent treatment guidelines by the National Comprehensive Cancer Network now contain recommendations for using dasatinib in this setting. The issue of when to change from imatinib to an alternative agent in preference to imatinib dose escalation is keenly debated, particularly as new clinical evidence emerges, which highlights the importance of achieving early cytogenetic and molecular responses for a good long-term outcome. Identifying patients in whom a change to dasatinib or nilotinib is more appropriate than imatinib dose escalation is therefore important.

  6. Preoperative chemoradiotherapy for locally advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Pepek Joseph M

    2013-01-01

    Full Text Available Abstract Background To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT for gastric cancer. Methods Patients with gastroesophageal (GE junction (Siewert type II and III or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS, local control (LC and disease-free survival (DFS were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Results Forty-eight patients were included. Most (73% had proximal (GE junction, cardia and fundus tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75% underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Conclusions Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

  7. Pregnancy outcomes in patients with chronic myeloid leukemia treated with imatinib mesylate: short report from a developing country.

    Science.gov (United States)

    Iqbal, Javaid; Ali, Zafar; Khan, Aruj-Un-Nisa; Aziz, Zeba

    2014-09-01

    Treatment of chronic myeloid leukemia (CML) is challenging in patients who want to conceive. We followed 809 patients with CML treated with imatinib mesylate (IM). We observed outcomes in 90 pregnancies from 61 patients (21 females, 40 males) who conceived while on IM. Information was obtained on duration of exposure to IM, pregnancy termination and congenital abnormalities. Hematologic and cytogenetic responses were also recorded. Twenty-eight pregnancies occurred among females, while 62 were reported from male patients. Among female patients, 19 (67.9%) pregnancies were uneventful while six (21.4%) ended in adverse events. Only 12 (57%) females reported their pregnancies. Three (4.4%) adverse events were reported from male patients. Pregnancy is an important part of life in our young patients due to cultural and societal pressures. It is paramount to counsel pregnant patients to switch to drugs with no adverse effect on the developing fetus. However, lack of communication is a major factor preventing physicians from counseling patients about conception.

  8. Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors

    Science.gov (United States)

    Cortes, Jorge E.; Kim, Dong-Wook; Khoury, H. Jean; Brümmendorf, Tim H.; Porkka, Kimmo; Martinelli, Giovanni; Durrant, Simon; Leip, Eric; Kelly, Virginia; Turnbull, Kathleen; Besson, Nadine; Gambacorti-Passerini, Carlo

    2014-01-01

    Bosutinib is an oral, dual SRC/ABL tyrosine kinase inhibitor (TKI) with clinical activity in Philadelphia chromosome–positive (Ph+) leukemia. We assessed the safety and tolerability of bosutinib 500 mg per day in a phase 1/2 study in chronic-phase (CP) chronic myeloid leukemia (CML) or advanced Ph+ leukemia following resistance/intolerance to imatinib and possibly other TKIs. Patient cohorts included second-line CP CML (n = 286), third-/fourth-line CP CML (n = 118), and advanced leukemia (n = 166). Median bosutinib duration was 11.1 (range, 0.03-83.4) months. Treatment-emergent adverse events (TEAEs) in each cohort were primarily gastrointestinal (diarrhea [86%/83%/74%], nausea [46%/48%/48%], and vomiting [37%/38%/43%]). Diarrhea presented early, with few (8%) patients experiencing grade 3/4 events; dose reduction due to diarrhea occurred in 6% of affected patients. Grade 3/4 myelosuppression TEAEs were reported in 41% of patients; among affected patients, 46% were managed with bosutinib interruption and 32% with dose reduction. Alanine aminotransferase elevation TEAEs occurred in 17% of patients (grade 3/4, 7%); among patients managed with dose interruption, bosutinib rechallenge was successful in 74%. Bosutinib demonstrated acceptable safety with manageable toxicities in Ph+ leukemia. This trial (NCT00261846) was registered at www.ClinicalTrials.gov (this manuscript is based on a different data snapshot from that in ClinicalTrials.gov). PMID:24345751

  9. Do psychological interventions reduce preoperative anxiety?

    Science.gov (United States)

    Renouf, Tessa; Leary, Alison; Wiseman, Theresa

    The systematic review investigates whether, during preoperative assessments, nurse-delivered psychological interventions reduce anxiety levels preoperatively for patients undergoing elective surgery. Seventeen studies met the inclusion criteria for data extraction and in-depth critiquing. Of these, two were discarded due to lack of validity, while the remaining studies were organised thematically in a narrative synthesis, generating two principal results: patients' preoperative anxieties were lowered by nurse-delivered general preoperative psychological interventions; and patients valued individualised preoperative interventions delivered by nurses. However, the single oncology study in the review showed an elevation in preoperative anxiety, regardless of intervention, and highlights the need for more research in this under-reviewed area. In the meantime, the authors believe that service improvements should be implemented to ensure that, where possible, psychological preoperative interventions are individualised.

  10. CLINICAL AND BIOLOGICAL BEHAVIOR OF NEUROGENIC TUMOR AFTER PREOPERATIVE CHEMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    Gao Jiechun; Dong Kuiran; Jing Baixiang

    1998-01-01

    Objective: To study the significance of preoperative chemotherapy for the treatment of neurogenic tumor in children. Methods: VMA, MYCN gene and DNA content of 21 cases of neuroblastoma treated with preoperative chemotherapy were studied with a control group. Results: Resection rate was 95.5%. Mean survival time was 28.1±10.2 months, which was significantly higher than the control group (8.8±6.8 months, P<0.01).Post chemotherapeutic VMA was lower. DNA index was also reduced and the percentage of cells in G0+G1 phases was elevated. The MYCN expression was suppressed.Conclusion: Preoperative chemotherapy can induce the apoptosis of neurogenic tumor cells and inhibit its proliferative activity.

  11. Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Li, E-mail: liuli029@yahoo.cn [Department of Hematology, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Wang, Sitao; Chen, Renan; Wu, Yanlan; Zhang, Bei; Huang, Siyong; Zhang, Jingyi; Xiao, Fang; Wang, Meng; Liang, Yingmin [Department of Hematology, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Increased c-myc expression in imatinib resistant CML cells. Black-Right-Pointing-Pointer c-myc contributes the imatinib resistance in CML cells. Black-Right-Pointing-Pointer c-myc transcriptionally reduces the expression of miR-144/451 in K562R cells. Black-Right-Pointing-Pointer Restoration of miR-144/451 reverses the resistance of K562R cells to imatinib. -- Abstract: Imatinib resistance remains the big hurdle for CML therapy. Previous study reveals that c-myc is important for bcr-abl CML cell proliferation, while its role in imatinib resistance is largely unknown. In this study, we first found that c-myc expression is upregulated in imatinib resistant K562R cells, which in turn enhances the expression of miR-144/451. Knockdown of c-myc or restoration of miR-144/451 in the K562R cells sensitizes K562R cells to imatinib therapy. Our study here reveals an regulatory pathway between myc and miR-144/451 and highlights that targeting either myc or miR-144/451 might be valuable for eliminating the imatinib resistant CML cells.

  12. Two different point mutations in ABL gene ATP-binding domain conferring Primary Imatinib resistance in a Chronic Myeloid Leukemia (CML patient: A case report

    Directory of Open Access Journals (Sweden)

    Iqbal Zafar

    2004-01-01

    Full Text Available Imatinib (Gleevec is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance.

  13. Preoperative localization in primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sanson; Kitamura, Hiroyuki; Takagita, Shin-ichi; Maetani, Toshiki; Iwahashi, Yuka; Miyazaki, Masakazu; Yamamoto, Norio [Tenri Hospital, Nara (Japan)

    1998-04-01

    Between 1992 and 1996, 31 cases (8 men and 23 women) with primary hyperparathyroidism (PHPT) were treated in our department. In this study, we compared which of the preoperative localization methods was most useful in the detection of PHPT. The sensitivity for detection of abnormal parathyroid glands was 88.6% on ultrasonography (US), 76.9% on magnetic resonance imaging (MRI), 74.3% on Tl-Tc subtraction scintigraphy and 68.8% on computed tomography. We concluded that US should be performed first, with MRI as a supplementary method, for the detection of abnormal parathyroid glands and the evaluation of invasion within the body. (author)

  14. Preoperative Evaluation for Noncardiac Surgery.

    Science.gov (United States)

    Cohn, Steven L

    2016-12-06

    This issue provides a clinical overview of preoperative evaluation for noncardiac surgery, focusing on risk factors, elements of evaluation, medication management, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  15. Duloxetine in OsteoArthritis (DOA) study : study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty

    NARCIS (Netherlands)

    Blikman, T.; Rienstra, W.; van Raaij, T. M.; ten Hagen, A. J.; Dijkstra, B.; Zijlstra, W. P.; Bulstra, S. K.; van den Akker-Scheek, I.; Stevens, M.

    2016-01-01

    Introduction Residual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degree

  16. Duloxetine in OsteoArthritis (DOA) study : study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty

    NARCIS (Netherlands)

    Blikman, T; Rienstra, W; van Raaij, T M; Ten Hagen, A J; Dijkstra, B; Zijlstra, W P; Bulstra, S K; van den Akker-Scheek, I; Stevens, M

    2016-01-01

    INTRODUCTION: Residual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degre

  17. Duloxetine in OsteoArthritis (DOA) study : study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty

    NARCIS (Netherlands)

    Blikman, T.; Rienstra, W.; van Raaij, T. M.; ten Hagen, A. J.; Dijkstra, B.; Zijlstra, W. P.; Bulstra, S. K.; van den Akker-Scheek, I.; Stevens, M.

    2016-01-01

    Introduction Residual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degree

  18. Chronic myeloid leukemia with pregnancy: Successful management of pregnancy and delivery with hydroxyurea and imatinib continued till delivery

    Directory of Open Access Journals (Sweden)

    Usha Yadav

    2013-01-01

    Full Text Available The concomitant occurrence of pregnancy and chronic myeloid leukemia is uncommon. We describe the successful management of a 30-year-old G3 P0, A2 woman who was diagnosed to have chronic myelogenous leukemia (CML in the third trimester of her pregnancy with intra-uterine growth retardation and oligohydroamnios. She was started on hydroxyurea and imatinib, and was continued till delivery and beyond. The use of imatinib did not have any adverse effects on the fetus, except for low birth weight and low APGAR at birth, but the later progress of the child was normal. We conclude that imatinib and hydroxyurea can be continued even at the third trimester in a pregnant lady with CML, if necessary.

  19. Chronic myeloid leukemia with pregnancy: Successful management of pregnancy and delivery with hydroxyurea and imatinib continued till delivery.

    Science.gov (United States)

    Yadav, Usha; Solanki, Sohan Lal; Yadav, Rupesh

    2013-01-01

    The concomitant occurrence of pregnancy and chronic myeloid leukemia is uncommon. We describe the successful management of a 30-year-old G3 P0, A2 woman who was diagnosed to have chronic myelogenous leukemia (CML) in the third trimester of her pregnancy with intra-uterine growth retardation and oligohydroamnios. She was started on hydroxyurea and imatinib, and was continued till delivery and beyond. The use of imatinib did not have any adverse effects on the fetus, except for low birth weight and low APGAR at birth, but the later progress of the child was normal. We conclude that imatinib and hydroxyurea can be continued even at the third trimester in a pregnant lady with CML, if necessary.

  20. Combination of Rapamycin and Imatinib in Treating Refractory Chronic Myeloid Leukemia Myeloid Blast Crisis: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Jing Xie; Xiang Zhang; Bao-zhi Fang; Guang-sheng He; Yun Zhao; De-pei Wu

    2013-01-01

    CHRONIC myeloid leukemia (CML) is character-ized by the presence of the BCR/ABL fusiongene, which is the resultof a reciprocal translo-cation betweenchromosomes 9 and 22, calledPhiladelphia (Ph) chromosome. Imatinib mesylate (imatinib), a specific small molecularinhibitor of BCR/ABL,couldimprove the prognosis of CML and is now the standard drugapplied in all phases of this disease.1 Despite the efficacy ofimatinib,the development of resistance and the persistence of minimal residual disease haveseriously impaired the efficiency of this medicine. Resistance may developthrough several differentmechanisms, such asmutations in the Abl kinase domain, BCR/ABL overexpression, or compensatory phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian targetof rapamycin (mTOR) activation.2,3Rapamycin, with mTOR asapotential therapeutic target, has been studied in patients with hematologic malignancies. Herewe report a case ofrefractory CML myeloid blast crisis successfully treated by the combination of rapamycin and imatinib.

  1. Preoperative fasting time in children.

    LENUS (Irish Health Repository)

    Adeel, S

    2012-02-01

    The aim of preoperative fasting is to prevent regurgitation and pulmonary aspiration while limiting potential problems of thirst, dehydration and hypoglycaemia. The American Society of Anaesthesiologists (ASA) has suggested guidelines for preoperative fasting for children undergoing elective surgery. We did a postal survey to determine the current practice regarding these guidelines amongst all specialist registrars in anaesthesia in Ireland. A questionnaire was sent to all specialist registrars in anaesthesia (90 in total), 60 (67%) were returned and analysed. The question asked was how long children should be kept fasting before elective surgery. The results of our survey suggest that most of the respondents are following the ASA guidelines for clear fluids and solids however there were differing opinion regarding the duration of fasting for formula milk and breast milk. In conclusion, we would recommend greater awareness and collaboration between anaesthetists, nurses and surgeons to ensure that fasting instructions are consistent with the ASA guidelines and that patient and their parents understand these directives as well.

  2. MDM2 promoter polymorphism and p53 codon 72 polymorphism in chronic myeloid leukemia: the association between MDM2 promoter genotype and disease susceptibility, age of onset, and blast-free survival in chronic phase patients receiving imatinib.

    Science.gov (United States)

    Liu, Yi-Chang; Hsiao, Hui-Hua; Yang, Wen-Chi; Liu, Ta-Chih; Chang, Chao-Sung; Yang, Ming-Yu; Lin, Pai-Mei; Hsu, Jui-Feng; Lee, Ching-Ping; Lin, Sheng-Fung

    2014-12-01

    The genetic or functional inactivation of the p53 pathway plays an important role with regards to disease progression from the chronic phase (CP) to blast phase (BP) and imatinib treatment response in chronic myeloid leukemia (CML). Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are associated with alternation of p53 activity, however the association regarding CML susceptibility and BP transformation under imatinib treatment is unclear. The MDM2 SNP309 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing from 116 CML patients, including 104 in the CP at diagnosis, and 162 healthy Taiwanese controls. The p53 R72P polymorphism was examined in all CML patients. The SNP309 G/G genotype was associated with an increased risk of CML susceptibility (OR: 1.82, 95% CI: 1.03-3.22, P = 0.037), and an earlier age of disease onset (log-rank P = 0.005) compared with the T/T + T/G genotypes. Higher MDM2 mRNA expression was found in G/G genotype compared with T/T (P = 0.034) and T/T + T/G (P = 0.056) genotypes. No associations were found between the p53 R72P genotypes and clinical parameters and survival outcomes. Among 62 CP patients receiving imatinib as first-line therapy, the G/G genotype was associated with a shorter blast-free survival (log-rank P = 0.048) and more clonal evolution compared with the T/T + T/G genotypes. In patients with advanced diseases at diagnosis, the G/G genotype was associated with a poor overall survival (log-rank P = 0.006). Closely monitoring CML patients harboring the G/G genotype and further large-scale studies are warranted.

  3. Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01–08)

    Science.gov (United States)

    Wen, Patrick Y.; Yung, W.K. Alfred; Lamborn, Kathleen R.; Norden, Andrew D.; Cloughesy, Timothy F.; Abrey, Lauren E.; Fine, Howard A.; Chang, Susan M.; Robins, H. Ian; Fink, Karen; DeAngelis, Lisa M.; Mehta, Minesh; Di Tomaso, Emmanuelle; Drappatz, Jan; Kesari, Santosh; Ligon, Keith L.; Aldape, Ken; Jain, Rakesh K.; Stiles, Charles D.; Egorin, Merrill J.; Prados, Michael D.

    2009-01-01

    Platelet-derived growth factor (PDGF) and its receptors (PDGFR) are frequently coexpressed in meningiomas, potentially contributing to their pathogenesis. The North American Brain Tumor Consortium conducted a phase II study to evaluate the therapeutic potential of imatinib mesylate (Gleevec), a PDGFR inhibitor, in patients with recurrent meningiomas. Patients were stratified into benign (WHO grade I) meningiomas or atypical (WHO grade II) and malignant (WHO grade III) meningiomas. The primary end point was 6-month progression-free survival (6M-PFS). Patients requiring enzyme-inducing antiepileptic drugs were ineligible. Patients received imatinib at a dose of 600 mg/day for the first 4-week cycle and then gradually increased to 800 mg/day for subsequent cycles, if there were no unacceptable toxicities. Plasma concentrations of imatinib and its active metabolite, CGP74588, were assessed. Twenty-three heavily pre-treated patients were enrolled into the study (13 benign, 5 atypical, and 5 malignant meningiomas), of whom 22 were eligible. The study was closed prematurely due to slow accrual. Tissue was available only from a minority of patients, but in these specimens there was uniform distribution of PDGFR, the drug target. Imatinib was generally well tolerated. Of 19 patients evaluable for response, 10 progressed at the first scan, and 9 were stable. There were no complete or partial responses. Overall median PFS was 2 months (range, 0.7–34 months); 6M-PFS was 29.4%. For benign meningiomas, median PFS was 3 months (range, 1.1–34 months); 6M-PFS was 45%. For atypical and malignant meningiomas, median PFS was 2 months (range, 0.7–3.7 months); 6M-PFS was 0%. Cycle 1 trough concentrations of imatinib and CGP74588 were 2,129 ± 1,600 ng/ml and 517 ± 326 ng/ml, respectively. Single-agent imatinib was well tolerated but had no significant activity in recurrent meningiomas. Trough plasma concentrations of imatinib exceeded those associated with imatinib activity in

  4. Preoperative information management system using wireless PDAs.

    Science.gov (United States)

    Sawa, Tomohiro; Okahara, Masaharu; Santo, Masayuki; Schmidt, Ulrich; Nakata, Yoshinori; Morita, Shigeho; Ohno-Machado, Lucila

    2003-01-01

    Personal Digital Assistant (PDA) and wireless communication are currently available in clinical settings. We developed wireless PDA software that assists anesthesiologists in pre-operative patient assessment. The device communicates with the hospital information system through a wireless LAN and is equipped with pre-programmed data entry templates for pre-operative assessment. As a preliminary test of the device, we randomly assigned residents in preoperative assessment to an intervention and a control arm and compared the results.

  5. Preoperative antibiotics for septic arthritis in children: delay in diagnosis.

    Science.gov (United States)

    MacLean, Simon B M; Timmis, Christopher; Evans, Scott; Lawniczak, Dominik; Nijran, Amit; Bache, Edward

    2015-04-01

    To review the records of 50 children who underwent open joint washout for septic arthritis with (n=25) or without (n=25) preoperative antibiotics. Records of 50 children who underwent open joint washout for presumed septic arthritis with (n=25) or without (n=25) preoperative antibiotics were reviewed. 17 boys and 8 girls aged 3 weeks to 16 years (median, 1.5 years) who were prescribed preoperative antibiotics before joint washout were compared with 12 boys and 13 girls aged one month to 14 years (median, 2 years) who were not. Following arthrotomy and washout, all patients were commenced on high-dose intravenous antibiotics. Patients were followed up for 6 to 18 months until asymptomatic. Patients who were referred from places other than our emergency department were twice as likely to have been prescribed preoperative antibiotics (p=0.0032). Patients prescribed preoperative antibiotics had a longer median (range) time from symptom onset to joint washout (8 [2-23] vs. 4 [1-29] days, p=0.05) and a higher mean erythrocyte sedimentation rate (93.1 vs. 54.3 mm/h, p=0.023) at presentation. Nonetheless, the 2 groups were comparable for weight bearing status, fever, and positive culture, as well as the mean (range) duration of antibiotic treatment (4.9 [4-7] vs. 4.7 [1-8] weeks, p=0.586). Preoperative antibiotics should be avoided in the management of septic arthritis in children. Their prescription delays diagnosis and definitive surgery, and leads to additional washouts and complications. A high index of suspicion and expedite referral to a specialist paediatric orthopaedic unit is needed if septic arthritis is suspected.

  6. Trends in the treatment changes and medication persistence of chronic myeloid leukemia in Taiwan from 1997 to 2007: a longitudinal population database analysis

    Directory of Open Access Journals (Sweden)

    Chang Chao-Sung

    2012-10-01

    Full Text Available Abstract Background Few studies have examined the longitudinal changes in the patterns, selection, and utilization of treatments for chronic myeloid leukemia (CML in routine clinical practice since the introduction of imatinib. Therefore, we investigated the trends in CML therapy, including changes, patterns, and persistence to imatinib therapy among patients with newly diagnosed CML. Methods We conducted a cross-sectional and longitudinal analysis of 11 years of claims data for patients with newly diagnosed CML included in the Taiwan National Health Insurance program. Pharmacy and diagnosis claims for newly diagnosed CML recorded between 1997 and 2007 year were extracted from the database. Annual overall use, new use of CML therapy, and persistence to imatinib therapy were estimated. The Anatomical Therapeutic Chemical codes for CML therapy [i.e., imatinib and conventional therapy: busulfan, hydroxyurea, interferon-α (IFNα, and cytarabine], and the process code for hematopoietic stem cell transplantation were used to categorize treatment patterns. Associations with patients characteristics were analyzed by multivariate logistic regression. Results Overall, the proportion of patients with newly diagnosed CML to all patients with CML increased by approximately 4-fold between 1998 and 2007. There were steady increases in the proportions of all treated patients and those starting therapy from 2003 to 2007. Fewer comorbid conditions and lower severity of CML were associated with treatment initiation. Medication persistence varied according to treatment duration, as 38.7% patients continued imatinib for ≥ 18 months without interruption but only 7.7% continued imatinib for ≥ 5 years. Factors associated with persistence to imatinib therapy were removal of the need for prior authorization for imatinib, and prior use of hydroxyurea and IFNα, whereas having undergone hematopoietic stem cell transplantation led to reduced likelihood

  7. Decreased therapeutic effects of noscapine combined with imatinib mesylate on human glioblastoma in vitro and the effect of midkine

    Directory of Open Access Journals (Sweden)

    Aktas Esin

    2011-06-01

    Full Text Available Abstract Background Glioblastoma (GBM develops resistance to the advances in chemotherapy leading to poor prognosis and life quality. Consequently, new treatment modalities are needed. Our aims were to investigate the effects of combined noscapine (NOS and imatinib mesylate (IM on human GBM in vitro and the role of midkine (MK in this new combination treatment. Methods Monolayer and spheroid cultures of T98G human GBM cell line were used to evaluate the effects of IM (10 μM, Nos (10 μM and their combination on cell proliferation and apoptotic indexes, cell cycle, the levels of antiapoptotic MK, MRP-1, p170, PFGFR-α, EGFR, bcl-2 proteins, apoptotic caspase-3 levels, morphology (SEM and ultrastructure (TEM for 72 hrs. Results were statistically analyzed using the Student's t-test. Results The combination group induced highest decrease in cell proliferation and apoptotic indexes, caspase-3 levels, MRP-1 and PDGFR-α levels. The decrease in p170 levels were lower than IM but higher that NOS. The highest increases were in EGFR, MK, bcl-2 and cAMP levels in the combination group. The G0+G1 cell cycle arrest at the end of 72nd hr was the lowest in the combination group. Apoptotic appearence was observed rarely both in the morphologic and ultrastructural evaluation of the combination group. In addition, autophagic vacuoles which were frequently observed in the IM group were observed rarely. Conclusions The combination of Nos with IM showed antagonist effect in T98G human GBM cells in vitro. This antagonist effect was correlated highly with MK levels. The effects of NOS on MRP-1, MK and receptor tyrosine kinase levels were firstly demonstrated in our report. In addition, we proposed that MK is one of the modulator in the switch of autophagy to cell death or survival/resistance.

  8. Preoperative anemia in colon cancer: assessment of risk factors.

    Science.gov (United States)

    Dunne, James R; Gannon, Christopher J; Osborn, Tiffany M; Taylor, Michelle D; Malone, Debra L; Napolitano, Lena M

    2002-06-01

    Anemia is common in cancer patients and is associated with reduced survival. Recent studies document that treatment of anemia with blood transfusion in cancer patients is associated with increased infection risk, tumor recurrence, and mortality. We therefore investigated the incidence of preoperative anemia in colorectal cancer and assessed risk factors for anemia. Prospective data were collected on 311 patients diagnosed with colorectal cancer over a 6-year period from 1994 through 1999. Patients were stratified by age, gender, presenting complaint, preoperative hematocrit, American Joint Committee on Cancer (AJCC) stage, and TNM classification. Discrete variables were compared using Pearson's Chi-square analysis. Continuous variables were compared using Student's t test. Differences were considered significant when P colon cancer with an incidence of 57.6 per cent followed by left colon cancer (42.2%) and rectal cancer (29.8%). Patients with right colon cancer had significantly lower preoperative hematocrits compared with left colon cancer (33 +/- 8.5 vs 36 +/- 7.4; P rectal cancer (33 +/- 8.5 vs 38 +/- 6.0; P colon cancer also had significantly increased stage at presentation compared with left colon cancer (2.3 +/- 1.3 vs 2.1 +/- 1.2; P cancer. We conclude that there is a high incidence of anemia in patients with colon cancer. Patients with right colon cancer had significantly lower preoperative hematocrits and higher stage of cancer at diagnosis. Complete colon evaluation with colonoscopy is warranted in patients with anemia to improve earlier diagnosis of right colon cancer. A clinical trial of preoperative treatment of anemic colorectal cancer patients with recombinant human erythropoietin is warranted.

  9. UV Differentially Induces Oxidative Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and Resistant to Imatinib

    Directory of Open Access Journals (Sweden)

    Ewelina Synowiec

    2015-08-01

    Full Text Available Chronic myeloid leukemia (CML cells express the active BCR-ABL1 protein, which has been targeted by imatinib in CML therapy, but resistance to this drug is an emerging problem. BCR-ABL1 induces endogenous oxidative stress promoting genomic instability and imatinib resistance. In the present work, we investigated the extent of oxidative stress, DNA damage, apoptosis and expression of apoptosis-related genes in BCR-ABL1 cells sensitive and resistant to imatinib. The resistance resulted either from the Y253H mutation in the BCR-ABL1 gene or incubation in increasing concentrations of imatinib (AR. UV irradiation at a dose rate of 0.12 J/(m2·s induced more DNA damage detected by the T4 pyrimidine dimers glycosylase and hOGG1, recognizing oxidative modifications to DNA bases in imatinib-resistant than -sensitive cells. The resistant cells displayed also higher susceptibility to UV-induced apoptosis. These cells had lower native mitochondrial membrane potential than imatinib-sensitive cells, but UV-irradiation reversed that relationship. We observed a significant lowering of the expression of the succinate dehydrogenase (SDHB gene, encoding a component of the complex II of the mitochondrial respiratory chain, which is involved in apoptosis sensing. Although detailed mechanism of imatinib resistance in AR cells in unknown, we detected the presence of the Y253H mutation in a fraction of these cells. In conclusion, imatinib-resistant cells may display a different extent of genome instability than their imatinib-sensitive counterparts, which may follow their different reactions to both endogenous and exogenous DNA-damaging factors, including DNA repair and apoptosis.

  10. Preoperative Smoking Status and Postoperative Complications

    DEFF Research Database (Denmark)

    Grønkjær, Marie; Eliasen, Marie; Skov-Ettrup, Lise Skrubbeltrang;

    2014-01-01

    To systematically review and summarize the evidence of an association between preoperative smoking status and postoperative complications elaborated on complication type.......To systematically review and summarize the evidence of an association between preoperative smoking status and postoperative complications elaborated on complication type....

  11. A psychological preoperative program: effects on anxiety and cooperative behaviors.

    Science.gov (United States)

    Cuzzocrea, Francesca; Gugliandolo, Maria C; Larcan, Rosalba; Romeo, Carmelo; Turiaco, Nunzio; Dominici, Tiziana

    2013-02-01

    To evaluate the effectiveness of a psychological preoperative program in reducing preoperative anxiety and in promoting compliance of pediatric participants with surgical procedures. Fifty children and their mothers were subjected to two conditions of treatment to investigate whether psychological preparation activities and psychologist's support during all phases of the operatory iter (group 1) were as efficient in reducing mothers' and child's anxiety and in increasing the child's compliance as distraction activities (group 2). The observed child anxiety was assessed using mYPAS; compliant behaviors with Induction Compliance Checklist; and mothers' anxiety with Amsterdam Pre-operative Anxiety and Information Scale. Children of the first group were less anxious and more cooperative in the preoperative period and during anesthesia induction than in the other condition. The psychological program was also more efficient in reducing mothers' anxiety. Finally, the mothers of group 1 showed a significantly higher satisfaction and judged as significantly more effective the program proposed to prepare their children than the mothers of group 2. Preparing children through playful dramatization of the operative procedure, manipulation of medical instruments and psychologist's support may be useful in pediatric surgery structures. © 2013 Blackwell Publishing Ltd.

  12. Usefulness of preoperative MRI in recurrent anorectal fistula

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hwa Jin; Cho, Jae Ho; Kim, Jae Woon; Park, Bok Hwan; Hwang, Mi Soo; Sim, Min Chul; Byun, Woo Mok [Yeungnam Univ. School of Medicine, Daegu (Korea, Republic of)

    1997-04-01

    To evaluate the usefulness of preoperative MRI in the patient with recurrent anorectal fistula. Fourteen patients with recurrent anorectal fistula underwent non-contrast MRI. In eight patients, T1-, T2- and proton-weighted images were taken in the axial, coronal and sagittal planes, and T1- and T2-weighted images taken in the axial and coronal planes were obtained from the other six. Fourteen cases of anorectal fistula and eight cases in which there was a combined abscess were detected. Preoperative MRI clearly showed the exact anatomical relationship with the anal sphincter, levator ani and surrounding soft tissue. In two cases in which there was fibrous scarring of the fistula tract, low signal intensities were seen on all MRI sequences. Preoperative information in the group in which only axial and coronal T1- and T2-weighted images were obtained was sufficient. Preoperative MRI in patients with recurrent anorectal fistula or suspected multiple fistulous tracts provide objective information concerning the anatomical location and extension of a fistula and combined abscess and could thus reduce the reoperation rate. An understanding of pathologic state through MRI signal intensity can help decide the most appropriate course of treatment.

  13. Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Deenik, W.; van der Holt, B.; Verhoef, G.E.G.; Smit, W.M.; Kersten, M.J.; Kluin-Nelemans, Hanneke; Verdonck, L.F.; Ferrant, A.; Schattenberg, A.V.M.B.; Janssen, J.J.W.M.; Sonneveld, P.; Kooy, M.V.; Wittebol, S.; Willemze, R.; Wijermans, P.W.; Westveer, P.H.M.; Beverloo, H.B.; Valk, P.; Lowenberg, B.; Ossenkoppele, G.J.; Cornelissen, J.J.

    2008-01-01

    The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1-7) in conjunction with im

  14. Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia.

    Science.gov (United States)

    Deenik, Wendy; van der Holt, Bronno; Verhoef, Gregor E G; Smit, Willem M; Kersten, Marie J; Kluin-Nelemans, Hanneke C; Verdonck, Leo F; Ferrant, Augustin; Schattenberg, Anton V M B; Janssen, Jeroen J W M; Sonneveld, Pieter; van Marwijk Kooy, Marinus; Wittebol, Shulamit; Willemze, Roelof; Wijermans, Pierre W; Westveer, Petra H M; Beverloo, H Berna; Valk, Peter; Löwenberg, Bob; Ossenkoppele, Gert J; Cornelissen, Jan J

    2008-03-01

    The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1-7) in conjunction with imatinib (200 mg, 400 mg, 600 mg, or 800 mg), according to predefined, successive dose levels. All dose levels proved feasible. Seven dose-limiting toxicities (DLTs) were observed in 302 cycles of chemotherapy, which were caused by streptococcal bacteremia in 5 cases. Intermediate-dose cytarabine (1000 mg/m(2)) prolonged time to neutrophil recovery and platelet recovery compared with a standard dose (200 mg/m(2)). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery compared with a standard dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3 or 4 were observed after intermediate-dose cytarabine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete cytogenetic response in 48% and a major molecular response in 30% of patients, which increased to 46% major molecular responses at 1 year, including 13% complete molecular responses. We conclude that combination therapy of escalating dosages of imatinib and cytarabine is feasible. This study was registered at www.kankerbestrijding.nl as no. CKTO-2001-03.

  15. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study.

    Science.gov (United States)

    Ottmann, Oliver; Dombret, Hervé; Martinelli, Giovanni; Simonsson, Bengt; Guilhot, Francois; Larson, Richard A; Rege-Cambrin, Giovanna; Radich, Jerald; Hochhaus, Andreas; Apanovitch, Anne Marie; Gollerkeri, Ashwin; Coutre, Steven

    2007-10-01

    Patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015.

  16. Análise de pacientes com leucemia mieloide crônica com resistência primária ou secundária ao mesilato de imatinibe Analysis of chronic myelogenous leukemia patients with primary or secondary resistance to imatinib mesylate

    Directory of Open Access Journals (Sweden)

    Rita de Cássia S. Alves

    2009-01-01

    investigated in the Hematology and Hemotherapy Service of Santa Casa of Sao Paulo. The aim was to characterize the profile of resistance and study the presence of the mutation. The majority of resistant patients were in the most advanced phases of the disease. Risk factors for resistance in the chronic phase were a platelet count higher than 450,000/mm3 before imatinib treatment or less than 50,000/mm3 during treatment. The total hematological response rate and the time to achieve this were similar between resistant and non-resistant patients. Lower overall survival was observed with resistance. It was notable that ten resistant patients had complete cytogenetic responses after 12 months (late responses with both hematological and cytogenetic response rates similar to non-resistant patients (100%. Survival free from progression was similar up to 40 months and the overall survival rate was comparable up to 70 months. The overall survival and response to treatment were better than for the other resistant patients. In respect to the investigation of mutations, 22 resistant patients were investigated with eight presenting with the mutation (36.4% The presence of blast cells in the peripheral blood at diagnosis of patients in the chronic phase was characterized as a higher risk factor for this mutation.

  17. The study of resistant mechanisms and reversal in an imatinib resistant Ph+ acute lymphoblastic leukemia cell line.

    Science.gov (United States)

    Xing, Hongyun; Yang, Xi; Liu, Ting; Lin, Juan; Chen, Xiaoyi; Gong, Yuping

    2012-04-01

    In this study, we established an imatinib resistant Ph+ acute lymphoblastic leukemia (ALL) cell line SUP-B15/RI in vitro and studied the mechanism of imatinib resistance. Our results showed that the BCR-ABL1 fusion gene and the mdr1 gene were 6.1 times and 1.7 times, respectively, as high as that of parental SUP-B15 cell line. We found no mutation in the Abl kinase domain of SUP-B15/RI. Furthermore, the detection of cell signaling pathway of PI3K/AKT/mTOR, RAS/RAF, NF-κB, JNK and STAT showed the up-regulation of phosphorylation of AKT, mTOR, P70S6K, and RAF, ERK, and MEK, down-regulation of PTEN and 4EBP-1, and no change in other cell signaling pathways in SUP-B15/RI. However, dasatinib and nilotinib showed partial resistance. Interestingly, bortezomib had no resistance. Imatinib combination with rapamycin had synergistic effect on overcoming the resistance. Altogether, over-expression of BCR-ABL1 and mdr1 gene were involved in the resistance mechanisms, and up-regulation of the cell signaling pathways of PI3K/AKT/mTOR, RAS/RAF in SUP-B15/RI cell line may be correlated with them. The SUP-B15/RI cell line was also resistant to the second generation tyrosine kinase, dasatinib, and nilotinib, not bortezomib. The combination of imatinib with rapamycin can partially overcome the resistance and blockade of the ubiquitin-proteasome can be also a promising pathway to overcome imatinib resistance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Increased peroxisome proliferator-activated receptor-gamma activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells.

    Science.gov (United States)

    Wang, Jueqiong; Lu, Liu; Kok, Chung H; Saunders, Verity A; Goyne, Jarrad M; Dang, Phuong; Leclercq, Tamara M; Hughes, Timothy P; White, Deborah L

    2017-02-02

    Imatinib is actively transported by OCT-1 influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Here we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor gamma agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor gamma antagonists (GW9662, T0070907) increase OCT-1 activity. Importantly, these effects can lead to corresponding changes in sensitivity to Bcr-Abl kinase inhibition. Results were confirmed in peroxisome proliferator-activated receptor gamma-transduced K562 cells. Furthermore, we identified a strong negative correlation between OCT-1 activity and peroxisome proliferator-activated receptor gamma transcriptional activity in diagnostic chronic myeloid leukemia patients (n=84; preceptor gamma activation has a negative impact on the intracellular uptake of imatinib and consequent Bcr-Abl kinase inhibition. The inter-patient variability of peroxisome proliferator-activated receptor gamma activation likely accounts for the heterogeneity observed in patient OCT-1 activity at diagnosis. Recently, the peroxisome proliferator-activated receptor gamma agonist pioglitazone was reported to act synergistically with imatinib targeting the residual chronic myeloid leukemia stem cell pool. Our findings suggest that peroxisome proliferator-activated receptor gamma ligands have differential effects on circulating mononuclear cells compared to stem cells. Since the effect of peroxisome proliferator-activated receptor gamma activation on imatinib uptake in mononuclear cells may counteract the clinical benefit of this activation in stem cells, caution should be applied when combining these therapies, especially in patients with high peroxisome proliferator-activated receptor gamma

  19. [Evaluation of preoperative anxiety in patients requiring glaucoma filtration surgery].

    Science.gov (United States)

    Lemaitre, S; Blumen-Ohana, E; Akesbi, J; Laplace, O; Nordmann, J-P

    2014-01-01

    Preoperative anxiety is often expressed by patients requiring filtration surgery for their glaucoma. So far, there has been no scale for screening this group of patients for preoperative anxiety. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) is a self-evaluation questionnaire which has been used in specialties other than ophthalmology and which makes it possible to identify the adult patients with a high level of preoperative anxiety over an upcoming surgical procedure. The purpose of this study is to estimate the preoperative anxiety in glaucoma patients requiring filtration surgery. We performed a prospective study of 36 adult patients with chronic glaucoma not responding to medical treatment and who were about to undergo filtration surgery (trabeculectomy or deep sclerectomy). The APAIS questionnaire was given to the patients after discussing the indication for surgery. A global anxiety score (ranging from 4 to 20) above 10 defined patients with a high level of preoperative anxiety. We attempted to identify among these patients the factors related to filtration surgery which caused them anxiety (lack of control of intraocular pressure, risk of blindness, presence of the filtering bleb). In our sample of patients, we found that glaucoma was a source of anxiety. That was also true for the surgical procedure, though most patients believe that once the decision had been made, their psychological status was not modified by the upcoming procedure. The patient-clinician relationship is important in any chronic disease, all the more so in glaucoma, since this disease remains asymptomatic for a long time. When filtration surgery is necessary, the patients are going to express less preoperative anxiety if they trust their physician and if individualized information has been given to them The French version of the APAIS is a quick scale, easily completed, that can be recommended for evaluating anxiety and patients' need for information prior to filtering

  20. 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

  1. Field-assisted paper spray mass spectrometry for the quantitative evaluation of imatinib levels in plasma.

    Science.gov (United States)

    D'Aronco, Sara; Calandra, Eleonora; Crotti, Sara; Toffoli, Giuseppe; Marangon, Elena; Posocco, Bianca; Traldi, Pietro; Agostini, Marco

    Drug levels in patients' bloodstreams vary among individuals and consequently therapeutic drug monitoring (TDM) is fundamental to controlling the effective therapeutic range. For TDM purposes, different analytical approaches have been used, mainly based on immunoassay, liquid chromatography- ultraviolet, liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. More recently a matrix-assisted laser desorption/ionisation method has been proposed for the determination of irinotecan levels in the plasma of subjects under therapy and this method has been cross- validated by comparison with data achieved by LC-MS/MS. However, to reach an effective point-of-care monitoring of plasma drug concentrations, a TDM platform technology for fast, accurate, low-cost assays is required. In this frame, recently the use of paper spray mass spectrometry, which is becoming a popular and widely employed MS method, has been proposed. In this paper we report the results obtained by the development of a paper spray-based method for quantitative analysis in plasma samples of imatinib, a new generation of anticancer drug. Preliminary experiments showed that poor sensitivity, reproducibility and linear response were obtained by the "classical" paper spray set-up. In order to achieve better results, it was thought of interest to operate in presence of a higher and more homogeneous electrical field. For this aim, a stainless steel needle connected with the high voltage power supply was mounted below the paper triangle. Furthermore, in order to obtain valid quantitative data, we analysed the role of the different equilibria participating to the phenomena occurring in paper spray experiments, depending either on instrumental parameters or on the chemical nature of analyte and solvents. A calibration curve was obtained by spiking plasma samples containing different amounts of imatinib (1) with known amounts of deuterated imatinib (1d3) as

  2. Preoperative optimization of the vascular surgery patient

    Directory of Open Access Journals (Sweden)

    Zhan HT

    2015-07-01

    Full Text Available Henry T Zhan,1 Seth T Purcell,1,2 Ruth L Bush1 1Texas A&M Health Science Center College of Medicine, Bryan, 2Baylor Scott and White, Temple, TX, USA Abstract: It is well known that patients who suffer from peripheral (noncardiac vascular disease often have coexisting atherosclerotic diseases of the heart. This may leave the patients susceptible to major adverse cardiac events, including death, myocardial infarction, unstable angina, and pulmonary edema, during the perioperative time period, in addition to the many other complications they may sustain as they undergo vascular surgery procedures, regardless of whether the procedure is performed as an open or endovascular modality. As these patients are at particularly high risk, up to 16% in published studies, for postoperative cardiac complications, many proposals and algorithms for perioperative optimization have been suggested and studied in the literature. Moreover, in patients with recent coronary stents, the risk of noncardiac surgery on adverse cardiac events is incremental in the first 6 months following stent implantation. Just as postoperative management of patients is vital to the outcome of a patient, preoperative assessment and optimization may reduce, and possibly completely alleviate, the risks of major postoperative complications, as well as assist in the decision-making process regarding the appropriate surgical and anesthetic management. This review article addresses several tools and therapies that treating physicians may employ to medically optimize a patient before they undergo noncardiac vascular surgery. Keywords: perioperative care, intraoperative care, medical management, risk evaluation/stratification, medical treatment

  3. A fresh look at preoperative body washing

    Science.gov (United States)

    Tanner, Judith; Gould, Dinah; Jenkins, Philip; Hilliam, Rachel; Mistry, Neetesh; Walsh, Susannah

    2012-01-01

    National guidelines do not support preoperative body washing to reduce surgical site infections, instead recommending bathing or showering with soap. Yet preoperative body washing continues to be widely used in many hospitals across Europe. This paper suggests that existing trials of preoperative body washing, upon which guidelines are based, are dated and proposes a new investigation of preoperative body washing using modern definitions of surgical site infection with standardised patient follow up, modern surgical techniques and well designed trials. This paper provides a critique of existing guidelines and describes a randomised trial with 60 participants to compare the effect of soap and two antiseptic washing products on colony forming units (CFUs) for up to six hours. Chlorhexidine gluconate and octenidine were significantly more effective than soap in reducing CFUs in the underarm, and chlorhexidine was significantly more effective than soap in reducing CFUs in the groin. PMID:22448182

  4. Preoperative steroid in abdominal wall reconstruction

    DEFF Research Database (Denmark)

    Jensen, Kristian Kiim; Brøndum, Tina Lee; Belhage, Bo

    2016-01-01

    INTRODUCTION: Preoperative administration of high-dose glucocorticoid leads to improved recovery and decreased length of stay after abdominal surgery. Even so, studies on administration of glucocorticoids for patients undergoing abdominal wall reconstruction (AWR) for giant ventral hernia repair ...

  5. Preoperative alcohol cessation prior to elective surgery

    DEFF Research Database (Denmark)

    Oppedal, Kristian; Møller, Ann Merete; Pedersen, Bolette

    2012-01-01

    Hazardous drinking has been associated with an increased postoperative complication rate after surgery. Common complications include postoperative infections, cardiopulmonary complications, and bleeding episodes. Preoperative abstinence may to some degree reverse alcohol-induced pathophysiological...

  6. Preoperative steroid in abdominal wall reconstruction

    DEFF Research Database (Denmark)

    Jensen, Kristian Kiim; Brøndum, Tina Lee; Belhage, Bo;

    2016-01-01

    INTRODUCTION: Preoperative administration of high-dose glucocorticoid leads to improved recovery and decreased length of stay after abdominal surgery. Even so, studies on administration of glucocorticoids for patients undergoing abdominal wall reconstruction (AWR) for giant ventral hernia repair ...

  7. [Induction of hospital indebtedness due to medicine purchases under monopoly conditions: the case of imatinib mesylate].

    Science.gov (United States)

    Scopel, Carolinne Thays; Chaves, Gabriela Costa

    2015-03-01

    Medicine expenditures consume a large share of the health budget, so knowledge on the use of these funds is essential for decision-making in public health and improvement of pharmaceutical care. This study analyzed the indebtedness of a high-complexity university hospital due to increased spending on imatinib mesylate. The descriptive study was based on analysis of documents and records in the Hospital Information System (SIH) from 2002 to 2010. Starting with inclusion of the medicine in the budget, the study mapped strategies by the pharmaceutical industry and government, as well as government responses to reduce the product's price. The systematization and publication of information stored in files and electronic databases can help monitor the results of programs funded by the Brazilian Ministry of Health.

  8. [A Case of Resected Giant Gastrointestinal Stromal Tumor Associated with Intraperitoneal Bleeding Following Imatinib Administration].

    Science.gov (United States)

    Ide, Ryuta; Suzuki, Takahisa; Takakura, Yuji; Oshita, Akihiko; Ikeda, Satoshi; Matsugu, Yasuhiro; Nakahara, Hideki; Urushihara, Takashi; Itamoto, Toshiyuki; Shinozaki, Katsunori

    2016-09-01

    A 76-year-old woman with tarry stool was referred to our hospital for further examination. Contrast-enhanced computed tomography(CT)revealed a heterogeneous 15 cm tumor located in the left upper abdominal cavity. The tumor had a rich vascularity and was associated with intra-abdominal bleeding. Gastroscopy showed a large submucosal tumor in the gastric body. A biopsy was performed, and the patient was diagnosed with a c-kit-positive gastrointestinal stromal tumor(GIST)of the stomach. Imatinib mesylate(400mg/day)was administered for 6 months. Vascularity in the tumor was diminished and no new lesion had emerged, although there was no remarkable reduction in tumor size. The patient underwent partial gastrectomy and splenectomy with curative intent. She is currently alive 1 year and 4 months after surgery with no evidence of recurrence.

  9. Elimination and Recycling of Imatinib by Ethoxylated Multi-Walled Carbon Nanotubes from aqueous solutions

    Directory of Open Access Journals (Sweden)

    Maryam Pakzad Masouleh

    2015-06-01

    Full Text Available An adsorbent and carrier based on ethoxylated functionalized multi-walled carbon nanotubes (f-MWCNTs were prepared with diethylene glycol (2EG followed by esterification process. Resultant dietylene glycolated MWCNTs (MWCNTs-2EG used for elimination of Imatinib mesylate (Ima from water. Maximum Ima adsorption per 3 mg of adsorbent and 9 mg of initial Ima was 8.76 mg. maximum recycling at two pH values 7.4 and 5.3 was determined about 6.15 mg (70% and 7.42 mg (85% respectively. Ima elimination and recycling process is greatly enhanced by the creation of functional groups on the MWCNTs-2EG in compare with carboxylated MWCNTs (MWCNTs-COOH.

  10. Preoperative education for lumbar surgery for radiculopathy

    OpenAIRE

    Louw, A; Louw, Q; L. Crous

    2009-01-01

    To date no studies have been published on preoperative education forpatients who had lumbar surgery. The aim of this study was to determine if there is a demand for preoperative education for patients who had lumbar surgery for radiculopathy. A convenience sample of 47 patients who had lumbar surgery and a random sample of 141 physiotherapists involved in treating patients who had lumbar surgery completed a newly developed spinal surgery questionnaire. The data were analyzed using descriptive...

  11. Preoperative prediction of severe postoperative pain.

    Science.gov (United States)

    Kalkman, C J; Visser, K; Moen, J; Bonsel, G J; Grobbee, D E; Moons, K G M

    2003-10-01

    We developed and validated a prediction rule for the occurrence of early postoperative severe pain in surgical inpatients, using predictors that can be easily documented in a preoperative setting. A cohort of surgical inpatients (n=1416) undergoing various procedures except cardiac surgery and intracranial neurosurgery in a University Hospital were studied. Preoperatively the following predictors were collected: age, gender, type of scheduled surgery, expected incision size, blood pressure, heart rate, Quetelet index, the presence and severity of preoperative pain, health-related quality of life the (SF-36), Spielberger's State-Trait Anxiety Inventory (STAI) and the Amsterdam Preoperative Anxiety and Information Scale (APAIS). The outcome was the presence of severe postoperative pain (defined as Numeric Rating Scale > or =8) within the first hour postoperatively. Multivariate logistic regression in combination with bootstrapping techniques (as a method for internal validation) was used to derive a stable prediction model. Independent predictors of severe postoperative pain were younger age, female gender, level of preoperative pain, incision size and type of surgery. The area under the receiver operator characteristic (ROC) curve was 0.71 (95% CI: 0.68-0.74). Adding APAIS scores (measures of preoperative anxiety and need for information), but not STAI, provided a slightly better model (ROC area 0.73). The reliability of this extended model was good (Hosmer and Lemeshow test p-value 0.78). We have demonstrated that severe postoperative pain early after awakening from general anesthesia can be predicted with a scoring rule, using a small set of variables that can be easily obtained from all patients at the preoperative visit. Before this internally validated preoperative prediction rule can be applied in clinical practice to support anticipatory pain management, external validation in other clinical settings is necessary.

  12. Preoperative pulmonary rehabilitation in lung cancer patients undergoing lung resection surgery

    OpenAIRE

    Sebio García, Raquel

    2016-01-01

    [Abstract] INTRODUCTION: Lung resection surgery (LRS) remains the treatment of choice for early stages of lung cancer but significant morbidity is associated, especially among patients with poor preoperative status. Preoperative exercise training (PET) has been proposed as an effective way of optimizing patients’ condition before surgery and enhancing postoperative recovery. However, it remains unknown whether or not similar results can be achieved after video-assisted thora...

  13. Preoperative pulmonary rehabilitation in lung cancer patients undergoing lung resection surgery

    OpenAIRE

    Sebio García, Raquel

    2016-01-01

    [Abstract] INTRODUCTION: Lung resection surgery (LRS) remains the treatment of choice for early stages of lung cancer but significant morbidity is associated, especially among patients with poor preoperative status. Preoperative exercise training (PET) has been proposed as an effective way of optimizing patients’ condition before surgery and enhancing postoperative recovery. However, it remains unknown whether or not similar results can be achieved after video-assisted thora...

  14. Assessment of preoperative ultrasonography of the neck and elective neck dissection in patients with oral squamous cell carcinoma.

    NARCIS (Netherlands)

    Wensing, B.M.; Merkx, M.A.W.; Wilde, P.C.M. de; Marres, H.A.M.; Hoogen, F.J.A. van den

    2010-01-01

    Estimating the value of our preoperative workup in the treatment of patients with clinically N0 (cN0) squamous cell carcinoma of the oral cavity. Retrospective analysis. Results of preoperative palpation, ultrasound (US) and ultrasound-guided fine needle aspiration cytology (FNAC) were compared to t

  15. Imatinib atenua a fibrose miocárdica em associação com a inibição da atividade do PDGFRα Imatinib attenuates myocardial fibrosis in association with inhibition of the PDGFRα activity

    Directory of Open Access Journals (Sweden)

    Li-kun Ma

    2012-01-01

    Full Text Available FUNDAMENTO: O Imatinib é um inibidor do receptor tirosina-quinase que foi confirmada como exercendo um efeito inibidor sobre a atividade do receptor do PDGF, fator de crescimento plaquetário (PDGFRα e PDGFRβ. OBJETIVO: Investigar o efeito protetor do Imatinib na fibrose miocárdica em acetato de deoxicorticosterona (DOCA/ratos com hipertensão induzida por sal. MÉTODOS: Sessenta ratos Sprague-Dawley machos, uninefrectomizados foram distribuídos em três grupos: ratos controles (grupo CON: grupo deoxicorticosterona (grupo DOCA; grupo deoxicorticosterona e Imatinib (grupo DOCA IMA. A Pressão Arterial Sistólica (PAS foi medida quinzenalmente. Foi estudada a porção apical do ventrículo esquerdo. Foram empregados: coloração vermelho sirius, coloração de hematoxilina-eosina, imuno-histoquímica e ensaio de western blot. RESULTADOS: A PAS nos grupos DOCA e IMA+DOCA foi maior que no grupo CON nos dias 14 e 28. Os animais do grupo DOCA apresentaram fibrose intersticial e perivascular grave no dia 28, e as expressões de PI, PIII, tenascina-C e fibronectina foram significativamente maiores que nos grupos DOCA+IMA e CON. Quando comparados com o grupo CON, os grupos DOCA e DOCA+IMA apresentaram resposta inflamatória de tecido miocárdico e infiltração de monócitos/macrófagos de diferentes graus. As expressões proteicas do PDGF-A, PDGF-C e PDGFRα foram significativamente maiores nos grupos DOCA e DOCA+IMA que no grupo CON, mas a expressão proteica do p-PDGFRα no grupo DOCA+IMA foi menor que no DOCA. CONCLUSÃO: O Imatinib pode exercer efeitos inibitórios sobre a fibrose miocárdica em ratos com hipertensão induzida por DOCA/sal, os quais podem ser atribuídos à inibição da atividade do PDGFR-α.BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ activity. OBJECTIVE: To investigate the protective

  16. Imatinib atenua a fibrose miocárdica em associação com a inibição da atividade do PDGFRα Imatinib attenuates myocardial fibrosis in association with inhibition of the PDGFRα activity

    Directory of Open Access Journals (Sweden)

    Li-kun Ma

    2012-12-01

    Full Text Available FUNDAMENTO: O Imatinib é um inibidor do receptor tirosina-quinase que foi confirmada como exercendo um efeito inibidor sobre a atividade do receptor do PDGF, fator de crescimento plaquetário (PDGFRα e PDGFRβ. OBJETIVO: Investigar o efeito protetor do Imatinib na fibrose miocárdica em acetato de deoxicorticosterona (DOCA/ratos com hipertensão induzida por sal. MÉTODOS: Sessenta ratos Sprague-Dawley machos, uninefrectomizados foram distribuídos em três grupos: ratos controles (grupo CON: grupo deoxicorticosterona (grupo DOCA; grupo deoxicorticosterona e Imatinib (grupo DOCA IMA. A Pressão Arterial Sistólica (PAS foi medida quinzenalmente. Foi estudada a porção apical do ventrículo esquerdo. Foram empregados: coloração vermelho sirius, coloração de hematoxilina-eosina, imuno-histoquímica e ensaio de western blot. RESULTADOS: A PAS nos grupos DOCA e IMA+DOCA foi maior que no grupo CON nos dias 14 e 28. Os animais do grupo DOCA apresentaram fibrose intersticial e perivascular grave no dia 28, e as expressões de PI, PIII, tenascina-C e fibronectina foram significativamente maiores que nos grupos DOCA+IMA e CON. Quando comparados com o grupo CON, os grupos DOCA e DOCA+IMA apresentaram resposta inflamatória de tecido miocárdico e infiltração de monócitos/macrófagos de diferentes graus. As expressões proteicas do PDGF-A, PDGF-C e PDGFRα foram significativamente maiores nos grupos DOCA e DOCA+IMA que no grupo CON, mas a expressão proteica do p-PDGFRα no grupo DOCA+IMA foi menor que no DOCA. CONCLUSÃO: O Imatinib pode exercer efeitos inibitórios sobre a fibrose miocárdica em ratos com hipertensão induzida por DOCA/sal, os quais podem ser atribuídos à inibição da atividade do PDGFR-α.BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ activity. OBJECTIVE: To investigate the protective

  17. Prevalence and factors associated with preoperative anxiety in children aged 5-12 years

    Directory of Open Access Journals (Sweden)

    Louise Amália de Moura

    2016-01-01

    Full Text Available Abstract Objective: to estimate the prevalence and factors associated with preoperative anxiety in children who wait for outpatient surgery. Method: cross-sectional analysis of baseline data of a prospective cohort study that investigates the predictors of postoperative pain in children aged 5-12 years submitted to inguinal and umbilical hernia repair. It was selected 210 children, which were interviewed in the preoperative holding area of a general hospital. Anxiety was evaluated using the modified Yale Preoperative Anxiety Scale (mYPAS. Sociodemographic and clinical variables were analyzed as exposure and anxiety (mYPAS final score>30 as outcome. Logistic regression was used to identify factors associated with preoperative anxiety. Results: forty-two percent (42.0% of children presented preoperative anxiety (CI95%: 35.7%-48.6%, with mean scores equal to 30.1 (SD=8.4. Factors associated with preoperative anxiety were: age group of 5-6 years (OR=2.28; p=0.007 and socioeconomic status classified as class C (OR=2.39; p=0.016. Conclusion: the evaluation of children who wait for outpatient surgery should be multidimensional and comprise information on age and socioeconomic status, in order to help in the identification and early treatment of preoperative anxiety.

  18. Prevalence and factors associated with preoperative anxiety in children aged 5-12 years 1

    Science.gov (United States)

    de Moura, Louise Amália; Dias, Iohanna Maria Guimarães; Pereira, Lilian Varanda

    2016-01-01

    Abstract Objective: to estimate the prevalence and factors associated with preoperative anxiety in children who wait for outpatient surgery. Method: cross-sectional analysis of baseline data of a prospective cohort study that investigates the predictors of postoperative pain in children aged 5-12 years submitted to inguinal and umbilical hernia repair. It was selected 210 children, which were interviewed in the preoperative holding area of a general hospital. Anxiety was evaluated using the modified Yale Preoperative Anxiety Scale (mYPAS). Sociodemographic and clinical variables were analyzed as exposure and anxiety (mYPAS final score>30) as outcome. Logistic regression was used to identify factors associated with preoperative anxiety. Results: forty-two percent (42.0%) of children presented preoperative anxiety (CI95%: 35.7%-48.6%), with mean scores equal to 30.1 (SD=8.4). Factors associated with preoperative anxiety were: age group of 5-6 years (OR=2.28; p=0.007) and socioeconomic status classified as class C (OR=2.39; p=0.016). Conclusion: the evaluation of children who wait for outpatient surgery should be multidimensional and comprise information on age and socioeconomic status, in order to help in the identification and early treatment of preoperative anxiety. PMID:27305179

  19. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, Oliver G; Wassmann, Barbara

    2005-01-01

    Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL) includes at least one-quarter of all adults with ALL. Until recently, conventional chemotherapy programs that have been effective in other precursor B-cell ALL cases have been unable to cure patients with this diagnosis. Allogeneic stem cell transplantation early in first remission has been the recommended therapy. The availability of imatinib mesylate and other tyrosine kinase inhibitors and small molecules that affect the BCR/ABL signaling pathways may be changing the treatment paradigm and the prognosis for these patients. The results from clinical trials using imatinib in the frontline setting and in relapsed patients as well as preliminary experience treating imatinib-resistant Ph(+) ALL will be described.

  20. Preoperative Chemoradiotheraph for Inflammatory Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Hongbo Ren; Qi Wang; Yaoxiong Yan; Shaolin Li; Biyou Huang

    2006-01-01

    OBJECTIVE To observe the effect of preoperative chemoradiotherapy for inflammatory breast cancer.METHODS From December 1996 to December 2000, we received and treated 21 patients with inflammatory breast carcinoma with a combinedmodality treatment. The chemotherapy protocol consisted of cyclophosphamide (CTX), pirarubicin (THP-ADM) and 5-fluorouracil (5-FU) or CTX, 5-Fu and methotrexate (MTX). The same infusion scheme was repeated on day 21. After 3~4 cycles the patients were treated with radiotherapy. When the radiation dose reached 40 Gy, the patients who were unable or unwilling to under go an operation received continued radiotherapy. When the radiation dose to the supra clavicular fossa and internal mammary lymph nodes reached 60 Gy and 50 Gy respectively, the radiotherapy was stopped. Chemotherapy was then continued with the original scheme. Patients who had indications for surgery and were willing to under go an operation received no treatment for 2 weeks, after which a total mastectomy was performed. Chemotherapy and radiotherapy was resumed with the original scheme after the operations. When the radiation dose reached 50 Gy, radiotherapy was stopped.RESULTS All patients were followed-up for more than 5 years with a follow-up rate of 100%. The overall 3 and 5-year survival rates of these patients were 42.9%, and 23.8% respectively. For patients in Stage ⅢB the 3 and 5-year survival rates were 50.0% and 27.8% respectively, and for patients in Stage Ⅳ, the 3 and 5-year survival rates were both 0.0%.There was a significant difference between the 2 stage groups (P<0.05,X2=11.60). For patients who received an operation, the 3 and 5-year survival rates were 80.0% and 33.3% respectively, For patients who were not treated with an operation, the 3 and 5-year survival rates were both0.0%, There was a significant difference between the operated and nonoperated groups (P<0.05, X2=11.64).CONCLUSION The prognosis of inflammatory breast carcinoma is poor

  1. Effectiveness of binaural beats in reducing preoperative dental anxiety.

    Science.gov (United States)

    Isik, B K; Esen, A; Büyükerkmen, B; Kilinç, A; Menziletoglu, D

    2017-07-01

    Binaural beats are an auditory illusion perceived when two different pure-tone sine waves are presented one to each ear at a steady intensity and frequency. We evaluated their effectiveness in reducing preoperative anxiety in dentistry. Sixty patients (30 in each group) who were to have impacted third molars removed were studied (experimental group: 20 women and 10 men, mean (range) age 24 (18-35) years, and control group: 22 women and 8 men, mean (range) age 28 (15-47) years). All patients were fully informed about the operation preoperatively, and their anxiety recorded on a visual analogue scale (VAS). The local anaesthetic was given and the patients waited for 10minutes, during which those in the experimental group were asked to listen to binaural beats through stereo earphones (200Hz for the left ear and 209.3Hz for the right ear). No special treatment was given to the control group. In both groups anxiety was then recorded again, and the tooth removed in the usual way. The paired t test and t test were used to assess the significance of differences between groups. The degree of anxiety in the control group was unchanged after the second measurement (p=0.625), while that in the experimental group showed a significant reduction in anxiety (p=0.001). We conclude that binaural beats may be useful in reducing preoperative anxiety in dentistry. Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Preoperative rectal cancer staging with phased-array MR

    Directory of Open Access Journals (Sweden)

    Giusti Sabina

    2012-03-01

    Full Text Available Abstract Background We retrospectively reviewed magnetic resonance (MR images of 96 patients with diagnosis of rectal cancer to evaluate tumour stage (T stage, involvement of mesorectal fascia (MRF, and nodal metastasis (N stage. Our gold standard was histopathology. Methods All studies were performed with 1.5-T MR system (Symphony; Siemens Medical System, Erlangen, Germany by using a phased-array coil. Our population was subdivided into two groups: the first one, formed by patients at T1-T2-T3, N0, M0 stage, whose underwent MR before surgery; the second group included patients at Tx N1 M0 and T3-T4 Nx M0 stage, whose underwent preoperative MR before neoadjuvant chemoradiation therapy and again 4-6 wks after the end of the treatment for the re-staging of disease. Our gold standard was histopathology. Results MR showed 81% overall agreement with histological findings for T and N stage prediction; for T stage, this rate increased up to 95% for pts of group I (48/96, while for group II (48/96 it decreased to 75%. Preoperative MR prediction of histologically involved MRF resulted very accurate (sensitivity 100%; specificity 100% also after chemoradiation (sensitivity 100%; specificity 67%. Conclusions Phased-array MRI was able to clearly estimate the entire mesorectal fat and surrounding pelvic structures resulting the ideal technique for local preoperative rectal cancer staging.

  3. Cardiopulmonary exercise testing (CPET) as preoperative test before lung resection.

    Science.gov (United States)

    Kallianos, Anastasios; Rapti, Aggeliki; Tsimpoukis, Sotirios; Charpidou, Andriani; Dannos, Ioannis; Kainis, Elias; Syrigos, Konstantinos

    2014-01-01

    Lung resection is still the only potentially curative therapy for patients with localized non-small lung cancer (NSCLC). However, the presence of cardiovascular comorbidities and underlying lung disease increases the risk of postoperative complications. Various studies have evaluated the use of different preoperative tests in order to identify patients with an increased risk for postoperative complications, associated with prolonged hospital stay and increased morbidity and mortality. In this topic review, we discuss the role of cardiopulmonary exercise testing (CPET) as one of the preoperative tests suggested for lung cancer patients scheduled for lung resection. We describe different types of exercise testing techniques and present algorithms of preoperative evaluation in lung cancer patients. Overall, patients with maximal oxygen consumption (VO2max) VO2max <15 mL/kg/min and both postoperative FEV1 and DLCO<40% predicted, are at high risk for perioperative death and postoperative cardiopulmonary complications, and thus should be offered an alternative medical treatment option. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Psychologists in preoperative programmes for children undergoing surgery.

    Science.gov (United States)

    Cuzzocrea, Francesca; Costa, Sebastiano; Gugliandolo, Maria Cristina; Larcan, Rosalba

    2016-06-01

    This study aimed to verify whether psychologists and game activities could reduce preoperative anxiety and promote compliance in paediatric patients. More specifically, we sought to evaluate whether it would be better to propose contextualized games or just distracting activities. A total of 104 children undergoing surgery were assigned to the following 4 conditions of treatment: (1) contextual games and psychological accompaniment, (2) only contextual games, (3) distracting activities, and (4) only psychological accompaniment. Observed children's anxiety was assessed using modified Yale Preoperative Anxiety Scale and compliant behaviours with modified form of Induction Compliance Checklist. Children in the first condition (complete intervention - contextual games and psychological accompaniment) were less anxious and more cooperative in the preoperative period and during the induction of anaesthesia than in the other three conditions. In particular, contextual activities (second condition) were found to be more efficient than psychological accompaniment (fourth condition), whereas the worst condition was proposing only distracting activities (third condition). In order to help young hospitalized patients in paediatric surgery structures, it is necessary to propose games that can prepare them for what will happen as well as the support of a psychologist.

  5. Real-time analysis of imatinib- and dasatinib-induced effects on chronic myelogenous leukemia cell interaction with fibronectin.

    Directory of Open Access Journals (Sweden)

    Adam Obr

    Full Text Available Attachment of stem leukemic cells to the bone marrow extracellular matrix increases their resistance to chemotherapy and contributes to the disease persistence. In chronic myelogenous leukemia (CML, the activity of the fusion BCR-ABL kinase affects adhesion signaling. Using real-time monitoring of microimpedance, we studied in detail the kinetics of interaction of human CML cells (JURL-MK1, MOLM-7 and of control BCR-ABL-negative leukemia cells (HEL, JURKAT with fibronectin-coated surface. The effect of two clinically used kinase inhibitors, imatinib (a relatively specific c-ABL inhibitor and dasatinib (dual ABL/SRC family kinase inhibitor, on cell binding to fibronectin is described. Both imatinib and low-dose (several nM dasatinib reinforced CML cell interaction with fibronectin while no significant change was induced in BCR-ABL-negative cells. On the other hand, clinically relevant doses of dasatinib (100 nM had almost no effect in CML cells. The efficiency of the inhibitors in blocking the activity of BCR-ABL and SRC-family kinases was assessed from the extent of phosphorylation at autophosphorylation sites. In both CML cell lines, SRC kinases were found to be transactivated by BCR-ABL. In the intracellular context, EC50 for BCR-ABL inhibition was in subnanomolar range for dasatinib and in submicromolar one for imatinib. EC50 for direct inhibition of LYN kinase was found to be about 20 nM for dasatinib and more than 10 µM for imatinib. Cells pretreated with 100 nM dasatinib were still able to bind to fibronectin and SRC kinases are thus not necessary for the formation of cell-matrix contacts. However, a minimal activity of SRC kinases might be required to mediate the increase in cell adhesivity induced by BCR-ABL inhibition. Indeed, active (autophosphorylated LYN was found to localize in cell adhesive structures which were visualized using interference reflection microscopy.

  6. Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patients with Plexiform Neurofibromas

    Science.gov (United States)

    2013-07-01

    Mesylate (STI-571, NSC 716051) In Neurofibromatosis ( NF1 ) Patients with Plexiform Neurofibromas PRINCIPAL INVESTIGATOR: Kent Robertson, M.D...Imatinib Mesylate (STI-571, NSC 716051) In Neurofibromatosis ( NF1 ) Patients with Plexiform Neurofibromas 5b. GRANT NUMBER W81XWH-09-1-0120 5c. PROGRAM...Section I - Introduction of research The goal of this Pilot Study is to trial multiple techniques for determining the response of NF1 patients with

  7. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    Energy Technology Data Exchange (ETDEWEB)

    Kinsella, Paula, E-mail: paula.kinsella@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Howley, Rachel, E-mail: rhowley@rcsi.ie [Department of Neuropathology, Beaumont Hospital, Dublin 9 (Ireland); Doolan, Padraig, E-mail: padraig.doolan@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Clarke, Colin, E-mail: colin.clarke@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Madden, Stephen F., E-mail: maddens@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Clynes, Martin, E-mail: Martin.Clynes@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Farrell, Michael, E-mail: michaelfarrell@beaumont.ie [Department of Neuropathology, Beaumont Hospital, Dublin 9 (Ireland); Amberger-Murphy, Verena, E-mail: Verena.Murphy@icorg.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); All Ireland Co-operative, Oncology Research Group, 60 Fitzwilliam Square, Dublin 2 (Ireland)

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC{sub 50}). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-{alpha} expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: Black-Right-Pointing-Pointer Non-responders had low EGFR expression, high PDGFR-{beta}, and a low proliferation rate. Black-Right-Pointing-Pointer PTEN is not indicative of response to a TKI. Black-Right-Pointing-Pointer Erlotinib response was not associated with expression of the proteins examined. Black-Right-Pointing-Pointer Imatinib-response correlated with expression of PDGFR-{alpha}. Black-Right-Pointing-Pointer Gefitinib response correlated with increased expression of EGFR.

  8. Preoperative easily misdiagnosed telangiectatic osteosarcoma: clinical–radiologic–pathologic correlations

    Science.gov (United States)

    Gao, Zhen-Hua; Yin, Jun-Qiang; Liu, Da-Wei; Meng, Quan-Fei

    2013-01-01

    Abstract Purpose: To describe the clinical, imaging, and pathologic characteristics and diagnostic methods of telangiectatic osteosarcoma (TOS) for improving the diagnostic level. Materials and methods: The authors retrospectively reviewed patient demographics, serum alkaline phosphatase (AKP) levels, preoperative biopsy pathologic reports, pathologic materials, imaging findings, and treatment outcomes from 26 patients with TOS. Patient images from radiography (26 cases) and magnetic resonance (MR) imaging (22 cases) were evaluated by 3 authors in consensus for intrinsic characteristics. There were 15 male and 11 female patients in the study, with an age of 9–32 years (mean age 15.9 years). Results: Eighteen of 26 patients died of lung metastases within 5 years of follow-up. The distal femur was affected more commonly (14 cases, 53.8%). Regarding serum AKP, normal (8 cases) or mildly elevated (18 cases) levels were found before preoperative chemotherapy. Radiographs showed geographic bone lysis without sclerotic margin (26 cases), cortical destruction (26 cases), periosteal new bone formation (24 cases), soft-tissue mass (23 cases), and matrix mineralization (4 cases). The aggressive radiographic features of TOS simulated the appearance of conventional high-grade intramedullary osteosarcoma, though different from aneurysmal bone cyst. MR images demonstrated multiple big (16 cases) or small (6 cases) cystic spaces, fluid-fluid levels (14 cases), soft-tissue mass (22 cases), and thick peripheral and septal enhancement (22 cases). Nine of 26 cases were misdiagnosed as aneurysmal bone cysts by preoperative core-needle biopsy, owing to the absence of viable high-grade sarcomatous cells in the small tissue samples. Conclusion: The aggressive growth pattern with occasional matrix mineralization, and multiple big or small fluid-filled cavities with thick peripheral, septal, and nodular tissue surrounding the fluid-filled cavities are characteristic imaging features of

  9. Preoperative education for lumbar surgery for radiculopathy

    Directory of Open Access Journals (Sweden)

    A. Louw

    2009-02-01

    Full Text Available To date no studies have been published on preoperative education forpatients who had lumbar surgery. The aim of this study was to determine if there is a demand for preoperative education for patients who had lumbar surgery for radiculopathy. A convenience sample of 47 patients who had lumbar surgery and a random sample of 141 physiotherapists involved in treating patients who had lumbar surgery completed a newly developed spinal surgery questionnaire. The data were analyzed using descriptiveand inferential statistical tests. Results showed that 100% of the patients and 99% of therapists view preoperative education to be an important component for lumbar surgery for radiculopathy. The most important factors identifiedfor inclusion in preoperative educational programs were reason for surgery, risks associated with surgery, limitations following surgery and more education regarding pain. The preferred method of education delivery was verbal one-on-one education. This study demonstrates that there is a demand for preoperative education for patients who had lumbar surgery.

  10. [Preoperative assessment of lung disease patients.].

    Science.gov (United States)

    Ramos, Gilson; Ramos Filho, José; Pereira, Edísio; Junqueira, Marcos; Assis, Carlos Henrique C

    2003-02-01

    Lung complications are the most frequent causes of postoperative morbidity-mortality, especially in lung disease patients. So, those patients should be preoperatively carefully evaluated and prepared, both clinically and laboratorially. This review aimed at determining surgical risk and at establishing preoperative procedures to minimize peri and postoperative morbidity-mortality in lung disease patients. Major anesthetic-surgical repercussions in lung function have already been described. Similarly, we tried to select higher-risk patients, submitted or not to lung resection. To that end, clinical and laboratorial propedeutics were used. Finally, a proposal of a preoperative algorithm was presented for procedures with lung resection. Lung disease patients, especially those with chronic evolution, need to be preoperatively thoroughly evaluated. ASA physical status and Goldmans cardiac index are important risk forecasting factors for lung disease patients not candidates for lung resection. Adding to these criteria, estimated postoperative max VO2, FEV1 and diffusion capacity are mandatory for some patients submitted to lung resection. beta2-agonists and steroids should be considered in the preoperative period of these patients.

  11. Nilotinib and imatinib are comparably effective in reducing growth of human eosinophil leukemia cells in a newly established xenograft model.

    Directory of Open Access Journals (Sweden)

    Daniel Wicklein

    Full Text Available We developed a xenograft model of human Chronic Eosinophilic Leukemia (CEL to study disease progression and remission-induction under therapy with tyrosine kinase inhibitors using imatinib and nilotinib as examples. The FIP1L1/PDGFRA+ human CEL cell lineEOL-1 was injected intravenously into scid mice, and MR imaging and FACS analysis of mouse blood samples were performed to monitor disease development and the effects of imatinib and nilotinib. Organ infiltration was analyzed in detail by immunohistochemistry after sacrifice. All animals developed CEL and within one week of therapy, complete remissions were seen with both imatinib and nilotinib, resulting in reduced total tumor volumes by MR-imaging and almost complete disappearance of EOL-1 cells in the peripheral blood and in tissues. The new model system is feasible for the evaluation of new tyrosine kinase inhibitors and our data suggest that nilotinib may be a valuable additional targeted drug active in patients with FIP1L1/PDGFRA+ CEL.

  12. ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF SOLID DOSAGE FORM OF ANTINEOPLASTIC DRUG IMATINIB MESILATE BY RP HPLC.

    Directory of Open Access Journals (Sweden)

    G. Sathwik

    2015-04-01

    Full Text Available A simple and sensitive High Performance Liquid Chromatographic method has been established and validated for Imatinib Mesylate in pharmaceutical dosage form, separation was performed on a C18, 150×4.6 mm, 5μ column in isocratic mode, with mobile phase containing a mixture of buffer: acetonitrile (72:28 v/v. The mobile phase was pumped at a flow rate of 1.0 ml/min and eluents were monitored at 265 nm. Linearity was found to be in the range of levels 80% to 120% and retention time was 3.63 min. The statistical validation parameters such as linearity, accuracy, precision, and specificity, limit of detection, limit of quantification were checked. The samples were prepared in water and the stability of Imatinib mesylate in aqueous solution at 30°C was studied. The results were satisfactory with good stability after 24 h at 30°C. The proposed method can be used for the related substances of Imatinib mesylate.

  13. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.

    LENUS (Irish Health Repository)

    Kinsella, Paula

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC(50)). Response for each culture was compared with the EGFR\\/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile.

  14. New HPLC-MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib, and nilotinib in human plasma.

    Science.gov (United States)

    De Francia, Silvia; D'Avolio, Antonio; De Martino, Francesca; Pirro, Elisa; Baietto, Lorena; Siccardi, Marco; Simiele, Marco; Racca, Silvia; Saglio, Giuseppe; Di Carlo, Francesco; Di Perri, Giovanni

    2009-06-15

    A new method using high performance liquid chromatography coupled with electrospray mass spectrometry is described for the quantification of plasma concentration of tyrosine kinase inhibitors imatinib, dasatinib and nilotinib. A simple protein precipitation extraction procedure was applied on 250 microl of plasma aliquots. Chromatographic separation of drugs and Internal Standard (quinoxaline) was achieved with a gradient (acetonitrile and water + formic acid 0.05%) on a C18 reverse phase analytical column with 20min of analytical run, at flow rate of 1 ml/min. Mean intra-day and inter-day precision for all compounds were 4.3 and 11.4%; mean accuracy was 1.5%; extraction recovery ranged within 95 and 114%. Calibration curves ranged from 10,000 to 62.5 ng/ml. The limit of quantification was set at 78.1 ng/ml for imatinib and at 62.5 ng/ml for dasatinib and nilotinib. This novel developed methodology allows a specific, sensitive and reliable simultaneous determination of the three tyrosine kinase inhibitors imatinib, dasatinib and nilotinib in a single chromatographic run, useful for drugs estimation in plasma of patients affected by chronic myeloid leukemia.

  15. Treatments for chronic myeloid leukemia: a qualitative systematic review

    Directory of Open Access Journals (Sweden)

    Ferdin

    2012-08-01

    Full Text Available Roxanne Ferdinand,1 Stephen A Mitchell,2 Sarah Batson,2 Indra Tumur11Pfizer, Tadworth, UK; 2Abacus International, Bicester, UKBackground: Chronic myeloid leukemia (CML is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients.Methods: Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature.Results: In the first-line setting, the long-term efficacy (up to 8 years of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]. All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR, major molecular response (MMR, and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment. Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates.Conclusion: Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response

  16. Autophagy induction by Bcr-Abl-expressing cells facilitates their recovery from a targeted or nontargeted treatment.

    LENUS (Irish Health Repository)

    Crowley, Lisa C

    2012-01-31

    Although Imatinib has transformed the treatment of chronic myeloid leukemia (CML), it is not curative due to the persistence of resistant cells that can regenerate the disease. We have examined how Bcr-Abl-expressing cells respond to two mechanistically different therapeutic agents, etoposide and Imatinib. We also examined Bcr-Abl expression at low and high levels as elevated expression has been associated with treatment failure. Cells expressing low levels of Bcr-Abl undergo apoptosis in response to the DNA-targeting agent (etoposide), whereas high-Bcr-Abl-expressing cells primarily induce autophagy. Autophagic populations engage a delayed nonapoptotic death; however, sufficient cells evade this and repopulate following the withdrawal of the drug. Non-Bcr-Abl-expressing 32D or Ba\\/F3 cells induce both apoptosis and autophagy in response to etoposide and can recover. Imatinib treatment induces both apoptosis and autophagy in all Bcr-Abl-expressing cells and populations rapidly recover. Inhibition of autophagy with ATG7 and Beclin1 siRNA significantly reduced the recovery of Imatinib-treated K562 cells, indicating the importance of autophagy for the recovery of treated cells. Combination regimes incorporating agents that disrupt Imatinib-induced autophagy would remain primarily targeted and may improve response to the treatment in CML.

  17. Imatinib and nilotinib inhibit hematopoietic progenitor cell growth, but do not prevent adhesion, migration and engraftment of human cord blood CD34+ cells.

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    Ludovic Belle

    Full Text Available BACKGROUND: The availability of tyrosine kinase inhibitors (TKIs has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine kinase of the stem cell factor receptor, c-Kit. Nilotinib is 30 times more potent than imatinib towards BCR-ABL in vitro. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors have shown that therapeutic doses of nilotinib deliver drug levels similar to those of imatinib. The aim of this study was to compare the inhibitory effects of imatinib and nilotinib on proliferation, differentiation, adhesion, migration and engraftment capacities of human cord blood CD34(+ cells. DESIGN AND METHODS: After a 48-hour cell culture with or without TKIs, CFC, LTC-IC, migration, adhesion and cell cycle analysis were performed. In a second time, the impact of these TKIs on engraftment was assessed in a xenotransplantation model using NOD/SCID/IL-2Rγ (null mice. RESULTS: TKIs did not affect LTC-IC frequencies despite in vitro inhibition of CFC formation due to inhibition of CD34(+ cell cycle entry. Adhesion of CD34(+ cells to retronectin was reduced in the presence of either imatinib or nilotinib but only at high concentrations. Migration through a SDF-1α gradient was not changed by cell culture in the presence of TKIs. Finally, bone marrow cellularity and human chimerism were not affected by daily doses of imatinib and nilotinib in a xenogenic transplantation model. No significant difference was seen between TKIs given the equivalent affinity of imatinib and nilotinib for KIT. CONCLUSIONS: These data suggest that combining non-myeloablative conditioning regimen with TKIs starting the day of the transplantation could be safe.

  18. First-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia in adults.

    Science.gov (United States)

    Ottmann, Oliver G; Pfeifer, Heike

    2009-06-01

    The tyrosine kinase inhibitor (TKI) imatinib has become an integral part of front-line therapy for Philadelphia chromosome-positive acute lymphoblastic leukaemia, with remission rates exceeding 90% irrespective of whether imatinib is given alone or combined with chemotherapy. Treatment outcome with imatinib-based regimens has improved compared with historic controls, but most patients who do not undergo allogeneic stem cell transplantation (SCT) eventually relapse. Second-generation TKI, e.g. dasatinib and nilotinib, show activity against most of the bcr-abl tyrosine kinase domain mutations involved in acquired imatinib resistance, but clinical benefit is generally short lived. Accordingly, SCT in first complete response is considered to be the best curative option. Strategies to improve outcome in patients ineligible for transplantation as well as after SCT include front-line treatment with more effective TKI to increase molecular response rates. Following SCT, the pre-emptive use of imatinib appears to reduce the relapse rate. Novel immunotherapeutic interventions and combinations of TKI are also being explored.

  19. Phase 1 study of INNO-406, a dual Abl/Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias after imatinib resistance or intolerance.

    Science.gov (United States)

    Kantarjian, Hagop; le Coutre, Phillipp; Cortes, Jorge; Pinilla-Ibarz, Javier; Nagler, Arnon; Hochhaus, Andreas; Kimura, Shinya; Ottmann, Oliver

    2010-06-01

    : INNO-406, a dual v-abl Abelson murine leukemia viral oncogene homolog (Abl)/v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog (Lyn) tyrosine kinase inhibitor (TKI), has demonstrated specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. Several breakpoint cluster region (Bcr)-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including mutations that involve a phenylalanine-to-leucine or phenylalanine-to-valine substitution at codon 317 (F317L and F317V, respectively). In the current study, the authors evaluated the use of INNO-406 in patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) after imatinib resistance or intolerance. : A dose-escalation study was conducted at a starting dose of oral INNO-406 30 mg once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily dosing also was evaluated. Therapy was allowed to continue for a maximum of 24 months. : INNO-406 was administered to 56 patients with imatinib resistance (n = 40) or intolerance (n = 16). Other previous treatments included nilotinib (n = 20 patients), dasatinib (n = 26 patients), and dasatinib/nilotinib (n = 9 patients). Common mutations at the time of study entry included a tyrosine-to-histidine substitution at codon 253 (Y253H) (n = 6 patients), a glycine-to-glutamic acid substitution at codon 250 (G250E) (n = 4 patients), a threonine-to-isoleucine substitution at codon 315 (T315I) (n = 4 patients), and F317L (n = 3 patients). Of 31 patients with CML in chronic phase who received INNO-406, the major cytogenetic response rate was 19%. No responses were observed in patients who had CML in accelerated phase, CML in blastic phase, or Ph-positive ALL. The dose-limiting toxicities (DLTs) at an INNO-406 dose of 480 mg twice daily were liver function abnormalities and

  20. Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism with Chronic Myeloid Leukemia (CML in Patients Undergoing Imatinib Therapy

    Directory of Open Access Journals (Sweden)

    Samyuktha Lakkireddy

    2015-10-01

    Full Text Available Objective: Cytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association between single nucleotide polymorphisms (SNPs in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM affecting clinico-pathological parameters, in the Indian population. Materials and Methods: In this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genomic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2C polymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters. Results: We observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs. 16%, P=0.0001, AG (57 vs. 78%, P=0.0002 and GG (5 vs. 6%, P=0.6635 between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs AG in major (33 vs 67% and poor (62 vs 31% hematological responders, and AA vs AG in major (34 vs. 65% and poor (78 vs. 22% cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome. Conclusion: The higher frequency of AG in controls indicates that AG may play a protective role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards imatinib therapy, indicating

  1. Downregulated microRNA-148b in circulating PBMCs in chronic myeloid leukemia patients with undetectable minimal residual disease: a possible biomarker to discontinue imatinib safely

    Directory of Open Access Journals (Sweden)

    Ohyashiki JH

    2014-08-01

    and may therefore have potential as additive information in managing CML patients undergoing treatment with IM. Keywords: chronic myeloid leukemia, imatinib mesylate, discontinuation, miR-148b 

  2. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST after imatinib failure - one institution study

    Directory of Open Access Journals (Sweden)

    Rutkowski Piotr

    2012-03-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM or sunitinib (SU. Arterial hypertension (AH is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+ GIST patients after IM failure. Methods We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment. Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs of VEGFA and VEGFR2 genes. Results One year progression-free survival (PFS; calculated from the start of SU rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks in 55 patients with AH vs. 22% (median 17 weeks in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively. We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism

  3. Pre-operative fasting guidelines: an update

    DEFF Research Database (Denmark)

    Søreide, E; Eriksson, L I; Hirlekar, G

    2005-01-01

    Liberal pre-operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children......Liberal pre-operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children...

  4. Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

    Institute of Scientific and Technical Information of China (English)

    Jin-Zhong Yuan; Qi-Fa Ye; Ling-Ling Zhao; Ying-Zi Ming; Hong Sun; Shai-Hong Zhu; Zu-Fa Huang; Min-Min Wang

    2006-01-01

    AIM: To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT).METHODS: Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d)after OLT.RESULTS: In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34patients within 30d observation was: 28 kept alive and 6patients died.CONCLUSION: Pre-operative SOFA, level of creatinine,INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly.

  5. [Valvular heart disease: preoperative assessment and postoperative care].

    Science.gov (United States)

    Nägele, Reto; Kaufmann, Beat A

    2013-10-30

    Patients with valvular heart disease or with a prosthetic heart valve replacement are seen with increasing frequency in clinical practice. The medical care and evaluation of patients with valvular heart disease before valve surgery, but also the post-operative treatment is complex and managed by general practitioners, cardiologists and cardiac surgeons. In this mini-review we will first discuss the preoperative assessment of the two most common valvulopathies, aortic stenosis and mitral regurgitation. Then we will discuss the post-operative care, which includes the management of anticoagulation, serial follow up and as well as the diagnostic assessment of complications such as thromboembolism, hemolysis, endocarditis and valve dysfunction.

  6. Preoperative staging of lung cancer with combined PET-CT

    DEFF Research Database (Denmark)

    Fischer, Barbara; Lassen, Ulrik; Mortensen, Jann

    2009-01-01

    BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC...... one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause...

  7. Preoperative arterial embolization in heterotopic ossification: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Balzer, J. [Dept. of Radiology, University of Frankfurt (Germany); Wolff, J.D. [Dept. of Cardiothoracic Surgery, University of Frankfurt (Germany); Skripitz, R. [Dept. of Orthopaedic Surgery, University of Frankfurt (Germany)

    2001-06-01

    We report a case of preoperative embolization in a 64-year-old patient suffering from total stiffness of the right hip joint due to heterotopic ossification following brain injury and pertrochanteric fracture of the right femur. A previous attempt of operative treatment could not be performed successfully due to bleeding complications. After the embolization of the correlating hypervascularisation, the surgical procedure was redone and finished with good result and minimal bleeding complications during the operation and a tolerable drop of the haemoglobin concentration postoperatively. (orig.)

  8. The effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism.

    Science.gov (United States)

    Yilmaz, Yeliz; Kamer, Kemal Erdinc; Ureyen, Orhan; Sari, Erdem; Acar, Turan; Karahalli, Onder

    2016-08-01

    To investigate the effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism. This controlled, randomized, prospective cohort was carried out on 40 patients who admitted for surgery due to hyperthyroidism. Cases were randomly assigned to receive either preoperative treatment with Lugol solution (Group 1) or no preoperative treatment with Lugol solution (Group 2). Group 3 (n = 10) consisted of healthy adults with no known history and signs of hyperthyroidism. Blood flow through the thyroid arteries of patients was measured by color flow Doppler ultrasonography. Free T3, free T4, TSH, thyroid volume and the resistance index of the four main thyroid arteries were measured in all patients. There was not a significant difference between gender, preoperative serum thyroid hormone levels, or thyroid gland volumes between groups 1 and 2. The mean blood flow of the patients in Group 1 was significantly lower than values in Group 2. When age, gender, thyroid hormone, TSH, thyroid volume, blood flow, and Lugol solution treatment were included as independent variables, Lugol solution treatment (OR, 7.40; 95% CI, 1.02-58.46; p = 0.001) was found to be the only significant independent determinant of intraoperative blood loss. Lugol solution treatment resulted in a 7.40-fold decrease in the rate of intraoperative blood loss. Preoperative Lugol solution treatment was found to be a significant independent determinant of intraoperative blood loss. Moreover, preoperative Lugol solution treatment decreased the rate of blood flow, and intraoperative blood loss during thyroidectomy.

  9. Response to treatment in women with chronic myeloid leukemia during pregnancy and after delivery.

    Science.gov (United States)

    Klamová, Hana; Marková, Markéta; Moravcová, Jana; Sisková, Magda; Cetkovský, Petr; Machová Poláková, Katerina

    2009-11-01

    Here we report response to treatment of chronic myeloid leukemia (CML) of five pregnant women during and after pregnancy. CML was diagnosed during pregnancy in three patients. Pregnancy was confirmed during CML in two patients: in one in the 21st week of pregnancy while on imatinib, in another in the 12th week during the interferon treatment. Interferon with leukapheresis when needed was applied in the 2nd and 3rd trimester. All patients except one achieved complete hematological response during pregnancy. After delivery four patients achieved partial cytogenetic response on imatinib and two patients achieved major molecular response after crossover to dasatinib.

  10. Chronic myelocytic leukemia in pregnancy: a case report describing successful treatment using multimodal therapy.

    Science.gov (United States)

    Eskander, Ramez N; Tarsa, Maryam; Herbst, Kenneth D; Kelly, Thomas F

    2011-11-01

    Leukemia during pregnancy is rare, posing a complex series of questions, including appropriate therapy and maternal counseling. Management of chronic myelocytic leukemia (CML) during pregnancy is limited. Our patient presented at 30 weeks' gestation with anemia, leukocytosis, and a non-productive cough. Polymerase chain reaction performed on a peripheral blood sample confirmed presence of the breakpoint cluster region-Abl1 chromosomal translocation and the diagnosis of CML. Therapy included acute leukocytapheresis, followed by α-interferon and imatinib mesylate. The patient responded to treatment and delivered a viable female infant at term weighing 2613 g. Continued imatinib mesylate chemotherapy post-delivery resulted in complete clinical remission. Successful antepartum management of newly diagnosed CML is possible utilizing leukocytapheresis, α-interferon and, more recently, imatinib mesylate. Definitive treatment should not be delayed due to pregnancy.

  11. Effect of music treatment on nursing quality in preoperative waiting room%音乐疗法对术前等候室护理质量的影响

    Institute of Scientific and Technical Information of China (English)

    吴兴娇; 高丽娟; 王传光; 程锐; 吴炜; 雷李培