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EFFICACY OF ifosfamide AND VP-16 (ETOPOSIDE) IN PATIENTS WITH SMALL CELL LUNG CANCER AND THE CORRELATION BETWEEN MICROVESSEL COUNT ON CHEMOSENSITIVITY

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Chinese Journal of Cancer Research 2006年第2期18卷 116-120页

作者：王斯闻刘宏旭李玉 Department of Internal Medicine Fourth Hospital China Medical University Shenyang 110001 Department of Thoracic Surgery First Hospital China Medical University Shenyang 110001

Objective： To evaluate the efficacy of ifosfamide and etoposide （VP-16） in patients with small cell lung cancer （SCLC）, and investigate the correlation between microvessel count （MVC） in tumor and chemotherapeutic sensitivity. Methods： Forty-one consecutive cases of SCLC received chemotherapy of ifosfamide plus VP-16, and underwent investigation retrospectively. Immunohistochemistry using anti-human blood type H monoclonal antibody was conducted and MVC was recorded under light microscope. Results： There were 27 limited-disease and 14 extensive-disease patients. The overall response rate was 92.7% （38/41） with 28 cases （68.3%） of complete response （CR）, 10 （24.4%） with partial response （PR）, 3 （7.3%） with progressive disease （PD）. The 1-, 2-, 3-, and 5-year survival rates were 68.3% （28/41）, 48.3% （20/41）, 23.7% （9/38） and 11.1% （3/27）, respectively, with the median survival of 26.8 months. The principal toxicities were grade 3-4 neutropenia in 8 cases （19.5%）, grade 3-4 thrombocytopenia in 6 cases （14.6%）, mild liver toxicity in 7 cases （17.0%） and mild renal function damage in 4 cases （9.8%）. The mesenchymal vasculature was clearly visualized, with the mean value of 34.7 under each high microscopic power field. Of SCLC with more MVC （n=26）, CR accounted for 84.6%; while in cancers with less MVC （n=l 5）, CR took up 40.0%, with significant difference （P〈0.05）. Conclusion： Administrating ifosfamide and VP-16 is in accordance with the biological features of SCLC and results in beneficial results as well as acceptable side effects. The MVC is positively correlated with the chemotherapeutic sensitivity, and serves as a vital factor contributing to chemosensitivity.

关键词： ifosfamide VP-16 Small cell lung cancer Mierovessel count Chemosensitivity

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PEComa of the colon resistant to sirolimus but responsive to doxorubicin/ifosfamide

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World Journal of Gastroenterology 2013年第10期19卷 1657-1660页

作者： Wolfgang Scheppach Nikolaus Reissmann Thomas Sprinz Ekkehard Schippers Bjoern Schoettker Justus G Mueller Department of Medicine Juliusspital WuerzburgD-97070 WuerzburgGermany Department of Surgery Juliusspital WuerzburgD-97070 WuerzburgGermany Onkologische Schwerpunktpraxis D-97070 WuerzburgGermany Department of Pathology University of Wuerzburg97070 WürzburgGermany

A 23-year-old male presented with a three-week-history of crampy abdominal pain and *** revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular epithelioid cell tumor(PEComa).An magnetic resonance imaging scan showed,in addition to the primary tumor,two large mesenteric lymph node metastases and four metastatic lesions in the *** patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver,the resection status was ***,the patient was treated with *** 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic *** visible tumor formations were again excised surgically,this time the resection status was R2 with regard to the pelvic *** patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 *** clinical course was then determined by rapid tumor growth in the pelvic *** line chemotherapy with gemcitabine and docetaxel was ineffective,and the patient died 23 mo after the onset of *** case report adds evidence that,in malignant PEComa,the mainstay of treatment is curative *** not achievable,the effects of adjuvant or palliative chemotherapy are unpredictable.

关键词： Perivascular epithelioid cell tumor Colon Liver metastases Mammalian target of rapamycin inhibitor Sirolimus Chemotherapy Doxorubicin ifosfamide

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HIGH DOSE ifosfamide, DOXORUBICIN, DACARBAZINE AND G-CSF FOR PATIENTS WITH METASTATIC OR LOCALLYADVANCED SOFT TISSUE SARCOMA

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Chinese Journal of Cancer Research 1999年第3期11卷 200-203页

作者：林桐榆管忠震苏义顺周中梅刘冬耕 Department of Medical Oncology Cancer Center Sun Yat-sen University of Medical Sciences Guangzhou China

Objective: A pilot study to test the feasibility and efficacy of high dose IFO and standard dose ADR and DTIC with G-CSF support in treatment of advanced soft tissue sarcoma (STS). Methods: 35 patients of no prior chemotherapy with metastatic or locally advanced unresectable STS were treated by this regimen, including 18 rhabdomyosarcomas, 7 malignant fibrous histiocytomas, 2 neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2 synoviosarcomas, and 2 malignant hemangiopericytomas. IFO dose was 2 g/m2 on day 1–5 (with mesna uroprotection), ADR 50mg/m2 on day 1 and DTIC 250 mg/m2 on day 1–5. G-CSF (2 μg/kg/d) was administered on day 6 to 15 or until recovery of leukocytes account. The cycles were repeated every 3 weeks. Result: There were five complete responses (CR including pathologic CR) and eleven partial responses for overall 46% objective response rate. Most responses were observed within two cycles. The median survival was 15 months. Following CR, two patients remain disease free at 45 and 28 months, respectively. 6/120 (5%) cycles were complicated by grade IV neutropenia, 46/120 (38%) cycles had grade III neutropenia. No patients had treatment-related deaths. Nonhematologic toxicity consisted predominantly of anorexia and vomiting. No other severe toxicities were seen, especially no severe cardiotoxicity. Conclusion: This regimen is well tolerated and has substantial benefits for patients with advanced soft tissue sarcomas.

关键词： Soft tissue sarcoma ifosfamide high dose Chemetherapy

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Retrospective analysis of patients with rare-site and metastatic giant cell tumor

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Chinese Journal of Cancer Research 2013年第5期25卷 585-592页

作者： Junling Liu Han Yang Rui Sun Zhijun Yang Zhihua Zhu State Key Laboratory of Oncology in South China Department of Medical Oncology Sun Yat-sen University Cancer Center Department of Thoracic Surgery Sun Yat-sen University Cancer Center Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer Center

A giant cell tumor occurs mainly in the proximal tibia,humerus,distal radius bone and the pelvic *** is rarely observed in such sites as the ribs and the temporal *** condition is primarily treated with surgical excision and functional *** effect of chemotherapy on lung metastases and locally advanced giant cell tumors has remained *** collected and analyzed the data of six patients with rare giant cell tumors located in the head and neck *** an average follow-up of 42.6 months after surgery （14 to 90 months）,no local recurrence or metastasis was *** also collected and analyzed the data of five patients with metastatic giant cell tumors who were undergoing surgery for the primary tumor before; of three patients who had experienced multiple chemotherapy cycles,one had spontaneous regression,and one survived for long timer despite *** other two patients had their major metastatic lesions resected by surgery,and presented long-term survival during the follow *** addition,this study reports one patient with locally advanced giant cell tumor of the rib,who has undergone successful surgical resection following two cycles of chemotherapy with ifosfamide and liposomal *** resection of the lesion at the head and neck is the key to relapse-free *** prognosis of lung metastases in patients with giant cell tumors is relatively *** chemotherapy is also conducive to the surgery for locally advanced lesions and improvement of the quality of life.

关键词： Giant cell tumor neoadjuvant chemotherapy ifosfamide liposomal doxorubicin

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Extravascular use of drug-eluting beads: A promising approach in compartment-based tumor therapy

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World Journal of Gastroenterology 2013年第43期19卷 7586-7593页

作者： Simon Binder Andrew L Lewis J-Matthias Lhr Michael Keese Faculty of Medicine Mannheim University of Heidelberg68167 MannheimGermany Biocompatibles UK Ltd. Department for Research and DevelopmentFarnham GU98QL SurreyUnited Kingdom Karolinska Institute Department of Clinical ScienceIntervention and Technology17177 StockholmSweden Clinic for Vascular and Endovascular Surgery University Hospital Frankfurt60590 Frankfurt am MainGermany

Intraperitoneal carcinomatosis(PC)may occur with several tumor *** prognosis of patients suffering from PC is usually *** treatment depends on the cancer entity and includes systemic chemotherapy,radiation therapy,hormonal therapy and surgical *** few patients may also benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor *** therapies are often accompanied by severe systemic *** approach to reduce side effects is to target chemotherapeutic agents to the tumor with carrier *** experimental results have been achieved using drug-eluting beads(DEBs).A series of in vitro and in vitro experiments has been conducted to determine the suitability of their extravascular *** encapsulation devices were able to harbor CYP2B1producing cells and to shield them from the hosts immune system when injected *** this way ifosfamide-which is transformed into its active metabolites by CYP2B1-could be successfully targeted into pancreatic tumor *** DEBs can be used to target chemotherapeutics into the abdominal cavity for treatment of *** CYP2B1 producing cells are proven to be save for usage in man and if local toxic effects of chemotherapeutics can be controlled,DEBs will become promising tools in compartmentbased anticancer treatment.

关键词： Compartment based therapy Intraperitoneal Drug-eluting beads Carcinomatosis Hyperthermic intraperitoneal chemotherapy Glioblastoma Pancreatic cancer CYP2B1 ifosfamide

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Enzyme activity analysis of CYP2C18 with exon 5 skipped

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Acta Pharmacologica Sinica 2004年第8期 91-95页

作者： Jian ZHU-GE, Ying-nian YUDepartment of Pathophysiology, Center for Environmental Genomics, Zhejiang University School of Medicine, Hangzhou 310031, China

AIM: To study the enzyme activity of CYP2C18 variant with exon 5 skipped. METHODS: A full length CYP2C18 cDNA X1 and an exon 5 skipped variant CYP2C18 X2 were separately subcloned into mammalian expression vector pREP9 to transfect HepG2 cells. The expression of CYP2C18 mRNA in transgenic cells and human liver tissues were determined by RT-PCR. The enzyme activity of CYP2C18 to oxidate tolbutamide in postmitochondrial supernate (S9) fraction was determined by HPLC. The cytotoxicity of ifosfamide to transgenic cells was evaluated by MTT test. RESULTS: HepG2-CYP2C18 X1 cells showed strong expression of the full length CYP2C18 mRNA. On the other hand, HepG2-CYP2C18 X2 cells had only infinitesimal expression of the exon-skipped CYP2C18 as well as the full length CYP2C18, while non-transfected HepG2 cell only demonstrated an infinitesimal expression of the full length CYP2C18. The expression of CYP2C18 exons 2 to 7 was also analyzed by RT-PCR in 7 extratumoral liver tissues. Among them, 3 samples expressed on

关键词： human CYP2C18 protein tolbutamide ifosfamide

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Comprehensive management of epithelial ovarian cancer with peritoneal metastases

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World Journal of Obstetrics and Gynecology 2013年第4期2卷 108-115页

作者： Luigi Frigerio Luca Ansaloni Elia Poiasina Federico Coccolini Paul H Sugarbaker Obstetrics and Gynecology Department OspedaliRiuniti 24128 Bergamo Italy General and Emergency Surgery Department Ospedali Riuniti 24128 Bergamo Italy Washington Cancer Institute Washington Hospital Center Washington DC 20010 United States

Ovarian cancer has as its predominant pattern of dissemination metastases to the peritoneal surfaces and disease spread within the abdomen and pelvis that most commonly causes the patients demise. To combat peritoneal metastases, cytoreductive surgery with peritoneal and visceral resections is combined with intraperitoneal and systemic chemotherapy. Chemotherapy given in the operating room after the complete visible removal of ovarian cancer is hyperthermic intraperitoneal chemotherapy. The results of the combined treatment are determined by the extent of prior surgery, the extent of disease as established by the peritoneal cancer index, and the quality of the cytoreduction as measured by the completeness of cytoreduction score. Recent clinical information on patients with recurrent ovarian cancer suggest a median overall survival of up to 60 mo. These data are greatly improved over the one year survival observed in the past.

关键词： Peritoneal metastases Carcinomatosis Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Intraperitoneal chemotherapy Cisplatin Doxorubicin ifosfamide Mitomycin C Intraperitoneal port

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Pharmacology of cancer chemotherapy drugs for hyperthermic intraperitoneal peroperative chemotherapy in epithelial ovarian cancer

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World Journal of Obstetrics and Gynecology 2013年第4期2卷 143-152页

作者： Kurt Van der Speeten Anthony O Stuart Paul H Sugarbaker Department of Surgical Oncology Ziekenhuis Oost-Limburg 3600 Genk Belgium University Hasselt Life Sciences Faculty Oncology Research Cluster 3000 Hasselt Belgium Washington Cancer Institute Washington Hospital Center Washington DC 20010United States

The peritoneal parietal and visceral surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of epithelial ovarian cancer(EOC). The transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis(PC) which, without special treatments, is a fatal manifestation of EOC. In order to control PC cytoreductive surgery to remove macroscopic disease is combined with perioperative intraperitoneal(IP) and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the IP or intravenous route based on their pharmacologic properties. A peritoneal-plasma barrier which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration is facilitated by moderate hyperthermia(41-42 ℃) of the IP chemotherapy solution. Timing of the chemotherapy as a planned part of the surgical procedure to maximize expo-sure of all peritoneal surfaces is crucial to success.

关键词： Intraperitoneal chemotherapy Epithelial ovarian cancer ifosfamide Cisplatin Carboplatin Taxanes Pharmacokinetics Pharmacodynamics

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Oxazaphosphorine bioactivation and detoxification: the role of xenobiotic receptors

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Acta Pharmaceutica Sinica B 2012年第2期2卷 107-117页

作者： Duan Wang Hongbing Wang Department of Pharmaceutical Sciences School of PharmacyUniversity of MarylandBaltimoreUSA

Oxazaphosphorines,with the most representative members including cyclophosphamide,ifosfamide,and trofosfamide,constitute a class of alkylating agents that have a broad spectrum of anticancer activity against many malignant ailments including both solid tumors such as breast cancer and hematological malignancies such as leukemia and *** oxazaphosphorines are prodrugs that require hepatic cytochrome P450 enzymes to generate active alkylating moieties before manifesting their chemotherapeutic ***,oxazaphosphorines can also be transformed into non-therapeutic byproducts by various drug-metabolizing ***,oxazaphosphorines are often administered in combination with other chemotherapeutics in adjuvant *** such,the therapeutic efficacy,off-target toxicity,and unintentional drug–drug interactions of oxazaphosphorines have been long-lasting clinical concerns and heightened focuses of scientific *** evidence suggests that xenobiotic receptors may play important roles in regulating the metabolism and clearance of *** as modulators of xenobiotic receptors can affect the therapeutic efficacy,cytotoxicity,and pharmacokinetics of coadministered oxazaphosphorines,providing a new molecular mechanism of drug–drug ***,we review current advances regarding the influence of xenobiotic receptors,particularly,the constitutive androstane receptor,the pregnane X receptor and the aryl hydrocarbon receptor,on the bioactivation and detoxification of oxazaphosphorines,with a focus on cyclophosphamide and ifosfamide.

关键词： Oxazaphosphorine Cyclophosphamide ifosfamide CAR PXR CYP2B6

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Primary Ovarian Carcinosarcoma: Cytological, Pathological, Immunocytochemical, and Immunohistochemical Features

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Open Journal of Pathology 2021年第1期11卷 22-31页

作者： Kenji Niwa Sakae Mori Keigo Kuwabara Kentaro Nagata Motoki Takenaka Tomomi Shiga Yoshio Yamaguchi Kentaro Niwa Takuji Tanaka Department of Obstetrics & Gynecology Gujo City Hospital Gujo City Japan Section of Laboratory Medicine Gujo City Hospital Gujo City Japan Department of Obstetrics & Gynecology Gifu University School of Medicine Gifu City Japan Department of Obstetrics & Gynecology University of Fukui Hospital Eiheiji-cho Fukui Prefecture Japan Department of Diagnostic Pathology & Research Center of Diagnostic Pathology Gifu Municipal Hospital Gifu City Japan

Ovarian carcinosarcoma composed of high-grade carcinoma and sarcoma is an extremely rare neoplasm and typically occurs in postmenopausal women aged over 60 years. A 73-year-old female, gravida three para three, presented to our hospital with right lower abdominal pain. Right pelvic solid tumor with ascites was detected on pelvic ultrasound examination. She underwent hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy, but the tumor had invaded to the right ureter, and some fragile tumor could not be taken (sub-optimal surgery). On the imprint and ascitic cytology specimens during operation, atypical cells suggestive of adenocarcinoma and spindle atypical cells with immunocytochemically vimentin positive were found. The resected tumor was histopathologically carcinosarcoma consisted of serous adenocarcinoma, chondrosarcoma and fibrosarcoma. Immunohistochemical analysis revealed that adenocarcinoma cells were positive for AE1/AE3 and fibrosarcoma cells stained with vimentin. The final diagnosis was the right ovarian carcinosarcoma (stage pT3CNxMx). Microsatellite instability was stable and BRCA1/2 mutations could not be found in the carcinosarcoma cells. The patient was given four cycles of chemotherapy with paclitaxel, carboplatin and bevacizumab regimen, and thereafter she was treated with the ifosfamide and cisplatin because of slight elevation of serum CA125.

关键词： Ovary Carcinosarcoma Immunocytochemistry Immunohistochemistry ifosfamide Cisplatin

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