Ifosfamide Research Articles

Hypoxia increases chemoresistance in human medulloblastoma DAOY cells via hypoxia‑inducible factor 1α‑mediated downregulation of the CYP2B6, CYP3A4 and CYP3A5 enzymes and inhibition of cell proliferation.

Medulloblastomas are among the most frequently diagnosed pediatric solid tumors, and drug resistance remains as the principal cause of treatment failure. Hypoxia and the subsequent activation of hypoxia-inducible factor 1α (HIF-1α) are considered key factors in modulating drug antitumor effectiveness, but the underlying mechanisms in medulloblastomas have not yet been clearly understood. The aim of the present study was to determine whether hypoxia induces resistance to cyclophosphamide (CPA) and ifosfamide (IFA) in DAOY medulloblastoma cells, whether the mechanism is dependent on HIF-1α, and whether involves the modulation of the expression of cytochromes P450 (CYP)2B6, 3A4 and 3A5 and the control of cell proliferation. Monolayer cultures of DAOY medulloblastoma cells were exposed for 24 h to moderate (1% O2) or severe (0.1% O2) hypoxia, and protein expression was evaluated by immunoblotting. Cytotoxicity was studied with the MTT assay and by Annexin V/PI staining and flow cytometry. Cell proliferation was determined by the trypan-blue exclusion assay and cell cycle by propidium iodide staining and flow cytometry. Hypoxia decreased CPA and IFA cytotoxicity in medulloblastoma cells, which correlated with a reduction in the protein levels of CYP2B6, CYP3A4 and CYP3A5 and inhibition of cell proliferation. These responses were dependent on hypoxia-induced HIF-1α activation, as evidenced by chemical inhibition of its transcriptional activity with 2-methoxyestradiol (2-ME), which enhanced the cytotoxic activity of CPA and IFA and increased apoptosis. Our results indicate that by stimulating HIF-1α activity, hypoxia downregulates the expression of CYP2B6, CYP3A4 and CYP3A5, that in turn leads to decreased conversion of CPA and IFA into their active forms and thus to diminished cytotoxicity. These results support that the combination of HIF-1α inhibitors and canonical antineoplastic agents provides a potential therapeutic alternative against medulloblastoma.

Transformation kinetics of cyclophosphamide and ifosfamide by ozone and hydroxyl radicals using continuous oxidant addition reactors

The detection of pharmaceuticals in water and wastewater has triggered human and ecological health concerns. As highly toxic compounds, chemotherapy agents (CAs), such as the cyclophosphamide (CYP) and ifosfamide (IFO) structural isomers, represent a unique threat. This research elucidated the fate of CYP and IFO during ozonation and advanced oxidation by hydroxyl radicals (HO•). Novel semi-batch reactors were used to determine the second-order rate constants for CYP and IFO with O3 and HO•. These reactors provided independent control of the oxidant exposure through continuous and constant aqueous ozone and peroxone (O3-H2O2) addition. The rate constants for transformation of CYP and IFO by ozone were 2.58 ± 0.40 M-1s-1 and 6.95 ± 0.21 M-1s-1, respectively, indicating that ozone alone is not suitable for treating CAs. Transformation of CYP and IFO by hydroxyl radicals was fast, with rate constants of 2.69(±0.17)×109 M-1s-1 and 2.73(±0.16)×109 M-1s-1, respectively. The major transformation products formed by O3 and HO attack consisted of the 4-hydroxy-, 4-keto-, dechloroethyl-, and imino- derivatives of CYP and IFO. Low yields of the active metabolites of the CAs, namely phosphoramide mustard and isophosphoramide mustard, were detected. These findings suggest that treated water may retain the ability to alkylate DNA and confer toxicity.

Progress in the chemotherapeutic treatment of osteosarcoma.

Osteosarcoma (OS) is the most common type of primary bone tumor in children and adolescents and has been associated with a high degree of malignancy, early metastasis, rapid progression and poor prognosis. However, the use of adjuvant chemotherapy improves the prognosis of patients with OS. OS chemotherapy is based primarily on the use of adriamycin, cisplatin (DDP), methotrexate (MTX), ifosfamide (IFO), epirubicin (EPI) and other drugs. Previous studies have revealed that the survival rate for patients with OS appears to have plateaued: 5-year survival rates remain close to 60%, even with the use of combined chemotherapy. The most limiting factors include complications and fatal toxicity associated with chemotherapy agents, particularly high-dose MTX (HD-MTX), for which high toxicity and great individual variation in responses have been observed. Docetaxel (TXT) is a representative member of the relatively recently developed taxane class of drugs, which function to inhibit OS cell proliferation and induce apoptosis. Recently, more clinical studies have reported that TXT combined with gemcitabine (GEM) is effective in the treatment of OS (relapse/refractory and progressive), providing evidence in support of potential novel treatment strategies for this patient population. However, there is still no global consensus on this type of chemotherapy approach. The present review summarizes current studies surrounding progress in the chemotherapeutic treatment of OS and discusses the advantages and potential feasibility of TXT+GEM in the treatment of OS.

Au/Pd@rGO nanocomposite decorated with poly (L-Cysteine) as a probe for simultaneous sensitive electrochemical determination of anticancer drugs, Ifosfamide and Etoposide

The simultaneous measurement of the concentration of anticancer drugs with a fast, sensitive and accurate method in biological samples is a challenge for better monitoring of drug therapy and better determine the pharmacokinetics. An electrochemical sensor was developed for the simultaneous determination of anticancer drugs, Ifosfamide (IFO) and Etoposide (ETO) based on pencil graphite electrode modified with Au/Pd@rGO nanocomposite decorated with poly (L-Cysteine). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were utilized to study the properties of the modified electrode. The electrochemical behavior of IFO and ETO on the Au/Pd@rGO@p(L-Cys) modified electrode was investigated by cyclic voltammetry and differential pulse voltammetry (DPV) techniques and the obtained results confirmed its efficiency for the individual and simultaneous sensing of IFO and ETO. After optimization of electrochemical parameters, the fabricated sensor presented excellent performance in simultaneous determination of IFO and ETO with a wide linear range from 0.10 to 90.0 μM and 0.01 to 40.0 μM and low detection limits (3 Sb/m) of 9.210 nM and 0.718 nM, respectively. In addition, this study proved that the constructed sensor could be useful to simultaneous analysis of IFO and ETO in biological samples and pharmaceutical compounds.

Cytostatic drug removal using electrochemical oxidation with BDD electrode: Degradation pathway and toxicity

In the presented study, electrochemical oxidation of five anticancer drugs (5-fluorouracil (5-FU), ifosfamide (IF), cyclophosphamide (CF), methotrexate (MTX), imatinib (IMB)) using boron doped diamond (BDD) electrode was investigated. In the first step the operating parameters of electrolysis were optimized. Studies have demonstrated a significant influence of applying current density, temperature, pH of solution and initial concentration of 5-FU on the process efficiency. A comparison of the decomposition rate of all the tested drugs showed a decrease in the pseudo-first order rate constants in the following order: k(IMB) > k(MTX) > k(CF) ≈ k(IF) > k(5-FU). Mineralization current efficiency (MCE) was determined for all the drugs based on the removal amount of total organic carbon (TOC) and their values decreased in the same order as values of drug degradation rate k. Based on the identified degradation products, electrochemical oxidation pathways of the decomposed drugs were proposed. In the case of CF, IF and 5-FU the degradation process occurred mainly through ketonization, hydroxylation and dehalogenation, while MTX and IMB were decomposed by attack of hydroxyl radicals on benzyl position in parent compounds. An important part of the research was the evaluation of eco-toxicity of electrochemically treated drug solutions against Lemna minor. Toxicity of initial 5-FU and MTX solutions towards L. minor were observed but after electrochemical treatment its toxicity decreased. The opposite trend was observed for CF and IF. In this case no significant toxicity was observed for the initial solutions of these drugs, while after electrochemical treatment an increase in growth inhibition of L. minor was found.

Neutrophils contribute to the pathogenesis of hemorrhagic cystitis induced by ifosfamide

Ifosfamide (IFO) is an antineoplastic drug that is commonly used to treat gynecological and breast cancers. Hemorrhagic cystitis (HC) is a common side effect associated with IFO injection, which courses with neutrophil accumulation and affects 6–50% of patients depending on dose intensity. Here, we investigated the role of neutrophils in this inflammatory process. Female Swiss mice (n = 8/group) were injected with saline, IFO (400 mg/kg, i.p.), fucoidan (a P- and L-selectins inhibitor, 100 mg/kg, i.v.) or IFO + fucoidan (1–100 mg/kg) alone or combined with mesna (80 mg/kg i.p.). Another group of mice received anti-Ly6G antibody (500 μg/mouse, once daily for 2 days) for neutrophil depletion before IFO injection. In another experimental setting, animals received granulocyte colony-stimulating factor (G-CSF, 400 μg/kg), IFO (200 mg/kg), G-CSF (25–400 μg/kg, for 5 days) + IFO (200 mg/kg, i.p.) or fucoidan + G-CSF + IFO. Bladder injury was evaluated 12 h after IFO injection. IFO 400 mg/kg significantly increased visceral hyperalgesia, bladder edema, hemorrhage, vascular permeability, MPO, IL-1β and IL-6 tissue levels, and COX-2 immunostaining and expression versus the saline group (P < 0.05). Conversely, fucoidan (100 mg/kg) significantly attenuated these parameters compared to IFO-injected mice (P < 0.05). Additionally, fucoidan potentiated mesna protective effect when compared with IFO + mesna group (P < 0.05). Accordingly, neutrophil depletion with anti-Ly6G reduced inflammatory parameters and bladder injury compared to IFO (P < 0.05). In contrast, G-CSF enhanced IFO (200 mg/kg)-induced HC, which was significantly attenuated by treatment with fucoidan (P < 0.05). Therefore, neutrophils contribute to the pathogenesis of HC.

Alternative Chemotherapy Schedules in Ewing's Sarcoma: An Indian Perspective

AbstractAdvances in the treatment of Ewing's sarcoma family of tumors (ESFTs) are a result of improvements in systemic and local therapies. VACA (vincristine, Adriamycin [doxorubicin], cyclophosphamide, dactinomycin) chemotherapy alone versus VACA + IE (VACA with alternate ifosfamide, etoposide) improve survival, but this regimen cannot be given to all patients due to poor tolerance and 5-day schedule chemotherapy in VACA + IE schedule. We reviewed the records of 50 patients treated as per our institutional protocols from 2007 to 2011. Two schedules of chemotherapy followed were vincristine, Adriamycin, cyclophosphamide (VAC) and VAC with alternate ifosfamide, etoposide (VAC + IE). Factors predictive of local failure and distant recurrence were analyzed. A total of 50 patients were analyzed. The median age at diagnosis was 14 years. Thirty-two patients were male, whereas 18 were female. Approximately, 95% of the patients relapsed after a median time gap of 1.6 years. The median 5-year disease-free survival was 30%. Systemic treatment with VAC or VAC + IE–based chemotherapy had equal local control and distant control rates. Smaller tumors had a better local control and lesser systemic failure than those of larger sizes. Successful treatment of Ewing's sarcoma requires optimal systemic and local therapy. Both the chemotherapy regimens showed equal survival rates. Control of both the local and distant diseases is a result of the combined modality approach. Stage at presentation is the most important factor for prognosis. Complete surgery and local radiotherapy are important predictive factors for local and systemic control.

Single-agent expansion cohort of lenvatinib (LEN) and combination dose-finding cohort of LEN + etoposide (ETP) + ifosfamide (IFM) in patients (pts) aged 2 to ≤25 years with relapsed/refractory osteosarcoma (OS).

11527Background: LEN is a multikinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, KIT, and RET. In human pediatric OS xenograft models, LEN enhanced the antitumor activity of IFM + ETP. In a phase (Ph)...

Impact of 3-year survival rate on treating IIB limb osteosarcoma patients with methotrexate plus DIA chemotherapy regimen

Objecitve To evaluate the impact of adding methotrexate into DIA chemotherapy regimen (cisplatin, theraru-bicin and ifosfamide) on 3-year disease-free and overall survival of patients with IIB osteosarcoma in extremities. Methods Retro-spectively analyzed 34 cases of IIB limb osteosarcoma according to the Musculoskeletal Tumor Society (MSTS) surgical staging system with pathologically diagnosed concurrent chemotherapy and comprehensive surgical treatment from May 2008 to April 2014. There were 20 males and 14 females, with an average age of 19.5±7.7 years (ranged from 9 to 44 years). 28 patients underwent limb salvage surgery, and 6 patients received amputation. Tumor site included distal femur in 21 patients, proximal tibia in 9 patients, other sites in 4 patients. Seventeen patients underwent cisplatin, THP and ifosfamide (DIA) regimen of chemotherapy. The other 17 patients underwent cisplatin, THP, ifosfamide and methotrexate (MDIA) regimen. Patients charts were reviewed to get demographic data including age, gender, site, tumor size, surgery type, chemotherapy regimen, alkaline phosphatase, lactase dehydrogenase. The prognostic value of these factors on 3 years disease free survival and overall survival were calculated with Kaplan-Meier method and compared with Log-Rank test between different groups in univariate comparison and COX model for multivariate analysis was used to determine whether these demographic factors are independent prognostic factor for survival. Results Two patients had local recurrence, 7 patients had metastasis, and 2 patients had both local recurrence and metastasis. The 3-year survival of the whole group was 67.6% (23/34). Seven patients died during follow-up. The overall survival was 79.4% (27/34). The 3-year disease-free survival in DIA group and MDIA group was 70.6% (12/17) and 64.7% (11/17), respectively. The 3-year overall survival was 82.4% (14/17) and 76.5% (13/17) in DIA group and MDIA group, respectively. Univariate analysis showed that there was no significant difference in either 3-year disease-free survival (χ2=0.113, P=0.737) or overall survival (χ2=0.197, P=0.657) between DIA and MDIA. Age was significantly correlated with prognostic in univariate analysis (χ2=5.869, P=0.015), while gender, tumor site, tumor size, surgery type, ALP, LDH was not correlated with disease-free survival. Kaplan-meier analysis with Log-Rank test showed age (χ2=6.134, P=0.013) and tumor size (χ2=5.108, P=0.024) were statistically correlated with overall survival. Multivariate analysis with COX model showed that chemotherapy regimen was not an independent prognostic factor for 3-year disease-free survival or overall survival. Age was an independent prognostic factor for 3-year disease-free survival (HR=5.836, P=0.017). Conclusion The addition of MTX on the basis of DIA chemotherapy regimen did not significantly improve the 3-year disease-free survival and overall survival of stage IIB limb osteosarcoma. Key words: Osteosarcoma; Extremities; Antineoplastic combined chemotherapy protocols; Survival rate

Preliminary evaluation of the application of carbon nanotubes as potential adsorbents for the elimination of selected anticancer drugs from water matrices

The presence of anticancer drugs in the environment raises a major concern due to their potentially negative impact on living organisms, as they cause, inter alia, teratogenic, mutagenic, carcinogenic effects on growing cells. The main source of these pharmaceuticals in the environment is the ineffectively treated wastewaters, hence the efficient methods for their removal are required. In this study, we have evaluated for the first time the applicability of different Multi-Walled Carbon Nanotubes (MWCNTs) as alternative adsorbents for the removal of three popular anticancer drugs from water matrices, which are detected in waste/hospital waters at the concentrations even up to μg L−1: cyclophosphamide (CP), ifosfamide (IF) and 5-fluorouracil (5-FU). It was observed that adsorption equilibrium time was reached after 20 min for each compound and CNTs. Moreover, CP has the highest sorption potential (Kd up to 1597 L kg−1) for all CNTs and CNTs with the highest surface area have the greatest adsorption capacity. Isotherms were fitted best to the Freundlich model. Significant influence of pH in the range 4–9 and ionic strength was not observed what may indicate that adsorption is not dependent on fluctuation of basic environmental conditions.

Survival of children with relapsed medulloblastoma treating with high-dose chemotherapy and intrathecal Methotrexate: a retrospective study in a single institution

Objective To investigate the treatment value of intensified chemotherapy combined with intrathecal Methotrexate (ITMTX) in the treatment of children with relapsed medulloblastoma. Methods From February 2011 to February 2014, 40 relapsed patients in Beijing Shijitan Hospital, Capital Medical University, aged 10.6 years (2.7 to 17.7 years), were received 4 cycles of carboplatin and Etoposide continuously infusion for 96 h, and sequentially fo-llowed with Ifosfamide, Etoposide and Nedaplatin for 3 cycles, then administrated oral Temozolomide (TMZ) and Etoposide for 12 cycles.All patients were divided into ITMTX group, which were performed ITMTX during every chemotherapy or every 3 weeks, and no intrathecal Methotrexate (no-ITMTX) group, which were not performed with ITMTX.Responses were evaluated, and the objective response time, time to tumor progress (TTP), time to treatment failure (TTF), and recurrence-free interval (RFI) of the two groups were contrasted.The side-effects of chemotherapy and ITMTX were analyzed, overall survival was calculated using Kaplan-Meier method, and chi-square test or t test was used to compare the difference between two groups. Results Until 30th December 2016, the follow-up time was 29.4 months (ranging from 2 to 57 months). The 3-year overall survival (OS) rate was (53.5±8.1)%, and 45.0% patients were objective response, and the mean objective response time was 2 months, and the RFI was 18 months.For ITMTX patients, the 3-year OS rate was (66.6±11.5)%, the objective response ratio was 70.0%, and mean objective response time was 1.5 months, 24 months free-event of TTP and TTF was 70.0% and 90.0%, respectively, and the RFI was 22.5 months.For no-ITMTX patients, the 3-year OS rate was (40.0±11.0)%, objective response ratio was 20.0%, and mean objective response time was 2.5 months (1.5-4.0 months), 24 months free-event of TTP and TTF was 35.0% and 50.0%, respectively, and the RFI was 5 months (0-40 months). Compared with those of no-ITMTX patients, the RFI, 24 months TTP and TTF of ITMTX patients were much better, there were statistical signi-ficances (all P<0.05). The main side-effects of chemotherapy was gastrointestinal hematologic side-effects, and recovered quickly with supportive treatment.No obvious Methotrexate induced neurotoxicity was found. Conclusion Based on high-dose chemotherapy, ITMTX can further improve the long-term survival of patients with relapsed medulloblastoma, and it is more feasible and suitable for relapsed MB children in China. Key words: Medulloblastoma; Relapsed; Chemotherapy; Methotrexate; Child

Primitive neuroectodermal tumor (PNET) as somatic-type malignancy arising from an extragonadal germ-cell tumor: clinical, pathological and molecular features of a case.

We report a rare case of a 34-year-old man with a right axillary mass. Ten years previously, he had been diagnosed with a right scapular nonseminomatous germ-cell tumor consisting of teratoma, completely resected without any further treatment. Presently he was found to have a metastatic malignant small round cell tumor consistent with a secondary somatic malignancy arising in the background of nonseminomatous germ-cell tumor, teratoma, yolk sac tumor, and primitive neuroectodermal tumor with distinct chromosome 22 translocation. Although the patient initially responded well to chemotherapy with etoposide, cisplatin, ifosfamide and mesna, he relapsed shortly after.

Primary renal angiosarcoma: case report and review of world literature.

This article focuses on a rare case of primary renal angiosarcoma in a 56-year-old man with a previous clinical history of stage III Hodgkin's lymphoma treated with supra- and subdiaphragmatic radiotherapy, splenectomy in association with vincristine-based chemotherapy and thermochemotherapy, and subsequent thymectomy. The patient was referred to the department of urology from the department of cardiology, where he had been seen for right coronary stenosis after the incidental finding on an abdominal scan of a large left renal mass. There was no family history of renal cancer. Diagnosis was high-grade angiosarcoma, extensively necrotic and hemorrhagic, involving the renal parenchyma and perirenal soft tissue. Taking into account tumor histology, grade, size and site as well as patient's age and general condition, a therapeutic program was planned comprising surgery followed by chemotherapy (epirubicin 60 mg/m² and ifosfamide 3000 mg/m²). Adjuvant radiotherapy, normally delivered to the site of surgery, was not considered necessary. Unfortunately the patient died 4 months after surgery, before chemotherapy was started. Our paper highlights the extreme rarity and aggressiveness of renal sarcoma, its poor prognosis, and the fact that there is no one, accepted approach to its treatment.

Retroperitoneal surgery in the treatment of germ-cell tumors of the testis: retroperitoneal lymph node dissection (RPLND)

Germ-cell tumors of the testis (GCTT) are rare, but have a high social impact. In fact they represent no more than 1% of male tumors (about 700 new cases per year in Italy), but electively occur in young patients, 20 to 40 years old, during their fully mature social and working life. More than 80% of patients are cured and return to a normal social, sexual, and working life. Improvements achieved both in diagnosis, with the use of scans (CT, MRI, US and recently PET) and of serum tumor markers alpha-fetoprotein (AFP), beta-fraction of human chorionic gonadotropin (b-HCG) and lactate dehydrogenase (LDH), and mainly in treatment, through the amelioration of radiotherapy and surgical techniques and, especially, with the introduction of Cisplatin, Etoposide and Ifosfamide in chemotherapic regimens, have made germ-cell tumor a model of "curable disease". Retroperitoneal lymph node dissection (RPLND) has indications in patients with clinical stage I (CS1) as well as in advanced disease, where it is integrated in the multimodality treatment. Anatomical studies, as well as a long-term experience, have gradually but consistently modified the surgical techniques of RPLND. Currently, "nerve sparing" RPLND represents a safe management of CS1 nonseminomatous germ cell testicular tumor with minimal morbidity and excellent outcomes. Nonetheless, surveillance and adjuvant chemotherapy are as effective as RPLND, but, in our opinion, associated with some discomforts for the patients. Laparoscopic retroperitoneal lymph node dissection (Lap-RPLND) is gaining popularity as a minimally invasive staging procedure for clinical stage I nonseminomatous testicular carcinoma, but its therapeutic role is still under investigation.

Assessment of mutagenic and antimutagenic effects of Punica granatum against ifosfamide induced chromosomal aberrations in male albino mice

The present study has been done to assess the mutagenic and antimutagenic effects of Punica granatum (Pomegranate) seed extract against the genotoxic effects ifosfamide (IFO) in male albino mice Mus musculus of BALB/c strain. The pomegranate seed extract (tablets) was provided by Source naturals, INC. Santa Cruse Company, Canada (from Egypt). Two independent experiments were performed. In the first, mice was treated daily and orally with phosphate buffer saline (PBS) as negative control group, and the other three groups were treated daily and orally with three different doses of the P. granatum seed extract (12.5, 25, and 50 mg/kg b.w.) for five weeks in order to test the clastogenetic effects of the plant seed extract. In the second experiment, the first group was positive control group which weekly and intraperitonially was treated with ifosfamide (100 mg/kg b.w.), the other three groups were treated daily and orally with three different doses of the pomegranate seed extract (12.5, 25, and 50 mg/kg b.w.) and also intraperitonially treated at the end of each week with IFO for five weeks to test the protective effects P. granatum seed extract. The results of the first experiment indicated that the P. granatum seed extract has no significant clastogenetic effects on chromosomal aberrations of the bone marrow cells of treated mice. The results of the second experiment was that the P. granatum seed extract, especially at the third dose (50 mg/kg b.w.) exhibited well protective and anti-clastogenetic effect against the genotoxic actions of the ifosfamide on bone marrow cells

Total Claviculectomy as Treatment of Clavicular Ewing's Sarcoma: a Case Report and Literature Review

Objective To analyze the efficacy of total claviculectomy in the treatment of Ewing's sarcoma and to discuss the impact of clavicular reconstruction on the outcome. Methods The clinical records of a 13-year-old male patient with left clavicular Ewing's sarcoma were reviewed. The subject received 2 cycles (at an interval of 2 weeks) of neoadjuvant chemotherapy comprising cisplatin 120 mg/m2 (1 d), adriomycin 30 mg/m2 (3 d), and ifosfamide 2.0 g/m2 (5 d). Total claviculectomy was carried out without clavicular reconstruction and the patient underwent 9 cycles of subsequent chemotherapy. The appearance and function of the operated limb, radiological examinations of the surgical site, ECT bone scans and pulmonary CT were followed up. The literatures regarding the total and subtotal excision of the clavicle were reviewed to investigate the importance of clavicular reconstruction. Results After 23-months of follow-up, the patient was subjectively free of limb function compromise. Physical examinations indicated drooping of the operated shoulder by 2 cm, whereas the appearance was similar between both shoulders. Functionality of the operated limb was recovered. The motion of the left shoulder: abduction 90°, adduction 40°, anterior flexion 90°, extension 45°, internal rotation 80°, external rotation 60°, and no restriction of limb elevation. Manual muscle strength tests showed V/V muscle strength of the operated limb. American Shoulder and Elbow Surgeons' form (ASES) and Musculoskeletal Tumor Society (MSTS) score were 96 and 30, respectively. Postoperative X-ray films demonstrated mild thoracic scoliosis. The patient did not appear recurrence and metastasis. Conclusion Total claviculectomy is efficacious for treating clavicular Ewing's sarcoma. Clavicular reconstruction may not be imperative for treatment of clavicular malignancy because of the increased technical difficulty and great risk of complications. Key words: Sarcoma, Ewing; Clavicle; Surgical procedures; Bone remodeling; Recovery of function

Stropharia rugosoannulata and Gymnopilus luteofolius: Promising fungal species for pharmaceutical biodegradation in contaminated water

Pharmaceuticals are environmental micropollutants that pose an emerging challenge because they are poorly eliminated in conventional wastewater treatment plants. Over the last decade, many attempts have been made to solve this problem, and wastewater fungal treatment is a promising alternative. In this study, six different ligninolytic fungi (Trametes versicolor, Ganoderma lucidum, Irpex lacteus, Stropharia rugosoannulata, Gymnopilus luteofolius and Agrocybe erebia) were studied as bioremediation candidates for the removal and degradation of six recalcitrant pharmaceutical micropollutants: Carbamazepine (CBZ), Venlafaxine (VFX), Iopromide (IPD), Diclofenac (DCF), Cyclophosphamide (CFD) and Ifosfamide (IFD). Self-immobilization in a pellet shape was achieved for all fungal mycelia (which was the first time that this was reported for S. rugosoannulata, G. luteofolius, and A. erebia). Biodegradation achievement was greater than 90% for IPD with G. luteofolius and greater than 70% for CBZ with S. rugosoannulata, which suggests a great potential for this alternative biological treatment. Besides, this was the first report where fungal treatment achieved CFD and IFD removals greater than 20% for the treatment with T. versicolor, G. lucidum and S. rugosoannulata.

Evaluation of acute and chronic ecotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and UV treated samples

Cyclophosphamide (CP) and Ifosfamide (IF) are two nitrogen mustard drugs widely prescribed in cancer therapy. They are continuously released via excreta into hospital and urban wastewaters reaching wastewater treatment plants. Although CP and IF, their metabolites and transformation products (TPs) residues have been found in the aquatic environment from few ng L-1 to tens of μg L-1, their environmental toxic effects are still not well known. The present study aimed to investigate the acute and chronic ecotoxicity of CP and IF and their commercially available human metabolites/TPs, i.e. carboxy-CP, Keto-CP and N-dechloroethyl-CP on different organisms of the aquatic trophic chain. The experiments were performed using the green alga Pseudokirchneriella subcapitata, the rotifer Brachionus calyciflorus and the crustaceans Thamnocephalus platyurus and Ceriodaphnia dubia. Moreover, to assess the treatment conditions in regards to parent compound removal and formation of new TPs, CP and IF were UV- irradiated for 6h, 12h, 24h, 36h and 48h, followed by toxicity evaluation of treated samples by algae, rotifers and crustaceans. Between the parent compounds, IF resulted as more toxic drug under tested conditions, exerting both acute and chronic effects especially on C.dubia (LC50:196.4mgL-1, EC50:15.84mgL-1). Among the tested metabolites/TPs, only carboxy-CP inhibited the reproduction in the rotifer. However, LOEC and NOEC values were calculated for CP and IF for all organisms. In addition, despite a low degradation of CP (28%) and IF (36%) after 48h UV-irradiation, statistically significant effect differences (p<0.05) from not-irradiated and irradiated samples were observed in both acute and chronic assays, starting from 6h UV-irradiation. Our results suggest that the toxic effects found in the aquatic organisms may be attributable to interactions between the parent compounds and their metabolites/TPs.

Prognostic value of interim 18F-FDG PET/CT in patients with natural killer/T cell lymphoma

Objective To investigate the prognostic value of interim 18F-FDG PET/CT scan in patients with natural killer (NK)/T cell lymphoma. Methods From January 2012 to May 2015, thirteen patients (10 males, 3 females; mean age (43.85±7.66) years) underwent methotrexate+ ifosfamide+ etoposide+ prednisone acetate+ L-asparaginase (SMILE) chemotherapy. All patients underwent pre-, mid-treatment (after 3 cycles of SMILE) PET/CT scan, and 9 of them further underwent end-treatment (after 6 cycles of SMILE) PET/CT scan.View analysis and ΔSUVmax(%) were used to interpret 18F-FDG PET/CT images. Two-sample t test was used to analyze the difference of ΔSUVmax between PET/CT positive group and PET/CT-negative group. Survival curves were obtained using Kaplan-Meier analysis. OS and PFS were calculated and compared with the log-rank test. Results All 13 patients underwent 18F-FDG PET/CT imaging after 3 chemotherapy cycles and were divided into PET/CT-negative group (7 patients) and positive group (6 patients). ΔSUVmax of the negative group was higher than that of the positive group: (65.73±5.95)% vs (52.50±1.49)%; t=4.199, P<0.05. Median follow-up period was 26 (9-48) months. The median PFS and median OS of PET/CT-negative group were higher than those of PET/CT-positive group (39 vs 18 months, 44 vs 24 months; χ2=4.521, 4.829, both P<0.05). Conclusion Interim PET/CT scan could predict the outcome of patients with NK/T cell lymphoma. Key words: Lymphoma, T-cell; Prognosis; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Brentuximab for Refactory Hodgkin’s Lymphoma: A Case Report

Hodgkin's lymphoma (HL) continues to be an intriguing, and fascinating lymphoma [1]. HL is expected to cure the majority of patients. Brentuximab vedotin is a CD30 antibody. We survey efficacy of brentuximab in patient with HL who was resistant to treatment. A 43 year old male referred with cough and right supraclavicular lymphadenopathy. His disease was HL, nodular sclerosis type (stage IIB and grade II) with megakaryocytosis in bone marrow aspiration (BMB). He was treated with 6 cycles of induction chemotherapy including adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) and achieved a complete remission by imaging assessment. Then he received ifosfamide, carboplatin, etoposide (ICE) plus brentuximab vedotin (1.8 mg/kg every 3 weeks) regimen for 6 courses. At the end of this time he been eligible for autologous bone marrow transplantation (BMT). Bone marrow was done and after 13 days with good engraftment the patient discharge hospital. Therapists should be try with a specific target when they need a new and potent treatment like BMT for an active disease. Brentuximab vendotin is a new drug in policy of recurrence that it used for a few of cases in Iran.