Injection Of 5-fluorouracil Research Articles

Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments

To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma. From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) and 24 retinoblastomas with partial remission/relapse TNM 7th Edition 1b (n = 13), 2a (n = 1) and 2b (n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6-27 months in 28 patients (30 eyes). Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal (n = 112) or external (n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy (n = 2), ptosis (n = 1) and strabismus/exotropia (n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7/16 (43%) newly diagnosed retinoblastomas and 1/22 (4.5%) retinoblastomas undergoing partial remission/relapse. For all treated eyes, Kaplan-Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3-97.5%), 74.4% (95% CI, 57-91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission/relapse, and eyes at presentation, K-M at 2 years were 95.5% (95% CI, 86.9-100%) and 45.6% (95% CI, 16.6-74.6%), respectively. Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents.

Keloids: current prophylactic and therapeutic methods

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Bienias W, Kaszuba A. Review paperKeloids: current prophylactic and therapeutic methods. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2012;29(6):446-450. doi:10.5114/pdia.2012.32392. APA Bienias, W., & Kaszuba, A. (2012). Review paperKeloids: current prophylactic and therapeutic methods. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 29(6), 446-450. https://doi.org/10.5114/pdia.2012.32392 Chicago Bienias, Wojciech, and Andrzej Kaszuba. 2012. "Review paperKeloids: current prophylactic and therapeutic methods". Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii 29 (6): 446-450. doi:10.5114/pdia.2012.32392. Harvard Bienias, W., and Kaszuba, A. (2012). Review paperKeloids: current prophylactic and therapeutic methods. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 29(6), pp.446-450. https://doi.org/10.5114/pdia.2012.32392 MLA Bienias, Wojciech et al. "Review paperKeloids: current prophylactic and therapeutic methods." Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, vol. 29, no. 6, 2012, pp. 446-450. doi:10.5114/pdia.2012.32392. Vancouver Bienias W, Kaszuba A. Review paperKeloids: current prophylactic and therapeutic methods. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2012;29(6):446-450. doi:10.5114/pdia.2012.32392.

Effectiveness of Needling Revision with Mitomycin-C for Failing Blebs

This surgical technique study was designed to evaluate the efficacy of surgical needling revision using Mitomycin-C to restore filtering function in scarred or encapsulated filtering blebs, and thereby minimize reliance on adjunctive medications. Twenty-eight eyes of 23 consecutive patients were studied, all having undergone operating room based bleb revisions for inadequate IOP-control during 2008-10. The standard needling procedure was performed as described with our previous data set, now using a 1-minute intra-bleb cannulation of 0.6 ml of 0.4 mg/ml MMC rather than multiple postoperative subconjunctival 5-fluorouracil injections. Outcome measures were IOP, number of antiglaucoma medications, and acuity. Both mean IOP reduction and decrease in anti-glaucoma medications at all four measured time intervals (1 week, 1 month, 2 months, 6 months) post-operatively were highly significant (p<0.0001). IOP was reduced from a mean of 27.2 ± 10.6 mmHg pre-op to 15 ± 7.8 mmHg 6 months post-op (Δ -45%), with 86% of eyes requiring glaucoma medication prior to the procedure and only 16% thereafter. At six months, 60% of eyes had IOP ≤15 mmHg without medications, and 76% ≤18 mmHg. Visual acuity was stable or improved in 69% of cases. Mitomycin-C augmented needling revision appears to be a reasonably safe and reliable option for restoring bleb function in glaucomatous eyes with failed filters.

Cicatricial Canthal Webs

Cicatricial canthal webs present a complex reconstructive challenge for the eyelid surgeon. A combination of vertical skin deficiency, cutaneous and subcutaneous scar, and altered anatomy and blood supply can make surgical correction difficult and unpredictable. Patients typically are seen after blepharoplasty surgery or trauma with both cosmetic and functional (visual-field obstruction in lateral gaze) deficits. This is often a significant frustration to both the patient and the surgeon. A combination of a Y-to-V advancement flap, adjacent tissue rearrangement with Z-plasties centered on the arms of the Y (five-flap technique), and scar excision, when necessary, can be a useful procedure for revision of these webs. The charts of patients who underwent cicatricial canthal web revision in the solo private practice of the author over a 5-year period (2006-2010) were retrospectively reviewed. Each patient had a history of previous eyelid surgery or trauma that led to the development of the web. No patient had previous surgery to address the web. Each patient's presenting complaints were aesthetic, functional, or both, and each was previously told to avoid revision, as surgery to correct the web would make the condition worse. Patient's pre- and postrevision digital photographs, and patient and physician assessments, were reviewed to evaluate the results of surgery. Postoperative injections of subcutaneous steroid (Kenalog) and/or 5-fluorouracil (5-FU) were given as a treatment adjunct to modulate wound healing and prevent scarring when deemed appropriate. Eight patients were included in the study. Seven (88%) patients are women, and 1 (12%) patient is a man. The mean patient age is 46 years (range, 18-56 years), and the mean follow-up is 17 months (range, 9-30 months). Seven (88%) of the patients had lateral canthal webs after surgery, and 1 (12%) patient had a medial canthal web after a motor vehicle accident. Every patient voiced aesthetic concerns with the web, and 4 (57%) of the 7 patients with lateral canthal webs reported a visual deficit related to the defect. Six (75%) patients received 3 separate injections of Kenalog postoperatively, and 2 (25%) patients received the same number of injections composed primarily of 5-FU admixed with steroid. Each patient was satisfied with the aesthetic and functional result of surgery. Cicatricial canthal webs are an uncommonly reported finding that has received little attention in the literature. The condition has both aesthetic and functional implications, can be very bothersome and frustrating to patients, and can be intimidating to the treating surgeon. Although surgical revision carries risks of flap necrosis, scar, and worsened appearance, it can also significantly improve appearance and function. If the patient is realistic, understands the limitation of surgery, and will be happy with a moderate improvement, surgery should be strongly considered. The author found that revision of cicatricial canthal webs with the technique described in this article yields excellent results, given the limitations of the presenting problem.

Subcutaneous injection containing IL-3 and GM-CSF ameliorates stab wound-induced brain injury in rats

Macrophage-like cells densely accumulate in stab wound-induced brain lesions in rats. Many of these cells express the macrophage marker Iba1 and the oligodendrocyte progenitor cell marker NG2 chondroitin sulfate proteoglycan (NG2), and have been termed BINCs (brain Iba1 +/NG2 + cells). Results from our previous study showed that BINCs elicit neuroprotective action, and agents inducing BINC activation or proliferation are expected to ameliorate traumatic brain injuries (TBIs). In the present study, TBI was established by inserting a needle into the cerebrum and moving the needle in a longitudinal, fan-like movement. Isolated BINCs from these stab lesions expressed mRNAs encoding receptors for interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF). When this mixture of cytokines was added to the cultured BINCs, expression of mRNAs encoding insulin-like growth factor-1, hepatocyte growth factor, and proliferating cell nuclear antigen increased. The cytokine mixture induced enhanced wound healing in BINCs-brain cell co-cultures in vitro. Stab wounds in the rats resulted in significant brain tissue loss at 2 months post-lesion. However, tissue loss was reduced by 40% when the combination of IL-3 and GM-CSF was subcutaneously injected 7 times (once per day) beginning at 2 or 3 days post-lesion (dpl). BINCs are highly proliferative and an intraperitoneal injection of 5-fluorouracil (5FU) at 2 dpl eliminated the BINCs, resulting in death of the rats. The cytokine mixture injection significantly reduced mortality of the 5FU-treated rats. These results suggest that the combination of IL-3 and GM-CSF serves as a promising agent to ameliorate TBI via action on BINCs.

Abstract LB-456: The intraductal injection of 5-fluorouracil induces immune response to eradicate and prevent breast cancer

Abstract Chemotherapy has been shown to act as an immune response modifier. Many groups, incuding our own, are using chemotherapy to induce immune responses such as by using low doses of cyclophosphamide. Our previous work has demonstrated that anti-cancer agents can eliminate new/existing tumors with minimal toxicity in rat and mouse models of breast cancer. Here we demonstrate that intraductal (i.duc), but not the intravenous (IV) route of injection, of chemotherapy to mammary glands alters the tumor environment to effectively induce immune effector cells. We used the mouse HER2/neu (neu/N) transgenic, spontaneous mammary tumor model. 5-fluorouracil (5FU) was administered intraductally to the mammary glands on the left side of parous mice whereas the mammary glands on right side received no treatment (NT). The mammary tumor incidence in the 5FU treated side was significantly lower compared to mice that received NT, and IV treated group. Interestingly the incidence of mammary tumors in the untreated side of 5FU-treated mice was also significantly lower compared to the NT and IV group. We hypothesized that the protection afforded to the contralateral chain of mammary glands by ipsilateral i.duc administration of 5FU, may be mediated through an immunological mechanism. Twenty week parous mice were administered 5FU either through i.duc injection, only to left side teats, IV injection, or NT. The mice received 5FU 2 times in a 4 week interval. A week after the second treatment, the mice were sacrificed and the regional lymphnodes (RLN) of the 3rd and 4th mammary glands and spleen were removed. We isolated lymphocyte from RLN and spleen to analyze by flowcytometry. The number of CD8 T cell showed no change among the groups in the RLN but was significantly lower in the i.duc group in the spleen. The number of CD62LLOW+ T cell in 5FU treated side of RLN was significantly higher compared to the IV and NT group. On the other hand the number of CD62LLOW+ was low in the spleen. To study the population of systemic memory T cell in the peripheral blood, blood was harvested into Trucount tubes and analyzed with memory T cells surface marker. Twenty week parous mice was administered 5FU i.duc injection only to the left side, IV injection, or NT every 4weeks for a total of 3 times. Cancer cells were injected into the left side of 4th mammary gland fat pad of the mice at 16 weeks after initial procedure. One hundred μl blood was collected 5 days before and 5 days after cancer cell injection. The mice treated by i.duc 5FU showed increased numbers of CD95+/CD62L low effector memory T (TEM) cells, whereas the mice treated with IV 5FU did not recruit TEM cells significantly. There was no significant change in CD95+/CD62L high central memory T cells before and after treatment and among the groups. In summary, i.duc administration of 5FU into mammary glands effectively induced immune effector cells and prevented mammary tumor growth in neu/N transgenic mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-456. doi:10.1158/1538-7445.AM2011-LB-456

Combined trabeculotomy-trabeculectomy augmented with 5-fluorouracil in paediatric glaucoma

To describe our experience of combined trabeculotomy-trabeculectomy in paediatric glaucomas with a special emphasis on the use of 5-fluorouracil and releasable sutures. Retrospective review carried out at Manchester Royal Eye Hospital, UK, a tertiary referral centre. Twenty-nine eyes of 21 consecutive patients with congenital glaucoma undergoing combined trabeculotomy-trabeculectomy augmented with 5-fluorouracil. 5-Fluorouracil augmented combined trabeculotomy-trabeculectomy was carried out with intense postoperative management and suture adjustment of releasable sutures within the first 3 weeks after surgery. Peribleb 5-fluorouracil injections were given repeatedly if there were signs of aggressive bleb scarring. Absolute success was defined as intraocular pressure of 21 mmHg or less, clear cornea and absence of progressive glaucomatous optic disc changes at last follow up, whereas qualified success was defined as these endpoints with anti-glaucoma medication. Absolute success was achieved in 19 out of 29 eyes (65.5%), and a further 4 (13.8%) had qualified success. There was no difference in the surgical outcomes of primary infantile glaucoma and secondary causes of paediatric glaucoma such as anterior segment dysgenesis. Combined trabeculotomy-trabeculectomy had a significantly greater success rate as a secondary procedure rather than as a primary procedure. 5-Fluorouracil-enhanced combined trabeculotomy-trabeculectomy with releasable sutures appears to be an effective procedure for congenital glaucoma refractory to goniotomy. It is less effective as a primary procedure when severe corneal haze prevents goniotomy in newborn congenital glaucoma. Intense postoperative monitoring including active bleb manipulation with needling and 5-fluorouracil injections may increase the success of the procedure.

Therapeutic effect of microwave ablation combined with injection of 5-fluorouracil in mice bearing CT26 colon carcinoma xenografts

Therapeutic effect of microwave ablation combined with injection of 5-fluorouracil in mice bearing CT26 colon carcinoma xenografts

Effects of Bolus Injection of 5-Fluorouracil on Steady-State Plasma Concentrations of 5-Fluorouracil in Japanese Patients with Advanced Colorectal Cancer

The irinotecan (CPT-11) + 5-fluorouracil (5-FU)/leucovorin (LV) + UFT/LV chemotherapy, in which repetitive oral administration of UFT/LV replaces the infusion of 5-FU/LV in the FOLFIRI regimen, has been proposed previously. In this study, five of 10 patients were injected with a bolus of 5-FU and the other were not injected with it in order to examine the effect of omitting it in terms of pharmacokinetics of 5-FU. The treatment consisted of the intravenous infusions of CPT-11 at 100 mg/m(2 )and l-LV at 15 mg/m(2), and the injection of a bolus of 5-FU at 500 mg/m(2) on day 1, and the repetitive oral administration of UFT/LV (300 mg/m(2)/day as tegafur + 75 mg/day of LV) on days 1-5. A total of 13 measurements of the plasma concentrations of uracil, 5-FU and tegafur were made per patient within 48 hr after the start of chemotherapy and the value of area under the concentration-time curve (AUC(0-48)) was evaluated. The plasma concentration was also determined at 2 weeks to assess long-term exposure to 5-FU. The plasma concentrations of 5-FU at 24 hr after the start of treatment were 27.4 ng/mL and 9.4 ng/mL in the patients with and without the bolus injection, respectively. At 48 hr, they were 31.3 ng/mL and 10.4 ng/mL with the AUC(0-48) values of 22.16 mg h/L and 0.65 mg h/L, respectively. The 5-FU was detected in the plasma at 226 hr after the last administration of UFT/LV for the patients with the bolus injection, but not for those without. A bolus of 5-FU on day 1 provided long-term exposure to 5-FU.

Low-dose 5-fluorouracil induces cell cycle G2 arrest and apoptosis in keloid fibroblasts

Intralesional injection of low-dose 5-fluorouracil (5-FU) has recently been used as an experimental modality for treating keloid scarring and has shown promising efficacy in improving scar appearance and preventing recurrence of the keloid. We sought to explore the cellular- and molecular-based evidence for the observed clinical benefits. Primary cell lines of keloid fibroblasts were treated with 5-FU at a range of lower doses (∼10 mg mL(-1) ) in monolayer culture and subjected to examination for cell viability, proliferative potential, apoptosis, cell cycle and associated proteins involved in cell cycle control. 5-FU significantly inhibited cell proliferation of keloid fibroblasts in the full dose range used in this study. The DNA synthesis was completely inhibited by 5-FU at 72 h, and significant cell apoptosis was observed at concentrations ≥ 1 mg mL(-1) for a period over 72 h. 5-FU caused a significant delay in cell cycle progression and the G2/M phase arrest. 5-FU induced p53 and p21 accumulation together with a decrease in cyclin B1 and Bcl-2 levels in treated keloid fibroblasts. Our data indicate that low-dose 5-FU (as low as 1 mg mL(-1) ) induces significant inhibition of proliferation, G2/M cell cycle arrest and apoptosis but not immediate cell death of keloid fibroblasts. The lack of tissue necrosis is a particular benefit as further scarring is likely to be prevented. These results support the use of low-dose 5-FU as a potential modality for treating keloid scars.

Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study)

Fluorouracil and folinic acid with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) are widely used as first-line or second-line chemotherapy for metastatic colorectal cancer. However, infusional fluorouracil-based regimens, requiring continuous infusion and implantation of an intravenous port system, are inconvenient. We therefore planned an open-label randomised controlled trial to verify the non-inferiority of irinotecan plus oral S-1 (a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate; IRIS) to FOLFIRI as second-line chemotherapy for metastatic colorectal cancer. Between Jan 30, 2006, and Jan 29, 2008, 426 patients with metastatic colorectal cancer needing second-line chemotherapy from 40 institutions in Japan were randomly assigned by a computer-based minimisation method to receive either FOLFIRI (n=213) or IRIS (n=213). In the FOLFIRI group, patients received folinic acid (200 mg/m(2)) and irinotecan (150 mg/m(2)) and then a bolus injection of fluorouracil (400 mg/m(2)) on day 1 and a continuous infusion of fluorouracil (2400 mg/m(2)) over 46 h, repeated every 2 weeks. In the IRIS group, patients received irinotecan (125 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was progression-free survival, with a non-inferiority margin of 1.333. Statistical analysis was on the basis of initially randomised participants. This study is registered with ClinicalTrials.gov, number NCT00284258. All randomised patients were included in the primary analysis. After a median follow-up of 12.9 months (IQR 11.5-18.2), median progression-free survival was 5.1 months in the FOLFIRI group and 5.8 months in the IRIS group (hazard ratio 1.077, 95% CI 0.879-1.319, non-inferiority test p=0.039). The most common grade three or four adverse drug reactions were neutropenia (110 [52.1%] of 211 patients in the FOLFIRI group and 76 [36.2%] of 210 patients in the IRIS group; p=0.0012), leucopenia (33 [15.6%] in the FOLFIRI group and 38 [18.1%] in the IRIS group; p=0.5178), and diarrhoea (ten [4.7%] in the FOLFIRI group and 43 [20.5%] in the IRIS group; p<0.0001). One treatment-related death from hypotension due to shock was reported in the FOLFIRI group within 28 days after the end of treatment; no treatment-related deaths were reported in the IRIS group. Progression-free survival with IRIS is not inferior to that with FOLFIRI in patients receiving second-line chemotherapy for metastatic colorectal cancer. Treatment with IRIS could be an additional therapeutic option for second-line chemotherapy in metastatic colorectal cancer. Taiho Pharmaceutical Co Ltd and Daiichi Sankyo Co Ltd.

Chemotherapy-induced myelotoxicity and incidence of lung metastasis in an animal model

We examined how chemotherapy-induced myelotoxicity and the associated leukopaenia affect cancer metastasis in an animal model. Myelotoxicity was induced by a single injection of 5-fluorouracil (5-FU) or Cisplatin, administered to 7-week-old BALB/c mice. CT-26 murine colon carcinoma cells were injected into the lateral tail vein on days 0, 1, 3, 5, and 7 after anticancer drug injection. On day 14 after cancer cell injection, the number of pulmonary colonies was measured in a double-blind setting. Compared with Cisplatin, 5-FU induced severe leukopaenia and bone marrow suppression, while on day 5, both drugs induced severe myelotoxicity. The number of pulmonary colonies did not correlate with the severity of leukopaenia, regardless of the type or time of drug injection, except in the group pretreated with Cisplatin (3 days prior to cancer cell injection). Our results suggest that chemotherapy-induced myelotoxicity does not increase the incidence of cancer metastasis in this animal model.

Short-Term Effects of Subconjunctival Injections of 5-Fluorouracil on Conjunctival Epithelium

To assess the changes in the conjunctival cytology of patients given a subconjunctival injection of 5-fluorouracil (5-FU) to treat failed filtering blebs. The patients were classified into 3 groups. The first group included 15 eyes in 15 patients who were given subconjunctival injections of 5-FU after unsuccessful glaucoma surgery. The second group consisted of 15 eyes of 15 patients with primary open angle glaucoma treated with antiglaucomatous eyedrops. Twelve healthy age- and sex-matched volunteers formed the third group. Impression cytology specimens were obtained from the bulbar conjunctiva just beside the injection sites using cellulose acetate filter paper. The samples were fixed in 95% ethanol, stained with Papanicolaou stain, and evaluated under light microscopy and graded. In the first group, grade 0-3 cytological changes were seen in 1 eye (6.6%), 9 eyes (60%), 4 eyes (26.6%), and 1 eye (6.6%). Apoptosis was observed in 2 eyes (13%) and nuclear atypia in 7 eyes (47%). In the second group, 9 eyes (60%) were grade 0, 4 eyes (27%) were grade 1, and 2 eyes (13%) were grade 2. Also, nuclear atypia was observed in 1 eye (6.6%). In the third group, 10 eyes (83%) were grade 0 and 2 eyes (17%) were grade 1. There was no significant difference in terms of the impression cytology grades between the groups because of small sample size. The use of subconjunctival 5-FU injections after glaucoma surgery may lead to squamous metaplastic changes and nuclear atypia and apoptotic cell death in the conjunctival epithelium in short-term period.

The efficacy and safety of bufadienolides-loaded nanostructured lipid carriers

Bufadienolides-loaded nanostructured lipid carriers (BU-NLC) were prepared for parenteral application using glyceryl monostearate as solid core, medium-chain triglyceride and oleic acid as liquid lipid material, and Lipoid E-80 ®, sodium deoxycholate and pluronic F68 as stabilizers. In this study, the in vitro cytotoxicity, pharmacokinetics, biodistribution, antitumor efficacy and safety of BU-NLC were evaluated. Against human astrocytoma cell line (U87-MG) and human gastric carcinoma cell line (HGC-27) BU-NLC exhibited cytotoxicity that was similar to that of the free drug, and superior to that of the commercially available fluorouracil injection. BU-NLC exhibited a linear pharmacokinetic behavior at doses ranging from 0.25 to 1.0 mg/kg. The improved pharmacokinetic profile of bufadienolides when formulated in BU-NLC resulted in a higher plasma concentration and lower clearance after intravenous administration compared with bufadienolides solution (BU-S). A biodistribution study indicated that bufadienolides were mainly distributed in the lung, spleen, brain and kidney, and the longest retention was observed in the brain. A sarcoma-180 tumor model further confirmed the advantages of BU-NLC versus BU-S. Hemolysis and acute toxicity investigations showed that BU-NLC was safe when given by intravenous injection with reduced toxicity. In conclusion, the NLC system is a promising approach for the intravenous delivery of bufadienolides.

Orally administered emu oil decreases acute inflammation and alters selected small intestinal parameters in a rat model of mucositis

Mucositis resulting from cancer chemotherapy is a serious disorder of the alimentary tract. Emu oil has demonstrated anti-inflammatory properties in animal models of arthritis and wound healing; however, its effects on the intestine remain unknown. We investigated emu oil for its potential to decrease the severity of mucositis in a rat model. Female Dark Agouti rats (110-150 g) were orogastrically gavaged with emu oil (0.5 or 1 ml) or water (1 ml) for 5 d before intraperitoneal injection of 5-fluorouracil (5-FU, 150 mg/kg) or saline (control), and this was continued up to the day of sacrifice (48, 72 and 96 h post 5-FU administration). Histological (villus height, crypt depth (CD) and disease severity score) and biochemical (myeloperoxidase (MPO) activity) parameters were determined in intestinal tissues collected at sacrifice. Sucrase activity in vivo was quantified by the sucrose breath test. Activated neutrophil activity (MPO) in the ileum was significantly decreased by emu oil (0.5 ml, 451 (sem 168) U/g and 1 ml, 503 (sem 213) U/g) compared with 5-FU-treated controls (1724 (sem 431) U/g) 96 h post 5-FU administration. There were also significant increases in CD (152 (sem 8) microm) in the ileum of rats that received 1 ml emu oil at 96 h compared with 5-FU-treated controls (CD (106 (sem 12) microm)). Emu oil did not affect sucrase activity. Emu oil decreased acute ileal inflammation, and improved mucosal architecture in the intestine during recovery from chemotherapy in rats. Further studies investigating the potential benefits of emu oil as a nutritional supplement for the treatment of intestinal disorders are indicated.

A phase II trial of docetaxel plus nedaplatin and 5-fluorouracil in treating advanced esophageal carcinoma

Accumulating data indicate that docetaxel plus cisplatin and 5-fluorouracil has certain effect on advanced gastric or gastro-oesophageal junction adenocarcinoma. This study was to evaluate the efficacy and toxicity of docetaxel plus nedaplatin and 5-fluorouracil (DNF regimen) in treating advanced esophageal carcinoma. Forty-three patients with pathologically confirmed advanced esophageal carcinoma treated by DNF regimen: intravenous infusion of docetaxel (75 mg/m(2)) over 1 h, intravenous infusion of nedaplatin (100 mg/m(2)) over 3 h, intravenous infusion of leucovorin (CF, 200 mg/m(2)) over 2 h, intravenous injection of 5-fluorouracil (375 mg/m(2)) over 10 min, followed by a 46-hour infusion of 5-fluorouracil (2.6 g/m(2)). The cycle was repeated every three weeks. Treatment efficacy was evaluated every two weeks according to the WHO standards. All patients received at least two cycles of chemotherapy. Patients received a total of 144 cycles of treatment, and all were evaluable for efficacy and toxicity. Of the 43 patients, 2 (4.65%) achieved complete response (CR), 25 (58.14%) achieved partial response (PR), 9 (20.93%) had stable disease (SD), and 7 (16.28%) had progressive disease (PD). The overall response rate was 62.8%. The median time-to-progression (TTP) was 201 days and the median survival time (MST) was 310 days. Grade III/IV adverse events mainly included neutropenia (20.93%), febrile neutropenia (4.65%), thrombocytopenia (6.98%) and vomiting (9.30%). One patient died of grade IV thrombocytopenia. DNF regimen is effective for and well tolerated by patients with advanced esophageal carcinoma.

Use of 5-Fluorouracil Injections to Reduce the Risk of Trabeculectomy Bleb Failure After Cataract Surgery

To determine whether the use of postoperative subconjunctival 5-fluorouracil (5-FU) reduces the risk of trabeculectomy bleb failure after uncomplicated small incisional cataract surgery. Twenty-five consecutive patients with primary open-angle glaucoma and a functioning trabeculectomy bleb and who underwent uncomplicated phacoemulsification surgery were given subconjunctival injections of 5 mg 5-FU at 2, 4, and 12 weeks after cataract surgery (5-FU group). The mean postoperative intraocular pressure (IOP) over a 2-year period and the trabeculectomy survival rate, as determined by Kaplan-Meier survival analysis, was compared with a historical series of patients who had undergone cataract surgery in the presence of a filtering trabeculectomy bleb, but who had not received 5-FU (control group). After a 2-year follow-up period, there was no significant difference in the mean IOP between the 5-FU (15.1 mm Hg SD 3.1) and control (15.3 mm Hg SD 3.3) groups (P = 0.67). An IOP > 21 mm Hg at any time point after the first postoperative month after cataract surgery was found in 4.0% cases in the 5-FU group and 16.7% cases in the control group (P = 0.78). Using Kaplan-Meier survival analysis, the difference in the cumulative probability of survival between the 5-FU and control groups was not significant (P = 0.30). Cataract surgery is a significant risk factor for trabeculectomy bleb failure. The use of subconjunctival 5-FU injections at 2, 4, and 12 weeks after cataract surgery in elderly white patients with primary open-angle glaucoma does not reduce the risk of trabeculectomy failure.

Endoscopic Chemotherapy with 5-Fluorouracil in Advanced Gastric Cancer

It has been reported that a local injection of 5-fluorouracil (5-FU) administered endoscopically can have a favorable result in patients with early gastric cancer. We report the application of a local injection of 5-FU administered endoscopically in three patients with advanced gastric cancer (AGC) who refused or were not suitable for surgery or systemic chemotherapy. The benefits of locally applied endoscopic chemotherapy (EC) with 5-FU as an alternative therapy were evaluated. Good tolerance with an important reduction of the tumor size and no adverse reactions was observed in all three patients. EC with 5-FU is a feasible technique that can be applied in a certain group of patients with AGC. Further studies will be required to corroborate these results.

Iba1+/NG2+ Macrophage-Like Cells Expressing a Variety of Neuroprotective Factors Ameliorate Ischemic Damage of the Brain

In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore, the cells were termed BINCs (Brain Iba1(+)/NG2(+) Cells). A bone marrow transplantation experiment using green-fluorescent protein-transgenic rats showed that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2 days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level. Immunohistochemical staining showed that IGF-1-expressing BINCs were found not only in rat but also human ischemic brain lesions. These results suggest that bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors.

Bone marrow engraftment but limited expansion of hematopoietic cells from multipotent germline stem cells derived from neonatal mouse testis

Multipotent germline stem (mGS) cells derived from neonatal mouse testis, similar to embryonic stem (ES) cells, differentiate into various types of somatic cells in vitro and produce teratomas after inoculation into mice. In the present work, we examined mGS cells for hematopoietic progenitor potential in vitro and in vivo. mGS cells were differentiated on OP9 stromal cells and induced into Flk1(+) cells. Flk1(+) cells were sorted and replated on OP9 stromal cells with various cytokines and emerging hematopoietic cells were analyzed for lineage marker expression by fluorescein-activated cell sorting, progenitor activity by colony assay, and stem cell transplantation assay. mGS cells, like ES cells, produce hematopoietic progenitors, including both primitive and definitive erythromyeloid, megakaryocyte, and B- and T-cell lineages via Flk1(+) progenitors. When transplanted into the bone marrow (BM) of nonobese diabetic/severe combined immunodeficient (NOD/SCID) gammac(null) mice directly, mGS-derived green fluorescent protein (GFP)-positive cells were detected 4 months later in the BM and spleen. GFP(+) donor cells were also identified in the Hoechst33342 side population, a feature of hematopoietic stem cells. However, these mGS-derived hematopoietic cells did not proliferate in vivo, even after exposure to hematopoietic stressors, such as 5-fluorouracil (5FU) injection or serial transplantation. mGS cells produced multipotent hematopoietic progenitor cells with myeloid and lymphoid lineage potential in vitro and localized in the BM after intra-BM injection but, like ES cells, failed to expand or show stem cell repopulating ability in vivo.