FP Group Research Articles

Experimental and Computational Characterization of the Transition State for C–X Bimetallic Oxidative Addition at a Cu–Fe Reaction Center

The heterobimetallic complex (IPr)Cu-Fp (IPr = N,N′-bis(2,6-diisopropylimidazol-2-ylidene, Fp = FeCp(CO)2) was identified previously as a nonprecious metal catalyst for C–H borylation. To better understand the nature of the bimetallic reaction pathways operative in this system, we have conducted a thorough mechanistic study of alkyl halide activation by the Cu–Fe heterobimetallic reaction center. Use of cyclopropylmethyl halide substrates as radical clocks established that alkyl halide activation occurs by a two-electron mechanism for alkyl bromides and chlorides but not iodides. Eyring analysis of the activation of benzyl chloride allowed for experimental determination of activation parameters, including a large and negative entropy of activation (ΔS⧧ = −36 eu). A Hammett study with para-substituted benzyl chlorides revealed a reaction constant of ρ = 1.6, indicating accumulation of negative charge in the transition state on the alkyl halide carbon. The Ru analogue, (IPr)Cu-Rp (Rp = RuCp(CO)2), was found to react approximately 17–25 times more slowly with selected benzyl chlorides than (IPr)Cu-Fp, indicating that the relative nucleophilicities of the free metal carbonyl anions are predictive of the relative reactivities of their heterobimetallic counterparts. Synthesis and characterization of the new Ag and Au analogues, (IPr)Ag-Fp and (IPr)Au-Fp, are reported along with the observation that these more covalent congeners are significantly less reactive toward alkyl halides. DFT calculations were used to model a transition state for the Cu–Fe reaction, which was identified as stereoinvertive at the alkyl halide carbon. NBO calculations indicate crucial roles played by the CO ligands within the Fp group: they both act as redox noninnocent ligands and also provide structural templating to stabilize the transition state as the metal–metal bond breaks.

Effect of selective breeding on collagen properties of Atlantic salmon (Salmo salar L.)

Collagen content and properties of skeletal muscle were studied among selected (FP) and unselected (WP) Atlantic salmon lines that were reared together to avoid any environmental effects. The FP group had significantly higher body weight at harvesting, softer texture and lower connective tissue yield compared with the WP group. The relative collagen fractions (acid, pepsin, insoluble) were similar, but the FP group had a greater abundance of amino acids involved in collagen triple helix conformation and stabilisation (Gly, Pro, Hyp and Hyl), whilst the Lys content was greater for the WP group, indicating a more aggregated collagen. The connective tissue denaturation temperature was lower for the FP group, coinciding with a lower degree of collagen self-assembly and intermolecular-crosslinks. It is concluded that selective breeding has resulted in lower connective tissue stability of Atlantic salmon fillets.

Clinical evaluations of neoadjuvant chemotherapy with DN and FP regimens for patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma

To explore the efficacies and side effects of neoadjuvant chemotherapy with DN (docetaxel plus cisplatin) and FP (nedaplatin plus cisplatin) regimens for patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma. From January 2008 to January 2012, a total of 124 patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma were randomized into DN group (n = 64) and FP group (n = 60). Both groups received neoadjuvant chemotherapy. The treatment schedule was recycled every 3 weeks. After 2 cycles, those with potential surgical resection underwent surgery. The 2-year overall, locoregional relapse-free and distant metastasis-free survival rates in DN and FP groups were 71.1% and 66.7%, 65.0% and 63.0%, 78.3% and 74.3% respectively (P > 0.05). The incidence of leucopenia was higher in DN group than that in FP group (P < 0.05). And the occurrence rates of gastrointestinal toxicity and mucositis were significantly higher in FP group than those in DN group. No perioperative mortality occurred with a low incidence of postoperative complications. The rates of overall response, resection, postoperative complications and pathological complete rates response were similar in two groups. And the rates of downstage and R0 resection were significantly higher in DN group than those in FP group (P < 0.05). For patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma, neoadjuvant chemotherapies of docetaxel and nedaplatin may achieve excellent outcomes in clinical response and 2-year survival rate. And the side effects are clinically acceptable.

Deoxycorticosterone acetate (DOCA) treatment increased blood pressure in female but not male mice under high salt diet

Sex differences in salt sensitivity have been suggested but further study is required. Our purpose was to investigate effects of DOCA-treatment on blood pressure and the renal handling of sodium in mice consuming high salt. DOCA or placebo pellets of 50 mg (Innovative Research of America, Sarasota, FL) were implanted in 4 month-old CD-1 mice (Harlan, Inc., Indianapolis, IN) 3 days before being placed in metabolic cages where they remained for 24 days. Four groups (n=5/group) were used and included female and male placebo (FP, MP) and female and male DOCA, (FDOCA & MDOCA). Mice consumed 4% salt diet and drank 1% saline ad libitum for 24 days. Daily measurements of Na intake (Nai) and Na excretion (Nae) were used to determine Nae/Nai ratio. Mean blood pressure (MBP, mm Hg) was measured daily in all mice via the tail-cuff method. Daily fluid intake and urine flow rates were extensive for DOCA-treated mice (1.0 to 1.5 x body weight). MBP averaged for the 24 day period was higher in the FDOCA group (80.8±1.3) compared to all other groups: FP (72.6±1.2, p<0.001); MDOCA (77.5±0.6, p<0.05); and MP (75.9±1.3, p<0.05). MBP for the FP group was significantly lower than that of other groups and no difference in MBP existed between MDOCA and MP. Nae/Nai data were interesting in that the ratio for the FDOCA group was higher than that for the FP group (81.3±2.8 vs 72.4±3.0, respectively, p<0.05) whereas no difference occurred between the MDOCA and MP groups (82.5±1.8 vs 77.3±2.3, respectively). Results suggest that females may be more salt sensitive than males and lose their sex-dependent protection against hypertension upon high salt consumption. Study supported by Oklahoma INBRE 8P20GM103447 Summer Research Program.

A Double-Blinded Randomized Trial to Compare the Effectiveness of Minimally Invasive Procedures Using Patient-Reported Outcomes

The Institute of Medicine has included the comparison of minimally invasive surgical techniques in its research agenda. This study seeks to evaluate a model for the comparison of minimally invasive procedures using patient-reported outcomes. A double-blinded randomized controlled trial (NCT01489436) was conducted. Baseline data were obtained, standardized anesthesia was induced, and patients were randomized to single-port (SP) or 4-port (FP) laparoscopic cholecystectomy. Perioperative care was standardized. The outcomes were pain (Visual Analog Scale) on postoperative day 1 (primary) and quality of life (Patient-Reported Outcomes Measures Information System and Linear Analog Self-Assessment), serum cytokines, and heart rate variability (secondary). Analysis was intention to treat. Using identical occlusive dressings, patients and the outcomes assessor remained blinded until postoperative day 2. Fifty-five patients were randomized to each arm. There was no difference in demographics. Visual Analog Scale pain score on postoperative day 1 was significantly different from baseline in each group (SP: 1.6 ± 1.9 to 4.2 ± 2.4 vs FP: 1.8 ± 2.3 to 4.2 ± 2.2), but not different from each other (p = 0.83). Patients in the FP arm reported significantly less fatigue on postoperative day 7 than patients in the SP group (3.1 ± 2.1 vs 4.2 ± 2.2; p = 0.009). Fewer patients in the FP group required postoperative oral narcotics before discharge (40% vs 60%; p = 0.056). Cytokines levels and heart rate variability were similar between arms. In patients followed for >1 year, no difference in umbilical hernia rates was noted. Early postoperative quality of life data captured differences in fatigue, indicating improved recovery after FP within a controlled trial. Physiologic measures were similar, suggesting that the differences between SP and FP are minimal.

Cats Infected by Feline Leukemia Virus—Morpho-Quantitative Evaluation of the Thymus

The feline leukemia virus (FeLV) is a complex disease that affects mainly the immune and hematological systems of cats. And because the thymus was closely associated with the immune system, the aim of this study was to quantify the morphological changes in the thymus of naturally infected and uninfected animals. Thymus morphological changes were evaluated by quantifying the following parameters: thymocytes, fat tissue, thymic corpuscles, connective tissue, and type I and III collagen. This study analyzed a total of seven cats, five in the negative group (Fn) and two in the positive (Fp) group. The areas occupied by thymocytes in FeLV negative (Fn) and positive (Fp) animals were, respectively, 55.16% ± 6.15% and 44.81% ± 6.15% (p = 0.39); adipocytes, 42.14% ± 5.97% (Fn) and 53.42% ± 11.3% (Fp) (p = 0.34); blood vessels, 0.85% ± 0.24% (Fn) and 1.75% ± 0.52% (Fp) (p = 0.15). Whereas thymic corpuscles occupied an area of 0.68% ± 0.19% in negative animals (Fn) only. The connective tissue covered area varied between 12.05% ± 0.68% (Fn) and 10.34% ± 0.62% (Fp) (p = 0.009). Collagen type I (p = 0.30) and type III (p = 0.59) were present in, respectively, 1.73% ± 0.3% and 0.44% ± 0.09% in Fn, and 1.44% ± 0.36 and 0.44% ± 0.13% in Fp. The FeLV virus was not able to completely modify the thymus structure of infected animals, considering the areas occupied by thymocytes, adipose tissue, blood vessels and also type I and III collagens. However, the connective tissue underwent a certain degree of remodeling since less connective tissue area was observed in FeLV infected animals. The absence of thymic corpuscles in immunosuppressed animals suggests a possible connection to thymopoiesis.

Transplantation of mouse ovarian tissue: Comparison of the transplantation sites

Many studies have shown that ischemic injuries during the transplantation process were more detrimental than cryoinjuries for follicle survival and death, and it has been reported that transplantation sites can affect the outcomes of grafted ovarian tissue (OT). The purpose of this study was to assess the impact of different OT transplantation sites on follicular integrity and function of OT grafts. B6D2F1 mice were randomly assigned to control (sham) and four experimental groups according to transplantation sites (back muscle [BM], fat pad [FP], kidney capsule [KC], and subcutaneous [SC]). The ovaries from four groups were autotransplanted to each site. The OT recovery ratios on Days 2, 7, and 21 were significantly decreased in the FP group. The mean numbers of follicles were significantly lower in all the grafting groups compared with the sham group, except in the KC group on Days 7 and 21 and the BM group on Day 21. On Day 2, all the experimental groups showed low intact (G1) follicle ratio when compared with the sham group; however, the BM, KC, and FP groups recovered their morphologic integrity on Day 7, and only the SC group presented a significant decrease in G1 follicle ratios. On Day 21, the G1 follicle ratios of the FP and KC groups were greater than the sham control group. The proportion of apoptotic follicles of the four OT graft groups was higher than in the sham group on Day 2, followed by a significant decrease in the KC group and an increase in the SC group on Day 7. The serum follicle-stimulating hormone levels were significantly increased in all grafting groups on Day 2. On Day 7, only the SC group showed the high follicle-stimulating hormone level compared with the other groups. The mean numbers of oocytes from OT grafts were the highest in the KC group, except in the control group, and the lowest in the SC group. The ratios of mature oocytes were also significantly greater in the sham and KC groups. However, the ratios of normal spindle did not differ among the five groups. In conclusion, the KC was the optimal site for OT transplantation in this murine model, whereas the SC site was unfavorable for this procedure. In this study, we confirmed that the different grafting sites influenced the outcomes of transplantation.

The Efficacy of Incorporating Partial Squats in Maximal Strength Training

The purpose of our study was to examine the effects of 2 different training methods on dynamic and isometric measures of maximal strength. Seventeen recreationally trained men (1 repetition maximum [1RM] squat: 146.9 ± 22.4 kg) were assigned to 2 groups: full range of motion (ROM) squat (F) and full ROM with partial ROM squat (FP) for the 7-week training intervention. Repeated measures analysis of variance revealed that there was a statistically significant group-by-time interaction for impulse scaled at 50, 90, and 250 milliseconds at 90° of knee flexion and rate of force development at 200 milliseconds with 120° of knee flexion (p ≤ 0.05). There was also a statistically significant time effect (p ≤ 0.05) for the 1RM squat, 1RM partial squat, isometric squat peak force allometrically scaled (IPFa) 90°, IPFa 120°, and impulse allometrically scaled at 50, 90, 200, and 250 milliseconds at 90° and 120° of knee flexion. Additionally, the FP group achieved statistically larger relative training intensities (%1RM) during the final 3 weeks of training (p ≤ 0.05). There was a trend for FP to improve over F in 1RM squat (+3.1%, d = 0.53 vs. 0.32), 1RM partial squat (+4.7%, d = 0.95 vs. 0.69), IPFa 120° (+5.7%, d = 0.52 vs. 0.12), and impulse scaled at 50, 90, 200, and 250 milliseconds at 90° (+6.3 to 13.2%, d = 0.50-1.01 vs. 0.30-0.57) and 120° (+3.4 to 16.8%, d = 0.45-1.11 vs. 0.08-0.37). These larger effect sizes in the FP group can likely be explained their ability to train at larger relative training intensities during the final 3 weeks of training resulting in superior training adaptations. Our findings suggest that partial ROM squats in conjunction with full ROM squats may be an effective training method for improving maximal strength and early force-time curve characteristics in men with previous strength training experience. Practically, partial squats may be beneficial for strength and power athletes during a strength-speed mesocycle while peaking for competition.

Effects of different sequences of intravenous administration on fentanyl-induced cough during induction of general anesthesia

Objective To evaluate the effects of different sequences of intravenous administration on fentanyl-induced cough during induction of general anesthesia.Methods One hundred patients of both sexes,aged 18-70 yr,weighing 42-88 kg,of ASA physical status Ⅰ or Ⅱ,scheduled for elective surgery under general anesthesia,were equally randomized to 2 groups using a random number table:fentanyl-propofol group (group FP) and propofol-fentanyl group (group PF).In FP group,fentanyl 3 μg/kg was injected intravenously over 3 s,and then propofol 1.5 mg/kg was injected intravenously.In PF group,propofol 1.5 mg/kg was injected intravenously,and then fentanyl 3μg/kg was injected intravenously over 3 s.The development,intensity and onset time of cough were recorded within 1 min after fentanyl injection.Results Compared with FP group,the incidence of cough was significantly decreased,and no significant change was found in the intensity and onset time of cough in PF group.Conclusion Administration in the propofol-fentanyl sequence can reduce the development of fentanyl-induced cough as compared with that in the fentanyl-propofol sequence during induction of general anesthesia. Key words: Fentanyl; Propofol ; Cough ; Anesthesia, general

Effects of vaginal delivery, cesarean section and exposure to labor on endothelial function of pregnant women

IntroductionThis study was undertaken to assess the influence of labor and cesarean section on endothelial function. Materials and MethodsFlow-mediated vasodilatation (FMD) was measured before and after delivery for an assessment of endothelial function in three groups: (1) the Vaginal delivery group (with spontaneous labor or induction of labor, n=48), (2) the Elective C/S group (with a cesarean planned, n=20), and (3) the C/S after FP group (scheduled for vaginal delivery but required to have an emergency cesarean section because of failure in progress, n=11). ResultsThere were statistically significant changes between the antepartum and postpartum FMD values in the Vaginal delivery group and the Elective C/S group but not in the C/S after FP group (P<0.001, P=0.023 and P=0.22 respectively). ConclusionsThese observations suggest that labor may enhance endothelial function and that cesarean section may impair endothelial function.

Periprosthetic supracondylar femoral fractures following total knee arthroplasty: clinical comparison and related complications of the femur plate system and retrograde-inserted supracondylar nail

BackgroundThe purpose of this study is to analyze the clinical results and related complications of the femur plate system (FP) and the retrograde-inserted supracondylar nail (RISN).Materials and methodsThe study included 42 cases of periprosthetic supracondylar femoral fractures (PSF) proximal to posterior stabilized total knee arthroplasty between 2005 and 2009. Twenty-four cases of PSF were treated with the FP, and the other 18 cases were treated with the RISN. This study cohort was divided into subgroups according to the AO classification. We retrospectively compared the clinical results between the FP and RISN group.ResultsThere were no significant differences between the two groups in terms of time of clinical union (p = 0.649). In the subgroup analysis, the mean operation time was significantly different only in subgroup A1 (p = 0.03). Complications were seen in 29.2 % (7/24) of patients in the FP group and 27.8 % (5/18) in the RISN group. The age during the index TKA and fracture fixation was a significant risk (p = 0.008) factor for complications between the two groups. No significant differences were found in the other factors between the two groups. The p value for operative time (p = 0.223), immobilization period (p = 0.129), ROM (p = 0.573), KSS (p = 0.379), KSS functional scores (p = 0.310) and time to union (p = 0.649).ConclusionClinical results did not differ according to the treatment methods used. Fixation method and fracture type did not cause an increase in the complication rate, but there was a trend toward higher non-union rates with the FP method and higher re-fracture rate with the RISN method. Noting the fact that only increasing age correlated with an increased complication rate, more careful attention should be paid to elderly patients in terms of both prevention and surgical care.Level of evidenceLevel III, therapeutic study.

Development of a novel marking system for laparoscopic gastrectomy using endoclips with radio frequency identification tags: feasibility study in a canine model

Intraoperative identification of early gastric cancer is difficult to conduct during laparoscopic procedures. In this study, we investigated the feasibility and accuracy of a newly developed marking system using endoclips with radio frequency identification (RFID) tags in a canine model. RFID is a wireless near field communication technology. Among the open frequency bands available for medical use, 13.56 MHz is suitable for a surgical marking system because of the similar and linear signal decay both in air and in biological tissues. The proposed system consists of four parts: (a) endoclips with RFID tags, (b) endo-clip applier equipment, (c) laparoscopic locating probe, and (d) signal processing units with audio interface. In the experimental setting using canine models, RFID-tagged endoclips were applied to the mucosa of each dog's stomach. During the subsequent operation, the clips with RFID tags placed in five dogs were located by the detection of the RFID signal from the tag (RFID group), and the conventional clips in the other six dogs were located by finger palpation (FP group). The detected sites were marked by ablation on the serosal surface. Distance between the clips and the metal pin needles indicating ablated sites were measured with X-ray radiographs of the resected specimen. All clips were successfully detected by the marking system in the RFID group (10/10) and by finger palpation in the FP group (17/17). The medians of detection times were 31.5 and 25.0 s, respectively; the distances were 5.63 and 7.62 mm, respectively. The differences were not statistically significant. No adverse event related to the procedures was observed. Endoclips with RFID tags were located by our novel marking system in an experimental laparoscopic setting using canine stomachs with substantial accuracy comparable to conventional endoclips located by finger palpation through an open approach.

Effects of fructose-1, 6-diphosphate pretreatment on lung injury induced by hepatic cold ischemia-reperfusion in rats

Objective To evaluate the effects of fructose-1 ,6-diphosphate （FDP） pretreatment on lung injury induced by hepatic cold liver ischemia-reperfusion in rats .Methods Eighteen healthy male Sprague-Dawley rats were randomly divided into 3 groups （n= 6 each） using a random number table ：sham operation group （S group） ,hepatic cold liver ischemia-reperfusion model group （M group） ,and FDP pretreatment group （FP group） . The animals were anesthetized with intraperitoneal chloral hydrate and kept spontaneous breathing .Laparotomy was performed ,and the related blood vessels were only isolated in group S .Hepatic cold ischemia-reperfusion was induced in M and FP groups .In FP group ,FDP 250 mg/kg was injected via the caudal vein at 15 min before skin incision .At 6 h of reperfusion ,the bronchoalveolar lavage fluid （BALF） was collected to detect the levels of tumor necrosis factor-α（TNF-α） ,interleukin-10 （IL-10） and nitric oxide （NO） by ELISA .Lungs were removed for microscopic examination of the pathological changes by light microscopy .Real-time PCR was used to detect the expression of iNOS mRNA .Results Compared with S group , the levels of TNF-α and NO in BALF were significantly increased , the expression of iNOS mRNA was up-regulated , and the level of IL-10 in BALF was decreased in M and FP groups （ P〈0.05 ） .Compared with M group ,the levels of TNF-αand NO in BALF were significantly decreased ,the expression of iNOS mRNA was down-regulated ,and the level of IL-10 in BALF was＆nbsp;increased in FP group （ P〈0.05 ） .The pathological changes of lungs were significantly attenuated in FP group as compared with M group .Conclusion FDP pretreatment can obviously attenuate lung injury induced by hepatic cold ischemia-reperfusion in rats ,and inhibition of iNOS expression ,reduction of NO synthesis ,and decrease in inflammatory responses are involved in the mechanism . Key words: Fructose; Liver; Lung; Reperfusion injury

Synthesis, Cyclization, and Migration Insertion Oligomerization of CpFe(CO)2(CH2)3PPh2 in Solution

Cyclopentadienyldicarbonyl[(diphenylphosphino)propyl]iron (CpFe(CO)2(CH2)3PPh2, FpP), containing both Fp and phosphine groups, was synthesized as a difunctional monomer for migration insertion polymerization (MIP). FpP underwent either intra- or intermolecular reactions in solution. When a solution with low FpP concentration (ca.1% by weight) was left at 25 °C, FpP was quantitatively converted to the five-membered-ring species 1 via CO release. On the other hand, when a solution at the same low concentration was heated to 70 °C in the dark, an intramolecular migration insertion reaction was promoted, leading to a high conversion of FpP (ca. 70%) to the six-membered cyclic Fp acyl derivatives 2. At the same temperature with an increase in the concentration of FpP to 10% by weight, intermolecular MIR became predominant (ca. 90%) with a low yield of ring molecules (ca. 10%). Solution polymerization of FpP (ca. 20% by weight) was therefore performed at 70 °C, which generated both THF-soluble and -insoluble ma...

Dupuytren contracture: comparative study between partial fasciectomy and percutaneous fasciectomy

ObjectivesTo compare the clinical results obtained by using the techniques of open limited fasciectomy (FP) and percutaneous needle fasciectomy (FPC) in patients with Dupuytren's contracture after one year follow up. MethodsThirty-three patients and a total of 50 fingers with Dupuytren's contracture were divided non-randomly and evaluated after undergoing procedures with FP or FPC. The results were evaluated based on the Tubiana classification, DASH score (Disabilities of the Arm, Shoulder, and Hand), time until return to professional activities, total passive extension deficit (DTEP), the relationship between the extension deficit and DASH, recurrence and complications. ResultsTwenty-six fingers were treated with FPC technique and 24 fingers with FP. The DTEP was significantly lower in FP group (10.23°) when compared to FPC group (23.46°) at 12 months postoperatively (p=0.038). The remaining items assessed did not show any statistically significant differences. ConclusionTotal passive extension deficit at 12 months is lower in the group of open limited fasciectomy. There are no significant differences between groups FP and FPC over the classification of Tubiana, the DASH score, time until return to professional activities and the incidence of recurrence.

Contratura de Dupuytren: estudo comparativo entre fasciectomia parcial e fasciotomia percutânea

ObjectivesTo compare the clinical results obtained by using the techniques of open limited fasciectomy (FP) and percutaneous needle fasciotomy (FPC) in patients with Dupuytren's contracture after one year follow up. MethodsThirty-three patients and a total of 50 fingers with Dupuytren's contracture were divided non-randomly and evaluated after undergoing procedures with FP or FPC. The results were evaluated based on the Tubiana classification, DASH score (Disabilities of the Arm, Shoulder, and Hand), time until return to professional activities, total passive extension deficit (DTEP), the relationship between the extension deficit and DASH, recurrence and complications. ResultsTwenty-six fingers were treated with FPC technique and 24 fingers with FP. The DTEP was significantly lower in FP group (10,23°) when compared to FPC group (23,46°) at 12 months postoperatively (p=0,038). The remaining items assessed did not show any statistically significant differences. ConclusionTotal passive extension deficit at 12 months is lower in the group of open limited fasciectomy. There are no significant differences between groups FP and FPC over the classification of Tubiana, the DASH score, time until return to professional activities and the incidence of recurrence.

Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis

Esophageal squamous cell cancer (ESCC) is a high-grade carcinoma that is treated with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by surgery. Despite some success with these therapies, overall survival remains poor. In order to investigate a newer CRT regimen, we designed a comparative study to evaluate preoperative CRT using docetaxel (DOC) or 5-Fluorouracil and cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a retrospective review of patients with resectable, locally advanced ESCC, 95 patients received preoperative CRT between 2001 and 2007. CRT was administered using either FP (n = 40) or DOC (n = 55). Pathological response and clinical outcomes were compared between the two groups. Hazard ratios and time-to-event analyses were used to assess outcomes; the ratios were controlled by multivariate logistic regression analysis of potential prognostic factors, and survival was presented with Kaplan-Meier curves. In the FP group, a significant curative effect was observed on the basis of pathological examination of postoperative lesions. However, the DOC group presented a significantly better prognosis on the basis of cumulative survival rates. Logistic regression analysis revealed that the presence of five or more lymph node metastases was an independent predictor of reduced survival. Patients with lymph node metastasis exhibited a better prognosis in the DOC group than those in the FP group. Preoperative CRT for locally advanced esophageal cancer using DOC results in similar or better long-term outcomes compared with FP-based CRT. Therefore, CRT using DOC is a promising therapy option for esophageal cancer.

Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport

To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

1913 WEAK EXPRESSION OF FAS LIGAND IN NEPHRECTOMIZED TUMORS PREDICTS LONG-TERM PROGRESSION-FREE SURVIVAL DURING TREATMENT BY INTERFERON Α IN METASTATIC RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Advanced (II)1 Apr 20131913 WEAK EXPRESSION OF FAS LIGAND IN NEPHRECTOMIZED TUMORS PREDICTS LONG-TERM PROGRESSION-FREE SURVIVAL DURING TREATMENT BY INTERFERON Α IN METASTATIC RENAL CELL CARCINOMA Takehiro Sejima, Hideto Iwamoto, Toshihiko Masago, Shuichi Morizane, Akihisa Yao, Tadahiro Isoyama, and Atsushi Takenaka Takehiro SejimaTakehiro Sejima Yonago, Japan More articles by this author , Hideto IwamotoHideto Iwamoto Yonago, Japan More articles by this author , Toshihiko MasagoToshihiko Masago Yonago, Japan More articles by this author , Shuichi MorizaneShuichi Morizane Yonago, Japan More articles by this author , Akihisa YaoAkihisa Yao Yonago, Japan More articles by this author , Tadahiro IsoyamaTadahiro Isoyama Yonago, Japan More articles by this author , and Atsushi TakenakaAtsushi Takenaka Yonago, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2332AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To determine the role of the immune system in patients with metastatic renal cell carcinoma (RCC), we investigated the relationship between metastatic characteristics, immunological parameters including expression of Fas ligand (FasL) in nephrectomized tumors and patient prognosis. METHODS 1) Stratification into three groups; forty-five patients with metastatic RCC had undergone nephrectomy followed by Interferon (IFN) α treatment were stratified into three groups based on the time of metastasis occurrence (i.e., at first presentation [METS at FP, n = 14], within five years of nephrectomy [early recurrence, n = 17] and five years after nephrectomy [late recurrence, n = 14]). Patient prognosis (i.e., progression-free survival [PFS] during IFN α treatment and overall survival [OS] from metastasis occurrence) and immunological parameters (i.e., neutrophil / lymphocyte ratio [NLR], serum albumin and FasL expression in RCC) were compared among the groups. FasL expression was analyzed by immunohistochemistry (IHC) and mRNA quantification. 2) Stratification into two groups; forty-five patients were stratified into two groups based on FasL positivity as determined by IHC. Patient prognosis and the aforementioned immunological parameters were compared between the groups. RESULTS 1) The patients in the late recurrence group had significantly longer PFS during IFN α treatment and OS compared to those in the other two groups. The NLR was significantly lower in the late recurrence group than in the METS at FP (P < 0.0001) and early recurrence (P = 0.0043) groups. The FasL mRNA expression was significantly lower in the late recurrence group than in the METS at FP (P = 0.0016) and early recurrence (P = 0.0076) groups. 2) The PFS during IFN α treatment was significantly longer in the FasL-negative (n = 18; median 18.4 mo.) than in the FasL-positive (n = 27; median 11.6 mo.) group (P = 0.0475). The NLR was significantly lower in the FasL-negative than in the FasL-positive group (P = 0.0085). CONCLUSIONS Our results suggest that strong host immune activity as determined by the effectiveness of IFN α treatment and OS in metastatic RCC is associated with delayed occurrence of metastasis, high peripheral blood lymphocyte activity and low FasL expression in nephrectomized tumors. “FasL counter attack” may occur in metastatic RCC; that is, FasL on the surface of circulating tumor cells binds to the Fas receptor on peripheral blood lymphocytes and diminishes the effectiveness of IFN α treatment. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e784-e785 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takehiro Sejima Yonago, Japan More articles by this author Hideto Iwamoto Yonago, Japan More articles by this author Toshihiko Masago Yonago, Japan More articles by this author Shuichi Morizane Yonago, Japan More articles by this author Akihisa Yao Yonago, Japan More articles by this author Tadahiro Isoyama Yonago, Japan More articles by this author Atsushi Takenaka Yonago, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

38 GENERATION OF INTERSPECIFIC CLONED BLASTOCYSTS BY ZONA PELLUCIDA-FREE NUCLEAR TRANSFER IN WILD FELIDS

Somatic cell nuclear transfer is an assisted reproductive technique that could help to preserve endangered species. Because it is difficult to obtain wild felid oocytes, interspecific cloning using domestic cat (DC) oocytes is an alternative to produce cloned embryos in these species. The aim of this study was to evaluate different cloning strategies in the DC (Felis silvestris catus) and to use the most efficient strategy to generate wild felid embryos by interspecific cloning. First, we evaluated 3 different cloning strategies: (1) enucleation of DC oocytes with zona pellucida (ZP) followed by fusion of a DC fibroblast that was injected into the perivitelline space (ZP-enclosed group), (2) the same enucleation procedure followed by intracytoplasmic injection of a DC fibroblast (ZPi group), and (3) enucleation of ZP-free oocytes followed by adhesion and fusion of a DC fibroblast (ZP-free group). After 2 h of nuclear reprogramming, the reconstructed embryos were activated with 5 µM ionomycin and 1.9 mM DMAP, and cultured in SOF. The ZP-free embryos were cultured in wells of the well system. Embryo development among treatment groups was compared by the Fisher exact test (P ≤ 0.05). The blastocyst rates were similar among the 3 groups: 11.1% (2/18), 11.1% (5/45), and 12.7% (9/71), for ZP-enclosed, ZPi, and ZP-free, respectively. However, the quantity of reconstructed embryos after the procedure was higher in the ZP-free clones because of a higher fusion rate (82.7 vs. 25.4%) and the use of a less-invasive technique than the injection. Moreover, the percentage of expanded blastocysts was also higher (0, 16.2, and 77.8% for ZP-enclosed, ZPi, and ZP-free, respectively). Parthenogenetic controls, with and without ZP, did not differ in blastocyst rates: 47.7% (42/88) and 49.4% (38/77), respectively. After this, the ZP-free strategy was chosen for the successive experiment. In experiment 2, the wild felid species selected for interspecific cloning were Bengal (a hybrid between Felis silvestris and Prionailurus bengalensis; FP group), cheetah (Acinonyx jubatus; AJ group), and tiger (Panthera tigris; PT group). The morula and blastocyst rates were higher in the FP group: 34.3% (36/105), 16.2% (16/99), and 17.5% (11/63) for morulae, and 33.3% (35/105), 1% (1/99), and 3.2% (2/63) for blastocysts of FP, AJ, and PT, respectively. Additionally, total cell number and the expression pattern of octamer-binding transcription factor 4 (Oct-4) were examined in the blastocysts by immunocytochemistry. The mean total cell number in DC, FP, AJ, and PT blastocysts was 177.9 ± 53, 229 ± 40, 53, and 41, respectively. All blastocysts expressed Oct-4 but in different proportions. The percentage of cells expressing Oct-4 in DC, FP, AJ, and PT blastocysts was 48, 66, 100, and 98%, respectively. In summary, ZP-free cloning was found to be an efficient technique in DC, with potential to be used in wild felid species. We also demonstrated that DC oocytes were able to reprogram cells of other genera. This is the first report of felid ZP-free cloning and also the first time that tiger and cheetah embryos were produced by interspecific cloning.