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The cyclooxygenase-2 (COX-2) enzyme is part of the inflammatory pathway and is induced within the brain by a variety of pathological events, including ischemia. Pharmacological agents that inhibit COX-2 have been found to be neuroprotective in a number of injury models, and long-term administration of these drugs has been shown to induce plastic changes in the brain. In the current experiment, we investigated the effectiveness of stimulating cortical plasticity following stroke injury through the administration of the COX-2 inhibitor drug NS398. Furthermore, we determined whether the induced plastic changes improved functional outcome following motor cortex stroke. Chronic drug administration was found to induce dendritic hypertrophy in cells in the parietal cortex, and this anatomical change was associated with the animals making significantly more reach attempts, as well as successful reaches during a skilled reaching task. Additional motor tests however revealed that the treatment did not affect the level of motor recovery, as the animals showed chronic impairments in the Schallert cylinder, and the forepaw inhibition tasks. Short-term administration of the drug, immediately following the stroke did not induce any dendritic changes, nor was it found to improve behavioral performance on any of the motor tasks. Based on these results we conclude that the plastic changes that are induced by long-term COX-2 inhibitor administration provide some benefit to functional outcome following ischemic cortical injury. 相似文献
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Rhoda Raji Federica Guzzo Luisa Carrara Joyce Varughese Emiliano Cocco Stefania Bellone Marta Betti Paola Todeschini Sara Gasparrini Elena Ratner Dan-Arin Silasi Masoud Azodi Peter Schwartz Thomas J Rutherford Natalia Buza Sergio Pecorelli Alessandro D Santin 《Journal of experimental & clinical cancer research : CR》2011,30(1):106
Background
We evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines.Materials and methods
Trop-2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium-release assays against UMMT and OMMT cells.Results
Trop-2 expression was elevated in 9 of 26 (35%) UMMT and 8 of 14 (57%) OMMT tissues tested by IHC. Positivity for Trop-2 mRNA by RT-PCR and surface expression by flow cytometry were detected in 2 of 4 cell lines, with high positivity noted in OMMT-ARK-2. OMMT-ARK-2 was highly sensitive to hRS7 ADCC (range: 34.7-41.0%; P < 0.001) with negligible cytotoxicity seen in the absence of hRS7 or in the presence of control antibody (range: 1.1-2.5%). Human IgG did not significantly inhibit ADCC while human complement increased, hRS7-mediated-cytotoxicity against OMMT-ARK-2.Conclusion
Trop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2. 相似文献3.
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Clostridium perfringens enterotoxin C‐terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy‐resistant ovarian cancer
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Emiliano Cocco Erik M. Shapiro Sara Gasparrini Salvatore Lopez Carlton L. Schwab Stefania Bellone Ileana Bortolomai Natalia J. Sumi Elena Bonazzoli Roberta Nicoletti Yang Deng W. Mark Saltzman Caroline J. Zeiss Floriana Centritto Jonathan D. Black Dan‐Arin Silasi Elena Ratner Masoud Azodi Thomas J. Rutherford Peter E. Schwartz Sergio Pecorelli Alessandro D. Santin 《International journal of cancer. Journal international du cancer》2015,137(11):2618-2629
Identification of micrometastatic disease at the time of surgery remains extremely challenging in ovarian cancer patients. We used fluorescence microscopy, an in vivo imaging system and a fluorescence stereo microscope to evaluate fluorescence distribution in Claudin‐3‐ and ‐4‐overexpressing ovarian tumors, floating tumor clumps isolated from ascites and healthy organs. To do so, mice harboring chemotherapy‐naïve and chemotherapy‐resistant human ovarian cancer xenografts or patient‐derived xenografts (PDXs) were treated with the carboxyl‐terminal binding domain of the Clostridium perfringens enterotoxin (c‐CPE) conjugated to FITC (FITC‐c‐CPE) or the near‐infrared (NIR) fluorescent tag IRDye CW800 (CW800‐c‐CPE) either intraperitoneally (IP) or intravenously (IV). We found tumor fluorescence to plateau at 30 min after IP injection of both the FITC‐c‐CPE and the CW800‐c‐CPE peptides and to be significantly higher than in healthy organs (p < 0.01). After IV injection of CW800‐c‐CPE, tumor fluorescence plateaued at 6 hr while the most favorable tumor‐to‐background fluorescence ratio (TBR) was found at 48 hr in both mouse models. Importantly, fluorescent c‐CPE was highly sensitive for the in vivo visualization of peritoneal micrometastatic tumor implants and the identification of ovarian tumor spheroids floating in malignant ascites that were otherwise not detectable by conventional visual observation. The use of the fluorescent c‐CPE peptide may represent a novel and effective optical approach at the time of primary debulking surgery for the real‐time detection of micrometastatic ovarian disease overexpressing the Claudin‐3 and ‐4 receptors or the identification of residual disease at the time of interval debulking surgery after neoadjuvant chemotherapy treatment. 相似文献
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Solomon D Shariff AH Silasi DA Duffy AJ Bell RL Roberts KE 《Surgical endoscopy》2012,26(10):2823-2827
Objective
This report describes the first prospective cohort study comparing transvaginal cholecystectomies (TVC) with single incision laparoscopic cholecystectomies (SILC) and four-port laparoscopic cholecystectomies (4PLC).Methods
Between May 2009 and August 2010, 14 patients underwent a TVC. These patients were compared with patients who underwent SILC (22 patients) or 4PLC (11 patients) in a concurrent, randomized, controlled trial. Demographic data, operative time, numerical pain scales, complications, and return to work were recorded.Results
Mean age (TVC: 33.5?±?3.0?year; SILC: 38.4?±?3.3?year; 4PLC: 35.5?±?4.1?year; p?=?0.58) and mean BMI (TVC: 28.8?±?1.5?kg/m2; SILC: 31.8?±?1?kg/m2; 4PLC: 31.4?±?2.2?kg/m2; p?=?0.35) were not statistically significant. However, mean operative time (TVC: 67?±?3.9?min; SILC: 48.9?±?2.6?min; 4PLC: 42.3?±?3.9?min; p?0.001) was significantly longer for TVC. Numerical pain scales showed significantly lower pain scores on POD 1 and 3 for TVC compared with SILC and 4PLC (TVC: 4.1?±?0.5 and 2.9?±?0.7; SILC: 6.1?±?0.5 and 5.3?±?0.5; 4PLC: 5.7?±?0.4 and 4.7?±?0.3; p?=?0.02) with equilibration of pain scores by days 14 and 30. Return to work (TVC: 6.4?±?1.5?days; SILC: 13.1?±?1.3?days; 4PLC: 14.1?±?1.4?days; p?0.001) also was significantly faster for patients in the TVC group. One conversion in the TVC group to a 4PLC was necessary due to adhesions within the pelvis. One dislodged IUD was seen and immediately replaced in the TVC group. One hernia was observed in the SILC group.Conclusions
Transvaginal cholecystectomy is a safe and well-tolerated procedure with statistically significantly less pain at 1 and 3?days after surgery, with a faster return to work but longer operative times compared with single incision and four-port laparoscopic cholecystectomy. 相似文献7.
Michelle Silasi Gil Mor 《American journal of reproductive immunology (New York, N.Y. : 1989)》2012,68(4):279-281
A recent study in the journal Science offers insights into the mechanism behind feto‐maternal tolerance, as evidenced by changes in the immuno‐logical environment of the uterus and decidua. They also provide a rich area of research for the understanding of the regulation of the immune system in other complicated medical conditions, including cancer and pregnancies affected by infection or autoimmunity. 相似文献
8.
Gergely Silasi Jennifer She Jamie D Boyd Songchao Xue Timothy H Murphy 《Journal of cerebral blood flow and metabolism》2015,35(5):734-738
We developed a mouse model of small-vessel disease where occlusions are produced through endovascular injection of fluorescent microspheres that target ~12 μm diameter penetrating arterioles and can be localized in histology. Using Thy1-GFP transgenic mice, we visualized the impact of microocclusions on neuronal structure. Microocclusions in the hippocampus produce cell loss or neuronal atrophy (~7% of lodged microspheres led to microinfarcts), while axons within white matter tracts, as well as the striatum and thalamus became blebbed or disrupted. Although the neocortex contained more occlusions than other structures, labeled layer 5 neurons were relatively resistant to structural damage, with <2% of the lodged microspheres producing obvious neuronal damage. 相似文献
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Hyperthermia accelerates and increases ischemic brain damage. Owing to overlapping mechanisms of injury, many assume that hyperthermia also worsens outcome after intracerebral hemorrhage (ICH). However, clinical data do not conclusively prove this, and there is only one animal study examining the impact of hyperthermia. In that study (MacLellan and Colbourne, 2005), several hyperthermia protocols were administered after collagenase-induced ICH in rats; none worsened injury. While the collagenase model is widely used, it differs in important ways from another common model - injecting autologous blood directly into the brain. Thus, we evaluated the impact of immediate hyperthermia (HYP, 39 °C for 3 hr) after a 100-μL infusion of blood into the striatum of rats. This treatment, which markedly increases ischemic damage, was compared to control rats kept normothermic (NOR, 37 °C). Three separate experiments were done to measure: 1) edema at 24 hr, 2) edema at 72 hr, and 3) behavioral impairment and lesion size out to 1 month post-ICH. The HYP treatment did not significantly affect edema at 24 hr, but surprisingly, it modestly reduced edema at 72 hr and partly improved behavioral outcome. However, there were no lasting effects of HYP on behavior (e.g., skilled reaching) or the volume of tissue lost (NOR: 14.0 mm(3) vs. HYP: 14.5 mm(3)). In summary, our findings do not support the common belief that hyperthermia worsens outcome after ICH. Additional research is needed to determine whether more severe or prolonged heating or fever and its cause (e.g., infection) affect morbidity and mortality after ICH. 相似文献