The Importance of Exposure Time in Regional Chemotherapy: Mitomycin C and Fluoropyrimidines1

Author(s):  
E. A. de Bruijn ◽  
P. H. Th. J. Slee ◽  
P. J. K. Kuppen ◽  
R. M. van der Hoeven ◽  
U. R. Tjaden ◽  
...  
2006 ◽  
Vol 18 (2) ◽  
pp. 206 ◽  
Author(s):  
M. C. Gómez ◽  
J. A. Jenkins ◽  
M. López ◽  
M. A. Serrano ◽  
C. Dumas ◽  
...  

Nondomestic cat cloned embryos created by intergeneric nuclear transfer (ig-NT) have lower rate of blastocyst development than that observed in cloned embryos produced by inter-species NT. One promising technique for increasing the efficiency of ig-NT is to use embryonic stem cells (ESC) derived from the pluripotent inner cell mass (ICM) of pre-implantation blastocysts. Mouse embryonic fibroblasts (MEF) are commonly used as feeder cells to support the growth of human and mouse ESC, but they do not always maintain human ESC in an undifferentiated state and carry the risk of transmitting mouse retroviral virus and other pathogens. Thus, it is important to determine whether domestic cat embryonic fibroblasts (DCEF) are able to support cat ESC growth. Proliferation of MEF cells is inhibited before their use as feeder layers by exposure to gamma irradiation or Mitomycin-C. Therefore, in the present study, we determined what concentration of Mitomycin-C was required to inhibit proliferation of DCEF and MEF cells without affecting viability. Embryonic fibroblasts were generated from fetuses collected from a single pregnant domestic cat and mouse at 30 and 14 days of gestation, respectively. Tissue was minced and cultured in DMEM for 7 to 10 days before freezing and storage at −196°C. After thawed DCEF and MEF cells reached 80 to 100% confluence, proliferation was inhibited by exposure to 10, 30, or 40 µg of Mitomycin-C for 2.5 or 5 h. Cells were then washed and labeled with BrdU to measure DNA synthesis as a specific marker for replication. For cytotoxicity, cells were labeled with a dual fluorescent stain to evaluate membrane integrity and esterase activity. The amounts of DNA-labeled BrdU as well as calcein and ethidium homodimer-1 incorporated into the cells were quantified by flow cytometry (see Table 1). Proliferation of DCEF and MEF cells was affected similarly by both concentration and exposure time to Mitomycin-C, with the highest inhibition of DCEF cells occurring after treatment with 40 μg for 5 h (92% not replicating). Cell viability was influenced by both concentration and exposure time to Mitomycin-C, with the highest survival of DCEF cells occurring after exposure to 30 μg for 5 h (90%) and in MEF cells after exposure to 40 μg for 2.5 h (88% viable). In summary, these results indicate that cell proliferation of DCEF can be inhibited by Mitomycin-C, but a higher dosage and longer exposure time should be considered for use compared to the dosage commonly employed for inhibiting cell proliferation of MEF. High concentrations of Mitomycin-C did not significantly increase cytotoxicity of cells in either species. Table 1.


2002 ◽  
Vol 17 (2) ◽  
pp. 227-229
Author(s):  
Osamu Watanabe ◽  
Shunsuke Haga ◽  
Hiroyuki Kato ◽  
Toshinori Ooishi ◽  
Satoshi Kobayashi ◽  
...  

Ophthalmology ◽  
1995 ◽  
Vol 102 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Gordana Sunaric Mégevand ◽  
John F. Salmon ◽  
Raoul P. Scholtz ◽  
Anthony D.N. Murray

2016 ◽  
Vol 12 (1) ◽  
Author(s):  
Nadeem Hafeez Butt ◽  
Abdul Hye ◽  
Muhammad Hammad Ayub ◽  
Saleem Akhtar ◽  
Samina Jahangir

Topical application of mitomycin C has significantly increased the success rate of trabeculectomy. However the optimum exposure time of mitomycin C to the filtration site is not known. . The purpose of this study was to determine whether adequate post-operative control of IOP and a lower incidence of post operative complications can be achieved by using mitomycin-C for a shorter period of time during trabeculectomy, performed in high risk glaucoma patients. Methods: Twenty eyes of patients of glaucoma, who were considered to be at high risk for failure because of their young age, previous ocular surgery like cataract extraction and trabeculectomy, inflammatory glaucoma, high myopia and prolonged anti-glaucoma medication, underwent trabeculectomy with topical application of 0.2mg/ml concentration of mitomycin C for three minutes. They were case matched with a group of same number of eyes of high risk glaucoma patients who received same concentration of drug for 5 minutes. Results: Twelve months after surg ery, the mean pre-operative IOP decreased from 29.9mmHg to a post-operative level of 16.05mmHg in 3 minutes group, with a success rate of 85%, and from 29.35mmHg to 16.55mmHg in 5 minutes group, with the same success rate of 85%. The incidence of complications was higher in 5 minutes group, when total number of complications was compared. ( p value< 0.05) Ocular hypotony developed in 3 (15%) eyes in 5 minutes group, and none in 3 minutes group. No patient developed hypotony related maculopathy in either group. Other complications like hyphema, post-operative uveitis, and conjunctival wound leakage were managed conservatively. Conclusion: The present study supports the conclusion of previous studies that mitomycin C is highly effective drug when used in association with trabeculectomy, and when used in concentration of 0.2mg/ml for three minutes is as effective in controlling post-operative IOP as is five minutes exposure time of the same concentration. Further, emphasizing that the shorter exposure of the drug is associated with lesser incidence of vision threatening complications.


2020 ◽  
Vol 1 (2) ◽  
pp. 122-127
Author(s):  
Kai-Yun Zhang ◽  

AIM: To investigate the effects of mitomycin C (MMC) on corneal endothelial cells at different exposure time during laser-assisted subepithelial keratomileusis (LASEK). METHODS: Patients who received LASEK were included and divided into Group T1 (15s≤t≤45s) and T2 (5s<t≤70s) based on the exposure time of MMC with corneal stroma. Cell density (CD) of corneal endothelial cells in central and peripheral cornea, average cell area (ACA), area standard deviation (SD), coefficient of variation (CV) and percentage of hexagonal cells (HEX) before surgery and at 1wk, 1, 3 and 6mo after surgery were compared between and within the groups. RESULTS: A total of 196 eyes of 98 patients were included with 98 eyes in Group T1 and 98 eyes in Group T2. With the exception of peripheral ACA, central CV and HEX in Group T1 and T2, which significantly changed at 1wk after the surgery (P<0.05), there was no significant difference in central and peripheral parameters within both groups or between the groups (P>0.05). CONCLUSION: Although transient acute changes in central CV and HEX and peripheral ACA were observed, there is no significant effect on the long-term corneal health status when MMC is applied in a reasonable time range in LASEK surgery.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Paul H. Sugarbaker ◽  
O. Anthony Stuart ◽  
Christopher Eger

In patients with pseudomyxoma peritonei or peritoneal mesothelioma, direct extension of disease through the hemidiaphragm may result in an isolated progression of tumor within the pleural space. We monitored the intrapleural and plasma levels of mitomycin C and doxorubicin by HPLC assay in order to determine the pharmacokinetic behavior of this intracavitary use of chemotherapy. Our results showed a persistent high concentration of intrapleural drug as compared to plasma concentrations. The increased exposure for mitomycin C was 96, and the increased exposure for doxorubicin was 241. When the clearance of chemotherapy from the thoracic cavity was compared to clearance from the abdomen and pelvis, there was a considerably more rapid clearance from the abdomen as compared to the thorax. The pharmacologic study of intrapleural chemotherapy in these patients provides a strong pharmacologic rationale for regional chemotherapy in this group of patients.


Chemotherapy ◽  
2005 ◽  
Vol 51 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Frank Meyer ◽  
Karsten Ridwelski ◽  
Thomas Gebauer ◽  
Reinhard Grote ◽  
Jens Martens-Lobenhoffer ◽  
...  

Author(s):  
F. A. Heckman ◽  
E. Redman ◽  
J.E. Connolly

In our initial publication on this subject1) we reported results demonstrating that contrast is the most important factor in producing the high image quality required for reliable image analysis. We also listed the factors which enhance contrast in order of the experimentally determined magnitude of their effect. The two most powerful factors affecting image contrast attainable with sheet film are beam intensity and KV. At that time we had only qualitative evidence for the ranking of enhancing factors. Later we carried out the densitometric measurements which led to the results outlined below.Meaningful evaluations of the cause-effect relationships among the considerable number of variables in preparing EM negatives depend on doing things in a systematic way, varying only one parameter at a time. Unless otherwise noted, we adhered to the following procedure evolved during our comprehensive study:Philips EM-300; 30μ objective aperature; magnification 7000- 12000X, exposure time 1 second, anti-contamination device operating.


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