| ObjectiveIn this research were tested the concentration,proliferation,and apoptosis of paclitaxel in the pelvic and abdominal lymph nodes of SD rats and the patients with endometrial cancer after they are injected with paclitaxel-nanocarbon mixed suspension(PA-CH)in different sites at the same time and with the same dosage.By such tests,explorations were concentrated on the best injecting site of PA-CH and the function mechanism and efficacy of nanocarbon mixed suspension absorbing paclitaxel(a drug used for chemotherapy).The investigation may own the potential to provide a new,optional treatment of better safety and effectiveness for the patients who possibly suffer from endometrial cancer with lymph node metastasis.MethodPart ?.Animal ExperimentTwenty SD rats(female rats)were randomly divided into two groups:group A(n=4):paclitaxel 1 mg was injected submucous into the cervix of rats,and group A(n=4)was treated with paclitaxel 1 mg by submucous injection of paclitaxel.Group B(n=16):through cervical submucous membrane of 8 rats(4 rats were given for 6 hours,the other 4 rats were given for 24 hours),and the right soles of the foot(4 rats)weregiven to the cervical submucous membrane(8 rats,4 rats)and the right foot soles(4rats),respectively.Paclitaxel-nano-carbon suspension 0.217ml(lmg paclitaxel 0.5ml nanocarbon)was injected into abdominal cavity(n=4).The rats in cervical group,right foot group and abdominal cavity group were killed 6 hours after administration.Black staining lymph nodes were collected and the concentration of paclitaxel in pelvic and abdominal lymph nodes of rats with different administration sites was detected by LC-MS method.In the cervical test group,24 hours after administration,the black-stained lymph nodes of the rats were collected and the expression of Ki67gene and CL-caspase3 gene were detected by immunohistochemical(IHC)staining.Part ?.Clinical Experiment48 cases of patients undergoing staging surgery for endometrial cancer in the Department of Gynecology,Fourth Affiliated Hospital of Kunming Medical University have been acquired from March 2018 to March 2019.Those 48 patients were evenly divided into three groups.The first group was set as a blank control group.The patients in this group were given at the neck of uterus 1.0ml of nanocarbon+2ml of physiological saline during the operation.Both the second and third groups were labeled as tested groups.They were treated in the operation with two different delivering routes of drug,trans-cervix administration and trans-uterus administration,respectively,and injected with the same dosage of PA-CH(20mg of paclitaxel?1.0ml of nanocarbons+2ml of physiological saline).Comparisons were conducted between the distribution of paclitaxel concentration and cell proliferation and apoptosis in the pelvic and abdominal lymph nodes and tissues at the same dosage and administration time and by different routes of administration.Thereupon,the discussion on the most ideal site for PA-CH injection in the patients with endometrial cancer was next carried out.ResultsPart ?.Animal Experiment1.Comparison of paclitaxel concentration in lymph node tissue betweenexperimental groups and control group at the same medication time and by the same administration route.Compared with the right foot group,the concentration of paclitaxel in the lymph nodes of the cervical group was similar to that of the right foot group(4171.99±1976.55 VS 2478.03±505.53,P>0.05).The concentration ofpaclitaxel in lymph nodes of cervical group and right foot group was higher than that of abdominal cavity group(P<0.05).2.After 6 hours of cervical administration in rats,paclitaxel was loaded with nano-carbon or not.Comparison of paclitaxel concentration in rat lymph nodes:the concentration of paclitaxel in lymph nodes of rats with paclitaxel loaded with nano-carbon was higher than that without carbon nanoparticles(4171.99±1976.55 VS 2467.39 ±211.92,p<0.05).3.Compared with the same administration site,the same administration dose,the different administration time,the proliferation and the apoptosis of the lymph node cells in the rat:the same dose of the chemotherapy drug was administered through the cervix,and the proliferation of the lymph nodes in the rat after 24 h was lower than 6 hours(13.75)4.79 VS 46.25 to 4.78,After 24 h,the apoptosis of the lymph nodes was higher than that of 6 h(57.50,6.45 VS 22.50,6.45,p<0.05).Part ?.Clinical Experiment1.By intracervical administration,compare the differences in drug concentration between the tested group and the control group.the concentration of paclitaxel in cervical group(pelvic,common ilium)lymph nodes was higher than that in the corresponding control group(p<0.05).The concentration of paclitaxel in cervical lymph nodes was similar to that in uterine body group(2358.30±649.30 VS 2161.83±967.36,p>0.05).The concentration of paclitaxel in common ilium lymph nodes in uterine body group was higher than that in cervical group(1654.0311±446.68 VS 954.5379±385.83,p<0.05).2.Regard different drug delivery routes to lymph nodes in the same site,compare the differences in drug concentration between the tested groups.In the experimental group,the concentration of paclitaxel in pelvic black-stained lymph nodes was higher than that in non-black-stained lymph nodes(p<0.05),and in the experimental group,the concentration of paclitaxel in pelvic black-stained lymph nodes was higher than that in surrounding adipose tissue(p<0.05).3.Regard the same drug administration route to tissues(black-stained lymph nodes,un-stained lymph nodes,adipose tissue)at different sites,compare the drug concentration in these sites.For the by-uterus administration and by-cervix administration,the black-stained lymph nodes and the unstained lymph nodes of the tissue at the same site were compared and the difference in the paclitaxel concentration between them is statistically significant(p<0.05).Similarly,the difference in the paclitaxel concentration between the black-stained lymph nodes and the surrounding adipose tissue is also statistically significant(p<0.05).ConclusionAnimal Experiment1.The nanocarbon mixed suspension can be loaded with paclitaxel(a chemotherapy drug)and deliver it specifically toward the lymph nodes of rats.Such a targeting action significantly increases the drug concentration of paclitaxel in the lymph nodes.2.The concentration of paclitaxel in lymph nodes was similar through cervix,right foot,abdominal cavity and three different administration sites,but the concentration of paclitaxel in lymph nodes was higher than that in abdominal cavity of rats.3.The intraperitoneal administration in rats renders a lower paclitaxel concentration in the lymph nodes.The nanocarbon loaded with paclitaxel meets a difficulty in penetrating the peritoneum and bring the drug to the ymph nodes of the rat.4.Intracervical administration.Compared with the result at 6 hours after the administration,the result at 24h presents a declination in the intensity of ki-67 expression in the rats' lymphocytes while an enhancement in the CL-caspase3 expression.That is to say,the proliferation of lymphocytes has been suppressed and their apoptosis has increased.Clinical Experiment1.The nanocarbon mixed suspension is able to load paclitaxel specifically into the lymph nodes in the tumor drainage region.2.Among pelvic blacked-stained lymph nodes,no significant difference was found between the paclitaxel concentrations after an administration by the cervix and the uterus.Among common iliac lymph nodes,however,the paclitaxel concentration resulted from by-uterus administration is shown higher than that from by-cervical administration.3.The administration routes through uterus and cervix both lead to higher concentrations of paclitaxel in the blacked-stained lymph nodes than that in the non-blacked-stained lymph nodes and peripheral adipose tissue.Equipped with high tropism to the lymphatic system,the nanocarbon mixed suspension is thus allowed to direct the paclitaxel specifically into the lymph nodes.4.Drug administrations via the uterus or cervix were made 1 hour after an intraoperative administration.Between the control group and tested groups,or between the tested groups,no significant statistic differences were obtained from the expressions of ki-67 and CL-caspase3 in the pelvic or common iliac lymph nodes.5.In cervical group,age,pregnancy and delivery,tumor size,pathological grade and tumor stage were not correlated with paclitaxel concentration in pelvic and abdominal lymph nodes. |
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