犬阴道肿瘤与主要生殖激素及端粒酶活性关系的研究
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摘要
本研究应用放射免疫分析法测定正常犬与我院临床收治的阴道肿瘤患犬不同发情周期血浆主要生殖激素水平的变化,应用免疫组化SP法检测特定时期上述肿瘤及正常阴道组织内雌、孕激素受体(ER、PR)的表达,及应用改进的TRAP-银染法检测了它们的端粒酶活性。实验结果显示阴道增生患犬发情前期雌二醇水平明显升高,说明阴道增生的发生、发展与血浆雌二醇水平有很大关系;母犬感染TVT后会引起内分泌失调,雌、孕受体在CTVT组织中表达缺失,还发现CTVT始终保持着较低的端粒酶活性,但消退期比生长期的肿瘤端粒酶活性更低。腺泡状软组织肉瘤ERα表达阳性,PR表达阴性,说明犬阴道腺泡状软组织肉瘤为雌激素依赖性肿瘤。研究结果为肿瘤的预后和治疗提供了新的依据。
The morbidity of vaginal tumors in dogs is rising year by year along with our country’s house pet rapid development which made the canine appearance and productivity be seriously affected. Nevertheless, the generation of canine vaginal tumors is complex and various relatively. People were still not well understand it although they were studying about these canine vaginal tumors all the time. So the theory about prognosis and treatment of tumors are insufficient as so far .And the original method of treatment are requested urgently because drug resistance has been observed in some cases such as the treatment of CTVT. Now, it’s be found that endocrine therapy is special and convenient and restrain telomerase activity of cancers used to obtain accurate treatment has already become a hot spot;these two methods have broad application prospects in the treatment of cancer.
In this study,the canine vaginal tumors including 38 exmples and collected from clinics were divided into three types:the vaginal hyperplasy, the transmissible venereal tumor (CTVT) and the alveolar soft part sarcoma (ASPS) based on clinical observations and the detailed histopathologic features of variants. we assembled some datas regarding the age,time and path of canine tumorigenesis, and whether the tumours disappear by themselves or not. Form the data we found some regular features: the vaginal hyperplasy always happened in proestrus and estrus for the first oestrous cycle. The vaginal hyperplasy keep on growing along with estrus continuing.Someones can be disappear by themselves.The dogs infected by TVT can accept to mate,but be unable to conceive, ASPS usually has happened on different locus of vaginal wall for several times. Basing on the datas above-mentioned ,we speculated that there is an association between reproductive hormones and canine vaginal tumors extraordinary behavior.
On present study, we determined estrogen receptor (ER-a) and progesterone receptor(PR) expression in three species of vaginal neoplastic tissues by the means of immunohistochemical SP, and measured serum concentrations of major reproductive hormones by radioimmunoassay. The objective of this study was to find an association between major reproductive hormones and canine vaginal tumors behavior which can provide new theory basis for diagnosing and treating vaginal tumors
The result showed that the serum concentrations of estrogen from the dogs which suffered from vaginal hyperplasy in proestrum were much higher compared with control group, and the peak value of FSH appeared ahead of schedule time . As a result, we infered that there was an significant association between serum concentrations of reproductive hormones and canine vaginal tumors behavior. Whereas the quantity of ER-a expression in neoplastic tissues didn’t increase compared t with control group. we knew fom previous studys .It has been confirmed that there are not a noticeable relation between the quantity of ER-a receptors expression in vascular endothelial cell , smooth muscle cell and matrix fiber cell and serum concentrations of estrogen ,but it’s a opposite result to ER-βreceptors expression .The detailed histopathologic features was that the hyperplastic tissue contains plents of vascular endothelial cell and smooth muscle cell ,so we suspected that the raise of serum concentrations of estrogen result in increasing of the quantity of ER-βreceptors expresion.Accordingly, physiological functions of estrogen was increasing, and then lead to the proliferation of vaginal wall
The serum concentrations of progesterone from dogs affected by TVT were lower obviously than control group during estrus and diestrus;and the serum concentrations should increase in diestrus comparing to estrus but not ;at the same time, LH had a higher but E2 a lower serum concentration during diestrus; perhaps this findings could explain that why the dogs affected by TVT was able to accept to mate but not conceive.In this study ,we found yet that ER-a and PR expression were not present in CTVT cell. Perhaps“alteration theory”could explain this phenomenon. The unique aspect of the TVT is that it does not arise from mutant or undifferentiated vaginal cells; instead, it is transmitted through the deposition of neoplastic cells from affected tissue on to tissue that has been subjected to trauma.And CTVT most likely originated from a wolf or an East Asian breed of dog between 200 and 2500 years ago .This could, in part explain the lack of receptor.
The serum concentrations of estrogen and progesterone from dogs having vaginal ASPS change not obviously during diestrus,whereas the tumor were highly positive for ER-a which indicate that it’s hormonal dependent tumour and it will have good responses to hormone therapy In present research we we evaluated telomerase activity in three species of canine vaginal tumors with modified TRAP technique and the Bandscan software. It was found that CTVT cells from the progressive phase (P-phase) and regress phase (R-phase) were both positive for telomerase activity, although it was lower in the R-phase.We detected yet that ASPS had not any telomerase activity,but histopatho- logic features illustrated it was malignancy;it maybe that the quantity of this tissue was so scarce in the samples collected that the presence of telomerase activity in ASPS tissue could not be assessed because of some reasons such as incorrect operation;we had not found some examples had tumor metastasis clinically and the reports about these examples were insufficient; so we need much more observation and research to evaluated the tumour whether tumor metastasis or not.
In a word, we had determined serum concentrations of major reproductive hormone, evaluated ER-α,PR expressions and telomerase activity in the tumours tissue.The objective of this study was to search simplely for pathogenesy of canine vaginal tumor and provide new theory for diagnosis and treatment due to limitation of clinical condition, we could not assesse some aspects, for instance, we could determine (immunohisto- chemically) (ER-a)and PR expression in vaginal tissue of healthy bitches and in the vaginal a tissues of tumours-affected bitches, evaluate ER-βexpressions in tumours, and evaluate telomerase activity in ASPS tours when there’re many exemples from clinic. In order to understand these tumours much more, So the next step we will study these aspects
The morbidity of vaginal tumors in dogs is rising year by year along with our country’s house pet rapid development which made the canine appearance and productivity be seriously affected. Nevertheless, the generation of canine vaginal tumors is complex and various relatively. People were still not well understand it although they were studying about these canine vaginal tumors all the time. So the theory about prognosis and treatment of tumors are insufficient as so far .And the original method of treatment are requested urgently because drug resistance has been observed in some cases such as the treatment of CTVT. Now, it’s be found that endocrine therapy is special and convenient and restrain telomerase activity of cancers used to obtain accurate treatment has already become a hot spot;these two methods have broad application prospects in the treatment of cancer.
In this study,the canine vaginal tumors including 38 exmples and collected from clinics were divided into three types:the vaginal hyperplasy, the transmissible venereal tumor (CTVT) and the alveolar soft part sarcoma (ASPS) based on clinical observations and the detailed histopathologic features of variants. we assembled some datas regarding the age,time and path of canine tumorigenesis, and whether the tumours disappear by themselves or not. Form the data we found some regular features: the vaginal hyperplasy always happened in proestrus and estrus for the first oestrous cycle. The vaginal hyperplasy keep on growing along with estrus continuing.Someones can be disappear by themselves.The dogs infected by TVT can accept to mate,but be unable to conceive, ASPS usually has happened on different locus of vaginal wall for several times. Basing on the datas above-mentioned ,we speculated that there is an association between reproductive hormones and canine vaginal tumors extraordinary behavior.
On present study, we determined estrogen receptor (ER-a) and progesterone receptor(PR) expression in three species of vaginal neoplastic tissues by the means of immunohistochemical SP, and measured serum concentrations of major reproductive hormones by radioimmunoassay. The objective of this study was to find an association between major reproductive hormones and canine vaginal tumors behavior which can provide new theory basis for diagnosing and treating vaginal tumors
The result showed that the serum concentrations of estrogen from the dogs which suffered from vaginal hyperplasy in proestrum were much higher compared with control group, and the peak value of FSH appeared ahead of schedule time . As a result, we infered that there was an significant association between serum concentrations of reproductive hormones and canine vaginal tumors behavior. Whereas the quantity of ER-a expression in neoplastic tissues didn’t increase compared t with control group. we knew fom previous studys .It has been confirmed that there are not a noticeable relation between the quantity of ER-a receptors expression in vascular endothelial cell , smooth muscle cell and matrix fiber cell and serum concentrations of estrogen ,but it’s a opposite result to ER-βreceptors expression .The detailed histopathologic features was that the hyperplastic tissue contains plents of vascular endothelial cell and smooth muscle cell ,so we suspected that the raise of serum concentrations of estrogen result in increasing of the quantity of ER-βreceptors expresion.Accordingly, physiological functions of estrogen was increasing, and then lead to the proliferation of vaginal wall
The serum concentrations of progesterone from dogs affected by TVT were lower obviously than control group during estrus and diestrus;and the serum concentrations should increase in diestrus comparing to estrus but not ;at the same time, LH had a higher but E2 a lower serum concentration during diestrus; perhaps this findings could explain that why the dogs affected by TVT was able to accept to mate but not conceive.In this study ,we found yet that ER-a and PR expression were not present in CTVT cell. Perhaps“alteration theory”could explain this phenomenon. The unique aspect of the TVT is that it does not arise from mutant or undifferentiated vaginal cells; instead, it is transmitted through the deposition of neoplastic cells from affected tissue on to tissue that has been subjected to trauma.And CTVT most likely originated from a wolf or an East Asian breed of dog between 200 and 2500 years ago .This could, in part explain the lack of receptor.
The serum concentrations of estrogen and progesterone from dogs having vaginal ASPS change not obviously during diestrus,whereas the tumor were highly positive for ER-a which indicate that it’s hormonal dependent tumour and it will have good responses to hormone therapy In present research we we evaluated telomerase activity in three species of canine vaginal tumors with modified TRAP technique and the Bandscan software. It was found that CTVT cells from the progressive phase (P-phase) and regress phase (R-phase) were both positive for telomerase activity, although it was lower in the R-phase.We detected yet that ASPS had not any telomerase activity,but histopatho- logic features illustrated it was malignancy;it maybe that the quantity of this tissue was so scarce in the samples collected that the presence of telomerase activity in ASPS tissue could not be assessed because of some reasons such as incorrect operation;we had not found some examples had tumor metastasis clinically and the reports about these examples were insufficient; so we need much more observation and research to evaluated the tumour whether tumor metastasis or not.
In a word, we had determined serum concentrations of major reproductive hormone, evaluated ER-α,PR expressions and telomerase activity in the tumours tissue.The objective of this study was to search simplely for pathogenesy of canine vaginal tumor and provide new theory for diagnosis and treatment due to limitation of clinical condition, we could not assesse some aspects, for instance, we could determine (immunohisto- chemically) (ER-a)and PR expression in vaginal tissue of healthy bitches and in the vaginal a tissues of tumours-affected bitches, evaluate ER-βexpressions in tumours, and evaluate telomerase activity in ASPS tours when there’re many exemples from clinic. In order to understand these tumours much more, So the next step we will study these aspects
引文
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