雌激素、孕激素在妊娠期银屑病中的作用研究进展

银屑病是一种T细胞介导的人类自身免疫性炎症性疾病,与辅助性T细胞1型(Th1)细胞因子的过度表达和Th2细胞因子的相对表达不足有关,其特征是Th1和Th17细胞在全身或局部表达水平增加。研究表明,约55%的妊娠期银屑病患者有所改善,雌二醇是最强效的天然雌激素,雌激素水平的增加,尤其是相对于孕酮的雌激素水平的增加,与银屑病的好转相关。相比之下,当雌激素和孕酮水平在产后、月经前、月经后和停经时下降,则有银屑病病情恶化的报告。妊娠期雌激素、孕激素水平的变化可以促进Th2细胞的分化,相应的抑制Th1细胞的分化,同时抑制Th17细胞的表达,促进调节性T细胞的表达。进而减轻银屑病症状,该文对雌激素、孕激素在妊娠期银屑病中的作用研究进展作一综述。

Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma

AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specif ic antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.

Ki-67 as a prognostic marker according to breast cancer molecular subtype

Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.

术前针刺活检与手术标本分类的一致性对早期乳腺癌治疗的影响

目的探讨术前针刺活检与手术标本分类的一致性对早期乳腺癌治疗的影响。方法以我院48例接受手术的乳腺肿瘤患者作研究对象,上述患者均接受穿刺活检和手术切除活检,以手术切除活检为标准,分析穿刺组织ER、PR、HER2和Ki-67免疫组化检测结果。结果手术切除确诊42例阳性,6例阴性,穿刺组织ER、PR、HER2和Ki-67的,阳性预测值97.44%、93.75%、89.65%和92.59%,阴性预测值55.56%、25%、15.79%和19.05%,敏感度92.86%、71.43%、61.91%和47.62%,特异度75%、33.33%、27.27%和21.43%。结论穿刺活检ER、PR、HER2和Ki-67免疫组化联合检测比较准确反映乳腺癌组织病理情况,为该病的治疗提供参考。

Treatment for triple-negative breast cancer

Triple-negative breast cancers (TNBCs) neither express estrogen receptor and progesterone receptor nor over- express human epidermal growth factor receptor-2. Because of the special molecular features, triple-negative breast cancer is not either sensitive to endocrine therapy or targeted therapy of trastuzumab. There has not been standard treatment regimen for triple-negative breast cancer yet and chemotherapy has still been the chief therapy currently. However, with the great progress of oncology and molecular biology, the understanding of the natural history, pathophysiology and molecular features of this disease has been greatly improved, and a growing number of novel and effective therapies and discoveries of new biological targets for this phenotype of breast cancers have been reported, which provide new insights into therapeutic strategies for the women suffering from it.

Effects of Fuke Qianjin Formula on hormones and their receptors and metabonomics study in uterine fibroids model rats

Objective To investigate the effects of different fractions from Fuke Qianjin Formula(妇科千金方,FKQJF)on uterine leiomyoma(UL)to determine the best fraction.Methods FKQJF was extracted and isolated to obtain polysaccharides(FKP),flavonoids(FKF),and grease(FKG).140 female SPF SD rats were divided into 14 groups[model(MOD),normal control(NC),Gouliuqing(GLQ),Mifepristone(MFST),FKQJF,low,medium,and high dose of polysaccharides(l-FKP,m-FKP,and h-FKP),low,medium,and high dose of flavonoids(l-FKF,m-FKF,and h-FKF),low,medium,and high dose of grease(l-FKG,m-FKG,and h-FKG)],and uterine fibroids model rats were treated with drugs for four weeks.Serum levels of estrogen and progesterone were measured using enzyme-linked immunoassay assay(ELISA)kits.The expression of estrogen receptor(ER-α,ER-β)and progesterone receptor(PR)in the uterus was observed using immunohistochemistry(IHC).Serum metabolite profiles and FKG were analyzed using gas chromatography-mass spectrometry(GC-MS).Results FKQJF,h-FKF,m-FKG,and h-FKG significantly downregulated the estrogen level in the uterine fibroid model rats(P<0.01).FKQJF,h-FKF,and h-FKG significantly reduced the level of progesterone in the uterine fibroid model rats(P<0.01).The levels of ER-α,ER-β,and PR in uterine fibroid model rats were significantly decreased by FKQJF and h-FKG(P<0.01).The levels of ER-α,ER-β,and PR in the fibroid model rats were decreased by m-FKG(P<0.05).Additionally,serum metabolism results revealed that h-FKG and FKQJF could regulate related endogenous metabolites and make the pathological indices of uterine fibroids in rats close to the normal group.Forty-six components were identified in the oil,accounting for 91.97%of the total oil components.Conclusion FKQJF and h-FKG showed a significant anti-myoma activity and significantly improved the pathological state of the uterus in rats with hysteromyoma.The mechanism of action may be related to the regulation of estrogen progesterone and its receptor in uterine fibroid model animals.These findings proved the effect of FKQJF on uterine leiomyoma and provided an experimental basis for its clinical research and application.

Clinico-pathological significance of extra-nodal spread in special types of breast cancer

Objective: To investigate the significance of extra-nodal spread in special histological sub-types of breast cancer and the relationship of such spread with prognostic parameters.Methods: A total of 303 breast cancer cases were classified according to tumor type, and each tumor group was subdivided according to age, tumor diameter, lymph node metastasis, extra-nodal spread, vein invasion in the adjacent soft tissue, distant metastasis, and immunohistochemical characteristics [estrogen receptor(ER), progesterone receptor(PR) existence, p53, c-erbB-2, and proliferative rate(Ki-67)]. The 122 cases with extra-nodal spread were clinically followed up.Results: An extra-nodal spread was observed in 40%(122 cases) of the 303 breast cancer cases. The spread most frequently presented in micro papillary carcinoma histological sub-type(40 cases, 75%), but least frequently presents in mucinous carcinoma(2 cases, 8%). Patients with extra-nodal spread had a high average number of metastatic lymph nodes(8.3) and a high distant metastasis rate(38 cases, 31%) compared with patients without extra-nodal spread.Conclusion: The existence of extra-nodal spread in the examined breast cancer sub-types has predictive value in forecasting the number of metastatic lymph nodes and the disease prognosis.

Effects of Estradiol on 5-HTsA and 5-HT2c Receptor Immunolabeling in Rat Hippocampus

Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A and 5-HT2c immunolabeling induced by steroids in the hippocampus ofovariectomized rats were studied in this work. Densitometric analysis in rat hippocampi were carried out for adjacent brain coronal immunolabeled sections after treatment with subcutaneous injections of vehicle, estradiol, progesterone or the combination of both steroids in ovariectomized rats. Exposure to estradiol and the combination of estradiol and progesterone significantly reduced the 5-HT5A-like immunosignal in the CA 1 region while progesterone did not induce changes. On the other hand, exposure to the combination of estradiol and progesterone or estradiol alone increased the 5-HT2c immunosignal in the same region. These results indicate that estradiol is involved in the discrete regulation of serotonin receptors 5-HT5A and 5-HT2c in rat hippocampus.

Relationship between expression of ER, PR, Her-2, Ki-67 and neoadjuvant chemotherapy effect in breast cancer

Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.

Expression of BI-1 protein and its significance in breast cancer

Objective： To investigate the correlations of expression of Bax inhibitor-1 （BI-1） gene and the receptors of estrogen and progestogen in breast cancer and its significance. Methods： Immunohistochemical methods had been used to detect the expressions of BI-1 gene and receptors of estrogen and progestogen in breast cancer. Results： The positive rates of expressions of BI-1 gene, estrogen receptor （ER） and progestogen receptor （PR） in breast cancer were 77.08%, 60.42% and 54.17%, respectively. The positive rate of expression of BI-1 gene was higher in the group with negative expression of ER than the positive group, their positive rates were 76.92% and 52.27%, respectively; but there was no statistical difference between the two groups with positive and negative expressions of PR. The positive rate of expression of BI-1 gene was also higher in the group with positive lymph node metastasis than the non-lymph node metastasis group, and their positive rates were 64.58% and 36.36%, respectively. The difference was statistically significant （P 〈 0.05）. Conclusion： BI-1 gene, in combination with ER, has guiding significance for patients with breast cancer to choose individual chemotherapy and radiotherapy after operation and can become an important indicator for judging the prognosis of breast cancer.

浸润性乳腺癌HER-2蛋白过表达人群中ER、PR的表达及与HER-2基因扩增之间的相关性

目的探讨浸润性乳腺癌人表皮生长因子受体-2(HER-2)蛋白及雌激素受体(ER)、孕激素受体(PR)的表达情况,并研究HER-2基因扩增与ER、PR、HER-2蛋白表达之间的关系。方法采用免疫组织化学(SP)法和荧光标记原位杂交(FISH)法检测60例浸润性乳腺癌患者HER-2蛋白、ER、PR的表达及乳腺癌中HER-2基因扩增情况。结果 60例乳腺癌组织中出现HER-2基因扩增23例,阳性率为38.33%,ER、PR蛋白的阳性表达分别为31例、34例,HER-2基因扩增在ER、PR蛋白阳性时分别低于阴性时,差异有统计学意义(P<0.05);HER-2基因扩增在ER、PR蛋白分别为阳性、阴性时与ER、PR蛋白分别为阴性、阳性时相比差异无统计学意义(P>0.05),在ER、PR蛋白同时为阳性时低于同时为阴性时,差异有统计学意义(P<0.05)。结论浸润性乳腺癌HER-2蛋白过表达人群中ER、PR的表达与HER-2基因扩增之间存在相关性。