| Background and objectiveBreast cancer is one of the most common malignant tumors which seriously threaten the health of women. The incidence and mortality of breast cancer are rank the first among the famale malignancy tumors. Especially in some economic flourishing regions and big city in our country, the incidence was resided the first female malignant tumor. Breast and thyroid belong to organs which are sensitive to pituitrin. The change of endocrine can leads to gland diseases. Breast cancer cells which still have normal function of hormone receptor grow depending on original hormones. Thyroid hormones promote the development and atomization of normal breast tissues. Thyroid hormones which can directly control the proliferation of cells change the metabolism of anterior pituitary, germen hormones and carcinogen by the shortage and excessive of its content.Thus, the thyroid hormones may promote the growth of tumor cells and also may suppress the development of tumor cells. Thyroid hormone receptor and Thyroid stimulating hormone receptor expresses in the breast tissues, estrogen effects developments physiology and pathology of thyroid. We discuss the relationship between breast cancer and thyroid diseases and realize whether thyroid diseases effect the progonosis of breast cancer.According to " The standard of efficacy of TCM sympotomes " pubished by State Administration of Traditional Chinese Medicine (ZY/T001.2-94), the sympotomes of breast cancer include three categories:Stagnation of liver-qi and accumulation of phlegm, Incoordination of the thoroughfare and conception vessels, Excessive toxin due to deficient qi. Thyroid diseases which belong to " goiter " in TCM is relevance of emotion, diet and natural enviroment and dimate. Stagnation of liver-qi, disharmony of the spleen, imbalance of zang-fu and retardent of meridians and collaterals which lead to qi stagnation, blood stasis and accumulation of phlegm which coagulate the neck. In addition, it is relevance with deficiency of liver and kidney and extrnal infection.The goiter and breast cancer are both relate to kidney, liver and spleen. Thus, they have the relevance in the pathogenesis of TCM theory. We discuss the distribution of breast cancer patients having thyroid diseases and further study thyroid diseases whether influenced its distribution.The sodium-iodide symporter (NIS) which is an integral membrane protein of thyroid follicular cells transports active iodide from vessels into cells through exchange Na+ and K+. It transports active iodide necessary for thyroid hormone synthesis. Accordingly, radioiodines are used for the diagnosis and treatment of various thyroid diseases. Most differentiated thyroid carcinomas retain NIS protein activity. This provides the basis for the use of radioiodine in the detection and therapy of thyroid cancer. Moreover, iodide also accumulates in the lactating mammary gland and is secreted into milk. Like thyroid cancers, it is possible that breast cancers express the NIS gene and protein. Several investigators have reported the expression of NIS protein and the NIS gene in various cases of human breast cancer. There is a possibility of being able to use NIS and radionuclide for the detection and treatment of breast cancer. Basal NIS gene expression is detected in about 85% breast cancer specimens, but the fraction with functional iodide transport is relatively low. The radioiodine is difficult to treat breast cancer. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in 'scan-negative'thyroid cancer and some breast cancer. Lactogenic hormones, estrogen, cAMP stimulus, glucocorticoid can stimulate NIS expression and increase radioiodide uptake.Thallus japonica which is Laminarin japonica Aresch has the effect of softening hardness to dissipate stagnation and disinhibiting water to draining heat. Thallus japonica is rich in iodide which maintains normal function of thyroid and breast tissue.It has lots of active ingredients which relate to its polysaccharide ingredients. Laminarin which is aβ-1,3 glucosan polymer can activate macrophagocyte and produce cytotoxicity in order to restrain the proliferati on of tumor cells. In addition, it can suppress tumor angiogenesis to control tumor growth. We research the effect of Laminarin to NIS gene and protein expression of MCF-7 cells and discuss the relationship between iodide uptake and NIS gene and protein expression.Part I The clinic research of the relationship between breast cancer and thyroid pathologyObjectiveThe aim of the study was to comfirm the incidence of the thyroid diseases among breast cancer patients and discuss whether thyroid diseases effect the prognosis of breast cancer patients.MethodsOur prospective open study was conducted on 100 consecutive patients operated for breast carcinoma. As a control group,100 individuals with normal breast examination, who did not have any known malignancy and/or thyroid disease, were included in the study. We aimed to identify the occurrence of thyroid pathologies, thyroid volume, the positive rate of TPOAb and TgAb and the number of TT3,TT4,FT3,FT4,TSH,TPOAb,TgAb in both groups to compare the ultrasound and the laboratory features of thyroid disease (TT3,TT4,FT3,FT4,TSH,TPOAb,TgAb) and breast carcinoma in an attempt to contribute to the studies investigating the relationship between these two entities.In addition,we also identified the pathology and biology features of breast cancer patients with/without thyroid diseases. We definited the baseline features such as age, menstruation and BMI of two groups.ResultsThe thyroid volumes of breast cancer patients and the control group did not differ significantly (P>0.05). When breast carcinoma patients were compared with the control group, thyroid pathology were found to be significa-ntly high in patients with breast cancer(62% vs 38%, P<0.05). There was no statistically significant difference between the two groups with respect to TPOAb,TgAb,TT3,TT4,FT3,FT4,TSH levels (P>0.05). Multiple nodular and nodular goiter thyroid pathologies were significantly higher in the breast cancer group when compared to the control group(P<0.05). There was no statistically significant difference between the two groups with respect to single nodular,adenoma cystadenoma, cystis thyroid pathologies and hyperthyroidism, hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, Hashimoto's thyroiditis(P>0.05). The incidence of TPOAb and TgAb positive are significantly higher in the breast cancer group when compared to the control group (P>0.05). In breast cancer patients with thyroid pathology, the incidence of HER-2 positive and Ki-67>30% were significantly more compared to the patients without thyroid disease(P<0.05). There was no significant relationship between other pathology features such as lymph nodes, the classification of histology, the stage of pathology, cancer embolus in vessel, progestational hormone receptor and estrogenic hormone receptor of the breast cancer patients and the presence of thyroid pathology (P>0.05). There was no statistically significant difference between the baseline features such as age, menstruation and BMI(P>0.05).ConclusionIn conclusion, the frequency of thyroid pathology is higher in breast cancer patients compared to controls indicating a relationship between breast carcinoma and thyroid pathology. Our study shows that breast cancer patients accompany with thyroid morphology changes such as multiple nodular and nodular goiter. The incidence of TPOAb and TgAb positive are significant-ly higher in the breast cancer group, it is indicated that breast cancer may be relevance to autoimmune thyroid diseases. Although the incidence of HER-2 positive and Ki-67>30% are higher in breast cancer patients with thyroid thyroid pathology, there was no significant relationship between other pathology features such as lymph nodes, the classification of histolog-y, the stage of pathology, cancer embolus in vessel, progestational hormone receptor and estrogenic hormone receptor of the breast cancer patients and the presence of thyroid pathology, we need further studies are needed to investigate the prognosis and survival of breast cancer patients in the presence of thyroid pathology. PartⅡResearch on the d i str i but i on of TCM syndromes i n breast cancer patients with thyroid pathology Object iveTo study the distribution of TCM syndromes in breast cancer patients with thyroid pathology and disscuss thyroid pathology whether influences the the distribution of TCM syndromes in breast cancer. MethodsWhen breast cancer patients were hospitalized, the questionnaire was written in time. Through satatistic analysis, it is confirmed that the distribution of TCM syndromes in breast cancer patients with thyroid pathology and control group. ResultsIn breast cancer patients with thyroid pathology, Stagnation of liver-qi and deficiency of spleen occupied 50%, deficiency of kidney-yin occupied 19.35%, blood stasis occupied 16.13%, deficiency of kidney-yang occupied 14.52%. In the control group, Stagnation of liver-qi and deficiency of spleen occupied 57.89%, deficiency of kidney-yin occupied 10.53%, blood stasis occupied 21.05%, deficiency of kidney-yang occupied 10.53%. There was no statistically significant difference between the two groups with respect to the distribution and the grading numbers of TCM syndromes (P>0.05).ConclusionThyroid pathology did not effect the distribution of TCM syndromes in breast cancer patients. There was no statistically significant difference between the two groups with respect to the grading numbers of TCM syndromes.PartⅢThe effect of Laminar in on the expression of NIS gene and protein expression and rate of iodide uptake in breast cell(MCF-7).ObjectiveTo investigate the effect of Laminarin on the expression of gene and protein of NIS and the relationship between NIS expression and the ability of iodide uptake in breast cancer cell.MethodsThe breast cancer cell line(MCF-7) was cultured with different concentrations of Laminarin(0, 10ug/mL,50ug/mL,100ug/mL,200ug/mL). NTS mRNA and protein in cultured breast cancer cells was determined by Real-time PCR and Western blot after 24h,48h,72h. The activity of iodide uptake was determined by 125I uptake rate. ResultsWhen compared with blank control group, NIS gene expression and prote in expression were enhanced by Laminarin in dose-dependent manner after s timulating 24h (P<0.05). There was no statistically significant differen ce between 100ug/ml and 200ug/ml after stimulating 24h(P>0.05). Compared among other groups, they all have statistically significant diffe rence (P<0.05). When compared with blank control group, NIS gene expressi on and protein expression were enhanced by Laminarin in dose-dependent ma nner after stimulating 48h(P<0.05). Compared among groups, they allhave st atistically significant difference (P<0.05). When compared withblank cont rol group, NIS gene expression and protein expression were enh-anced by La minarin in dose-dependent manner after stimulating 72h(P<0.05). There was no statistically significant difference between 100ug/ml and 200ug/ml af ter stimulating 72h(P>0.05). Compared among other groups, they all have st atistically significant difference(P<0.05). The activity of iodide uptak e had been found to be increased by Laminarin in dose-dependent manner(P <0.05). There was no statistically significant diffe-rence between Oug/ml and 10ug/ml (P>0.05).ConclusionNIS gene expression and protein expression were enhanced by Laminari-n in dose-dependent manner. The activity of iodide uptake had been found to be increased by Laminarin which may be attribute to enhance the NIS gene experessin and protein expression.
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