Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.
Objective: Both estrogen receptors, ER alpha ($ER{\alpha}$) and ER beta ($ER{\beta}$), are expressed in 50-70% of breast cancer cases. The role of $ER{\alpha}$ as a prognostic marker in breast cancer has been well established as its expression is negative correlated with tumor size and lymph node metastasis. $ER{\beta}$ is also a favorable prognostic predictor although this is less well documented than for $ER{\alpha}$. Materials and Methods: To explore whether ERs independently or together might influence clinical outcome in breast cancer, the correlation between the ERs with the clinicopathological features was analyzed in 84 patients. Results: $ER{\alpha}$ expression negatively correlated with tumor stage (r=-0.246, p=0.028) and tended to be negatively correlated with lymph node status (r=-0.156, p=0.168) and tumor size (r=-0.246, p=0.099). Also, $ER{\beta}$ was negatively correlated with nodal status (r=-0.243, p=0.028), as was coexpression of $ER{\alpha}$ and $ER{\beta}$ (p=0.043, OR=0.194, 95% CI= 0.040-0.953). Conclusion: Coexpression of ERs might serve as an indicator of good prognosis in breast cancer patients.
Normal and abnormal follicular growth and steroidogenesis depend on gonadotropins as well as intraovarian peptides, which may mediate or potentiate gonadotropin action. Inhibin also affect follicular development and steroidogenesis and may play a role in dominant follicle selection and follicular atresia. Therefore, we studied the differences of serum inhibin, gonadotropin and androgen levels in the women with only the ultrasound findings and no disorder, and polycystic ovary (PCO) with ovulatory disturbance. We prospectively analysed forty-three women with PCO. The diagnosis of PCO was based on typical appearance of the ovaries on TVS. Twelve women with regular menstrual cycle and normal ovarian morphology were selected as control. Basal levels of inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol $(E_2)$, testosterone (T), androstenedione (ADD), dehydroepiandrosterone-sulfate (DS), prolactin and TSH in serum were determined. There were significant differences in basal LH levels and LH/FSH ratio between the control and the women with PCO. The basal levels of inhibin and $E_2$ in the oligo-amenorrheic PCO (N=34) were significantly higher than those in the control. There was higher negative correlation between the inhibin and T levels in the oligo-amenorrheic PCO, but, not in the regular cycling PCO. Also, there was higher positive correlation between the LH and T levels in the oligo-amenorrheic PCO, but not in the regular cycling PCO. These data presume that the initial event of PCO is elevated pituitary LH secretion. Elevated levels of LH may down-regulate LH receptors on granulosa cells and also cause hypertrophy of the thecal layer. High level of androgen secreted by the hypertrophied thecal layer may stimulate inhibin secretion from granulosa cells and can be converted to estrogen by extraovarian tissues and could serve to augment pituitary sensitivity to GnRH with a resultant secretion of more LH than FSH. Inhibin may inhibit FSH action on granulosa cell in the PCO follicle, impairing follicular development and dominant follicle selection resulted in ovulatory disturbance.
Objectives : Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density and increased risk of fractures. Bisphosphonates and selective estrogen receptors, which are bone resorption inhibitors that are currently widely used as osteoporosis treatments, show serious side effects when administered for a long time. Research on bone resorption inhibitors that complement the problems of existing treatments is needed. The purpose of this study was to investigate the effect of inhibiting osteoclast differentiation and activity on the tuberous root of Ampelopsis japonica (Thunb.) Makino (AM). Methods : After extracting AM using distilled water and ethanol, the inhibitory effects of the two solvents on osteoclast differentiation were compared using the RANKL-induced in vitro experimental model and the TRAP assay kit. The impact of AM on bone resorption was investigated through the pit formation assay, and its effect on F-actin formation was assessed through fluorescent staining. Additionally, protein and mRNA expression levels of osteoclast differentiation markers (NFATc1, c-Fos, TRAP and ATP6v0d2) and resorption markers (MMP-9, CTK, and CA2) were analyzed via western blot and RT-PCR. Results : AM treatment significantly decreased the number of TRAP-positive cells and pit formation area. Furthermore, AM suppressed both the protein and mRNA expression of NFATc1 and c-Fos, key transcription factors involved in osteoclast differentiation and it downregulated the expression of osteoclast-associated genes such as TRAP, CTK, MMP-9, CA2, and ATP6v0d2. Conclusions : These results suggest that AM can inhibit bone resorption and osteoclast differentiation, indicating its potential for use in the treatment and prevention of osteoporosis.
Park, Yoon-Kee;Lee, Sung-Ho;Kwon, Oh-Cheol;Ha, Jeoung-Hee;Lee, Kwang-Youn;Kim, Won-Joon
Journal of Yeungnam Medical Science
/
v.9
no.2
/
pp.359-381
/
1992
This study was designed to investigate the effect of diazepam on the spontaneous contraction and oxytocin induced contraction of the isolated rat uterus. Female rat(Sprague-Dawley) pretreated with oophorectomy and 4 days administration of estrogen, weighing about 200 g, was sacrificed by cervical dislocation, and the uteruses were isolated. A longitudinal muscle strip was placed in temperature controlled($37^{\circ}C$) muscle chamber containing Locke's solution and myographied isometrically. Diazepam inhibited the spontaneous contraction and oxytocin induced contraction of the isolated rat uterus in a concentration-dependent manner. GABA, muscimol, a GABA A receptor agonist, bicuculline, a competitive GAGA A receptor antagonist, picrotoxin, a non competitive GABA A receptor antagonist, baclofen, a GABA B receptor agonist, and delta-aminovaleric acid, a GABA B receptor antagonist, did not affect on the spontaneous and oxytocin induced contraction of the isolated rat uterus. The inhibitory actions of diazepam on the spontaneous and oxytocin induced contraction were not affected by all the GABA receptor agonists and antagonists, but exceptionally potentiated by bicuculline. This potentiation-effect by bicuculline was not antagonized by muscimol. In normal calcium PSS, addition of calcium restored the spontaneous contraction preinhibited by diazepam and recovered the contractile of oxytocin preinhibited by diazepam. A23187, a calcium inophore, enhanced the restoration of both the spontaneous and oxytocin induced contraction by addition of calcium. In calcium-free PSS, diazepam suppressed the restoration of spontaneous motility by addition of calcium but allowed the recovery of spontaneous motility to a considerable extent. Diazepam could not inhibit some development of contractility by oxytocin in calcium-free PSS, but inhibited the increase in contractility by subsequent addition of calcium. These results suggest that the inhibitory action of diazepam on the rat uterine motility does not depend on or related to GABA receptors and that diazepam inhibits the extracellular calcium influx to suppress the spontaneous and oxytocin induced contractilities.
The present studies were performed to investigate the interaction of $17{\beta}$-estradiol and human growth hormone(hGH) on the proliferation of human periodontal ligament(WDL) cell. The independent effects of $17{\beta}$ estradiol and hGH on hPDL cell proliferation were investigated and the effects of hGH on hPDL cell proliferation after $17{\beta}$-estradiol pre-treatment were also investigated. Lastly, the change of hGH receptor expression in hPDL cell after $17{\beta}$-estradiol pre-treatment were investigated. The obtained results were as follows; 1. The treatment of $17{\beta}$-estradiol or hGH had no significant effects on hPDL cell proliferation. 2. After pre-treatment of $17{\beta}$-estradiol, hGH stimulated the proliferation of the hPDL cell, regardless of hHG concentration. 3. Although there was not hGH receptor in the hPDL cell, hGH receptors were expressed in hPDL cell after more than 6 hours pre-treatment of $17{\beta}$-estradiol. 4. The effect of hGH on hPDL cell proliferation was related to the hGH receptor expression. $17{\beta}$-estradiol pre-treaaent contributed to the hGH effects on the hPDL cell by stimulating hGHR expression.
The uterus receives adrenergic terminals from the mesenteric ganglia and considerably large amount of catecholamines have been shown to be contained in this organ. On the other hand, the activities of epinephrine, norepinephrine or adrenergic nerve on uterine motility is so complicated that many controversial results have been reporter. Recently, a large number of reports concerning the changes of uterine catecholamines content have appeared, but little is known about the role of uterine catecholamines in their activities on uterine motility. The present experiments were undertaken to determine the significance of the intrinsic uterine catecholamines in the physiology of uterus. Female albino rabbits weighing approximately 2 kg were employed in this experiment. uterine strip3 were prepared and suspended in a constant temperature $bath(38^{\circ}C)$ containing 100 ml of Locke's solution aerated with 95% oxygen and 5% carbon dioxide. Spontaneous motility was recorded on a smoked drum with an isotonic lever. The catecholamines concentration of the uterus was determined according to the Procedure described of Shore and Olin (1958). Human uterus obtained from patients was also used to determine the catecholam ines content of myometrium. Followings are summarized results. 1) On the non-pregnant rabbit uterine strips, epinephrine and norepinephrine significantly elevated the tonus and stimulated the spontaneous motility. Pretreatment with dichloroisoproterenol(DCI), an adrenergic beta-receptor blocker, enhanced the stimulatory activity of epinephrine or norepinephrine. On the other hand, pretreatment with dibenamine, an adrenergic alpha-receptor blocker, rendered the uterine muscle to exhibit inhibition after the administration of epinephrine or norepinephrine. Following the treatment with both DCI and dibenamine, epinephrine or norepinephrine produced no appreciable effects on the spontaneous motility of the uterus. These results suggest there exist both alpha and beta-adrenergic receptors in the uterine muscle and the response to epinephrine of the former is predominant over that of latter in the non-pregnant uterus of rabbits. The total catecholamines concentration of the non-pregnant uterus was $351\;m{\mu}g/g$ and the fractional concentrations of epinephrine and norepinephrine were $125\;m{\mu}g/g(35.7%)$ and $226\;m{\mu}g/g$ respectively. It is interesting to note that the catecholamines content of uterus was characterized by a high fractional corcentration of epinephrine relative to norepinephrine. 2) On the pregnant rabbit uterine strips, the effects of epinephrine and norepinephrine varied according to the period of pregnancy. The response to epinephrine of adrenergic beta receptor of uterus increased during pregnancy, and the effect of catecholamine was inhibitory in the early pregnancy but became stimulatory as the pregnancy progressed. This stimulating action on the uterine motility was found to occur through the action of norepinephrine. The uterine catecholamines concentration was markedly reduced during pregnancy. The catecholamines concentration was started to decrease in the early pregnancy, reached the lowest level in the mid-pregnancy and then started to increaae again in the late pregnancy when the total catecholamines content became the highest level of all. This increase of catefholamines in late pregnancy was chiefly due to the increase of norepinephrine. These results suggest that the uterine motility may be related to the catecholamines content, especially norepinephrine content in the uterus. 3) Bilateral oophorectomy of rabbits results in a marked shrink of the uterus in size. The spontaneous motility of the uterine segment of these animals was very weak and irregular. Norepinephrine produced inhibitory effect, whereas epinephrine was stimulatory or inhibitory effect on the uterine segment. The total catecholamines tontent in whole uterus was markedly reduced. The injection of estrogen into the oophorectornized rabbit increased the weight of uterus to approximately three times of that of oophorectornized animal. The apontaneous motility and the response to epinephrine and norepinephrine of the uterine segment were greatly enhanced. Both epinephrine and norepinephrine produced a marked stimulatory effects of the uterine motility. The uterine content of catecholamines, particularly epinephrine, was markedly increased. The injection of progesterone into the oophorectornized rabbit increaeed the weight of uterus to approximately 2.5 times of that of eophorectornized animal. The spontaneous motility of the uterine segment was weak and irregular. Epinephrine produced stimulatory effect at high concentrations but norepinephrine always prcdnced inhibitory effect on the uterine segment. The uterine content of catecholamines, particularly of norepinephrine, was markedly reduced. These results suggested that ovarian hormones play an important role not only on the growth and spontaneous norepinephrine of uterus but also on the catecholamines content and responee to epinephrine and norepinephrine of the uterus. 4) The intraperitoneal injection of reserpine(3 mg/kg) into the non-pregnant, pregnant and oophorectornieed rabbits markedly decreased the uterine content of catecholamines, particularly of the norepinephrine. The stimulatory response to epinephrine and. norepinephrine of the uterine segment of these reserpinized ratbits was markedly reduced whereas the inhibitory response to these catecholamines was enhanced. This finding further support the close relationship between the uterine catecholamines content and uterine response to epineptrire and norepinephrine. 5) In the human uterus, the concentration of epinephrine was actrally greater than that of norepinephrine and it was significantly greater during the proliferative phase of the menstrtal cycle. In the human pregnant uterus, the concentrations of toth epinephrine and ncrefinephrine were markedly reduced and showed about 45 percent rednction after 6-8 weeks of ectopic Pregnancy. At full term ana during labor, the concentrations of epinephrine and norepinephrine at placental sites were less than those found in the non-pregnant group. Of interest was the finding that the norepinephrine concentration of uterus from toxemic patients was two and half times higher than that of lower uterine segment of the nontoxemic pregnant individuals. Also the epinephrine concentraticn was slightly increaeed.
Purpose: The purpose of this study was to determine if there were prognostic differences between BRCA related and BRCA non-related Korean patients with early-onset breast carcinomas. Materials and Methods: Sixty women who had developed breast cancers before the age of 40, and who were treated at the Soonchunhyang University Hospital, were studied independently of their family histories. The age range was 18 to 40 with a median of 34.5 years. Lymphocyte specimens from peripheral blood were studied for the heterozygous mutations of BRCA1 and BRCA2 using direct sequencing methods. Immunohistochemistry was peformed on the paraffin-embedded tissue blocks that were available. Results: Eleven deleterious mutations (18.3%, 6 in BRCA1 and 5 in BRCA2) and 7 missense mutations of unknown significance (11.7%), were found among the 60 patients. More than half of the mutation were novel, and were not reported in the database. Most of the BRCA-associated patients had no history of breast cancer. No treatment related failures were observed in the BRCA carriers, with the exception of one patient that had experienced a new primary tumor of the contralateral breast. The seven year relapse free survival rate were 50 and 79% In the BRCA carrier and BRCA negative patients, respectively. Although the expression of estrogen and progesterone receptors were less common, and histological features more aggressive, in the BRCA associated tumors, the outcome of the patients with BRCA mutations was not poorer than that on the patients without deleterious mutations. Conclusion.: Despite the BRCA mutation carriers having adverse prognostic features, the recurrence rate was relatively lower than that in the BRCA non-carrying Korean patients wi4h early-onset breast carcinomas. In addition, although the prevalence of the BRCA mutation in Korean patients was higher than that in white patients, the penetrance of the cancer seemed to be relatively low in Korean women carrying BRCA mutations. A large population based study of the BRCA mutation, with a long-term follow-up of the study patients will be required to confirm these results.
Purpose: To determine the patterns on evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was peformed. Materials and Methods: A web-based database system for korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998$\~$1999 from 15 hospitals were reviewed. Results: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9$\%$) followed by medullary carcinoma (4.2$\%$) and infiltrating lobular carcinoma (1.5$\%$). Pathologic T stage by AJCC was T1 in 59.7$\%$ of the casses, T2 in 29.5$\%$ of the cases, Tis in 8.8$\%$ of the cases. Axillary lymph node dissection was peformed I\in 91.2$\%$ of the cases and 69.7$\%$ were node negative. AJCC stage was 0 in 8.8$\%$ of the cases, stage I in 44.9$\%$ of the cases, stage IIa in 33.3$\%$ of the cases, and stage IIb in 8.4$\%$ of the cases. Estrogen and progesteron receptors were evaluated in 71.6$\%$, and 70.9$\%$ of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2$\%$, wide excision in 11.5$\%$, quadrantectomy in 23$\%$ and partial mastectomy in 27.5$\%$ of the cases. A pathologically confirmed negative margin was obtained in 90.8$\%$ of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90$\%$ of the planned radiotherapy dose. Radiotherapy volume was breast only In 88$\%$ of the cases, breast+supraclavicular fossa (SCL) in 5$\%$ of the cases, and breast+ SCL+ posterior axillary boost in 4.2%$\%$of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45$\~$59.4 Gy (median 50.4) and boost dose was 8$\~$20 Gy (median 10 Gy). The total radiation dose delivered was 50.4$\~$70.4 Gy (median 60.4 Gy). Conclusion: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.
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