Primary ectopic substernal thyroid cancer with trachea relapse: a case report and opinions of management.

BACKGROUND: Ectopic substernal thyroid is a rare symptom of thyroid disease that entirely results from the developmental defects at early stages of thyroid embryogenesis and during its descent. Cases were seldom reported as primary ectopic substernal thyroid cancer, especially those with severe local invasion and tracheal relapse. CASE PRESENTATION: In this report, the patient presented odynophagia and a sense of progressing swallowing obstruction. She underwent total thyroidectomy and lump resection. However, she refused to use postoperative radioactive iodine or take adjuvant external-beam radiotherapy, except for thyroid hormone replacement therapy. Tracheal relapse was observed after 6 months. Tracheal stent was used to reconstruct the airway twice. CONCLUSIONS: Trachea invasion might be a worse independent predictor of prognosis than any others and should be given particular attention. Furthermore, tracheal stent might be a palliative option for patients with tracheal relapse.

[Clinical significance of CC3/TIP30 expression in breast carcinoma and its correlation with HER-2/neu].

OBJECTIVE: To explore the clinical significance of CC3/TIP30 protein's expression in breast carcinoma and its correlation with HER-2/neu. METHODS: The expression of CC3/TIP30 and HER-2/neu protein was detected in 112 breast cancer tissues which was collected from January 2004 to January 2005 by immunohistochemistry and the relationship with clinic pathological parameters and prognosis was analyzed. Small interfering RNA (siRNA) which target to knock out CC3/TIP30 were transfected into SK-BR-3 cells. Real-time PCR were used to detect the level of CC3/TIP30 and HER-2/neu mRNA. RESULTS: The results of immunohistochemistry showed CC3/TIP30 protein was correlated with TNM stage, lymph node status, HER-2 status and molecule classification (P = 0.048, 0.019, 0.027, 0.011), but there was no association with age, tumor size, estrogen receptor and progesterone receptor. Real-time PCR results revealed that CC3/TIP30 siRNA down-regulation the level of its mRNA, accompanied by a decline in the expression of HER-2/neu gene mRNA, the difference was statistically significant (F = 56.797, P = 0.000; F = 165.101, P = 0.000). In addition, Kaplan-Meier curves of disease-specific survival analysis showed a marked difference in the subtype of HER-2 protein positive between CC3/TIP30 positive group and negative group (χ(2) = 10.732, P = 0.001). CONCLUSIONS: The loss of CC3/TIP30 is related to occurrence and development in breast cancer, suggesting early onset of metastasis and recurrence. Perhaps CC3/TIP30 can be considered as a sub-typing indicator in HER-2 positive breast cancer.

circGFRA1 affects the sensitivity of triple-negative breast cancer cells to paclitaxel via the miR-361-5p/TLR4 pathway.

In recent years, the role of circular RNAs (circRNAs) in tumours has attracted widespread attention. Some circRNAs have been reported to play a role in triple-negative breast cancer (TNBC). However, circRNAs have rarely been reported in terms of TNBC resistance. This study aimed to clarify that circGFRA1 affects the sensitivity of TNBC cells to paclitaxel (PTX) by the miR-361-5p/TLR4 pathway. Compared with the non-PTX-resistant TNBC cell line MDA-MB-231, the expression of circGFRA1 in the PTX-resistant TNBC cell line MDA-MB-231.PR was significantly increased. The small hairpin RNA-mediated circGFRA1 knockdown inhibited the resistance of TNBC cells to PTX. RNA pull-down assay and luciferase reporter gene assay confirmed the binding between circGFRA1 and miR-361-5p and between miR-361-5p and TLR4. It has been proven that circGFRA1 knockdown can inhibit the resistance of TNBC cells to PTX by promoting the expression of miR-361-5p, and subsequently reduce the expression of TLR4.

[Efficacy and safety of remifemin compared to tibolone for controlling of perimenopausal symptoms].

OBJECTIVE: To investigate the efficacy and safety of remifemin (isopropanolic extract of cimicifuga racemosa) treating perimenopausal symptoms in comparison of tibolone. METHODS: One hundred and eighty postmenopausal women at range of 40 - 60 years old were enrolled in a multicenter, randomized and double blind study. They were divided into remifemin and tibolone group at ratio 1:1. The therapeutic strategy was remifemin 20 mg bid po for 12 weeks in remifemin group and tibolone 2.5 mg qd po for 12 weeks in tibolone group. To evaluate therapeutic effect, total score of Kupperman menopause index (KMI) was used as the major observed index and single item score of KMI were secondary observed index. Safety warning was determined by laboratory tests and adverse events at timepoint of before, at 4 and 12 weeks treatment. RESULTS: (1) Total score of KMI: it were 24 +/- 5 in remifemin group and 25 +/- 6 in tibolone group before treatment. At timepoint of 4 weeks treatment, it were 11 +/- 6 in remifemin group and 11 +/- 7 in tibolone group. At timepoint of 12 weeks treatment, it were 7 +/- 6 in remifemin group and 6 +/- 5 in tibolone group. Total KMI score between two groups did not show statistical difference at various timepoint (P > 0.05). (2) Single item score of KMI: when compared before, at 4 and 12 weeks treatment, did show remarkable difference (P < 0.05) either in remifemin or in tibolone group. However, those single items of KMI score did not show statistical difference between 4 and 12 weeks timepoint in each treatment group (P > 0.05). (3) Adverse effect: the incidence of adverse effect in remifemin group was significantly lower than that of tibolone group. None case with vaginal bleeding was observed in remifemin group, however, 17 cases with vaginal bleeding occurred in tibolone group (19%, 17/90). The incidence of breast swelling were 16% (14/90) in remifemin group and 36% (32/90) in tibolone group; before treatment, the thickness of endometrium were (2.6 +/- 1.1) mm in remifemin group and (2.8 +/- 1.1) mm in tibolone group; at timepoint of 12 weeks treatment, the thickness of endometrium were (2.9 +/- 1.4) mm in remifemin group and (3.4 +/- 2.0) mm in tibolone group. In comparison of thickness of endometrium before and at 12 weeks treatment, no remarkable changes was observed in remifemin group, however, endometrium displayed significantly thicker in tibolone group. CONCLUSIONS: Our study suggested that remifemin was one effective and safe agent to manage women with climacteric symptom. It has similar therapeutic effect and lower incidence of adverse effect when compared with tibolone.

[Clinical trial on the effectiveness and safety of triptorelin in treatment of uterine leiomyoma].

OBJECTIVE: To evaluate the effectiveness and safety of triptorelin in the treatment of uterine leiomyoma. METHODS: A multi-center, prospective, randomly controlled clinical trial was carried out from Dec. 2002 to Mar. 2004 in three university hospitals. A total of 125 qualified patients with uterine leiomyoma were randomly divided into either triptorelin group (63 cases) treated with 3.75 mg triptorelin injected intramuscularly or leuprorelin group (62 cases) treated with 3.75 mg leuprorelin injected subcutaneously. Both drugs were injected every 28 days for a total of 3 months. RESULTS: All 125 patients finished the trial. The uterine volumes were similar before treatment between the triptorelin group and the leuprorelin group and were decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 51% and 49%, respectively, without significant difference between two groups (P > 0.05). The volumes of the largest leiomyoma decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 50% and 48% in the triptorelin and leuprorelin groups, respectively, without significant difference between them (P > 0.05). Patients with serum level of 17beta-estradiol < 183 pmol/L accounted for 94% in both groups. The hemoglobin and serum ferrum levels were both significantly increased in the two groups after treatment (P < 0.05). The amenorrhea rates after 3 months of treatment were 97% in the triptorelin group and 95% in the leuprorelin group (P > 0.05). Dysmenorrhea, noncyclic pelvic pain and pressure-like symptoms were relieved quickly and remarkably in both groups after treatment. The rates of adverse event occurred in 71% of patients in both groups. The main side effects included flare-up effects and hypoestrogenic symptoms. Nine patients in the triptorelin group and 6 in the leuprorelin group received add-back therapy with tibolone 1.25-2.50 mg/d because of remarkable climacteric-like symptoms. CONCLUSION: Treatment of uterine leiomyoma with triptorelin for 3 months is both effective and safe in Chinese women.

[Study on the relationship between some genetic factors and peak bone mineral density in Beijing young women].

OBJECTIVE: To evaluate the relationship between the peak bone mineral density (PBMD) and vitamin D receptor (VDR), estrogen receptor (ER) allelic variants in Beijing young women. METHODS: From March, 2000 to July, 2001, one hundred and fifty-nine young healthy women (25 - 37 years old) in Beijing were voluntarily enrolled in the study. (1) BMD were measured by dual energy X-ray absorptiometry (DXEA) at lumbar and hip. (2) The polymorphism of VDR and ER genes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). (3) The relationship between BMD and polymorphism of VDR and ER genes were examined. RESULTS: (1) Lumber BMD was positively correlated to height, weight and body mass index (BMI), whereas, the femoral neck BMD only to weight, and the other sites of hip BMD to BMI. (2) Although subjects with the VDR bb genotype had higher BMD than those with Bb genotype at lumber, femoral neck, inter and troch, no significant difference was found (P > 0.05). (3) In Ward triangle, subjects with ER PP genotype had significantly lower BMD than those in ER Pp and pp genotypes (P < 0.05). (4) Women with BbPP genotype combination had lower BMD levels at lumber and hip, and with bbPP and Bbpp genotypes combination significantly higher lumber BMD levels than BbPP genotype (P < 0.05). However, the differences of BMD among subjects with different VDR and ER genotypes became not significant after adjusting the confounder of body weight. CONCLUSIONS: (1) Body weight and BMI play important roles to PBMD of Beijing women. (2) There was no significant difference of BMD levels between VDR genotypes at any site. (3) PvuII polymorphism of ER gene was associated with low Ward triangle BMD. (4) There was significant relationship between the combination of ER and VDR polymorphisms at lumbar and hip BMD. Our data suggest that genetic variation at the ER locus, singly and in relation to the VDR locus, may influence the attainment and maintenance of peak bone mass in young women.

[A randomised clinical trial to study the effects of raloxifene hydrochloride on bone mineral density, biochemical markers of bone metabolism and serum lipids in postmenopausal women].

OBJECTIVE: To determine the effect of raloxifene hydrochloride (RLX) on bone mineral density (BMD), biochemical markers of bone metabolism and lipid metabolism in Chinese postmenopausal women. METHODS: This was a multicenter, randomized, double blind placebo controlled study in China with a total of 204 postmenopausal women [mean age (60 +/- 5) years (x +/- s) and weight (63 +/- 9) kg (x +/- s)] treated with either RLX 60 mg (n = 102) or placebo (n = 102) daily for 12 months. BMD, serum lipid and bone markers were determined before and after drug administration. RESULTS: Compared to placebo, RLX produced a significant increase in both total lumbar spine and total hip BMD. For the lumbar spine, percentage increase in total BMD was 2.30% with RLX compared to a decrease of 0.08% with placebo (P < 0.001). Corresponding values for total hip BMD were 2.46% increase for RLX and 1.07% for placebo (P < 0.05). For biochemical markers of bone metabolism, serum osteocalcin and C-telopeptide, percentage decrease were 27.6% and 24.0% in raloxifene-treated subjects. Corresponding values in placebo were 10.6% decrease and 15.8% increase (RLX compared to placebo, both P < 0.001). For total cholesterol and low-density lipoprotein cholesterol, percentage decrease were 6.4% and 34.6% in the raloxifene-treated group. Corresponding values in placebo were 1.4% increase and 19.1% decrease (RLX compared to placebo, both P < 0.001). No differences were found for high-density lipoprotein cholesterol or triglyceride levels between the two groups. Only 5 subjects discontinued early due to an adverse event (3 in the RLX group and 2 in the placebo group). CONCLUSIONS: This study confirms that RLX exerts positive effects on the skeleton, increasing BMD and decreasing biochemical markers of bone metabolism, and decreased total cholesterol and low-density lipoprotein cholesterol in postmenopausal women in China.

Effects of miR-155 antisense oligonucleotide on breast carcinoma cell line MDA-MB-157 and implanted tumors.

Diverse studies have shown that miR-155 is overexpressed in different tumor types. However, the precise molecular mechanism of the ectopic expression of miR-155 in breast cancer is still poorly understood. To further explore the role of miR-155 in breast tumorigenesis, we here assessed the influence of miR-155 antisense oligonucleotide (miR-155 ASO) on MDA-MB-157 cell viability and apoptosis in vitro. Furthermore, the effects of inhibitory effects of miR-155 on the growth of xenograft tumors in vivo were determined with performance of immunohistochemistry to detect expression of caspase-3, a pivotal apoptosis regulatory factor, in xenografts. Transfection efficiency detected by laser confocal microscope was higher than 80%. The level of miR-155 expression was significantly decreased (P<0.05) in the cells transfected with miR-155 ASO, compared with that in cells transfected with a negative control. After being transfected with miR-155 ASO, the viability of MDA-MB-157 cells was reduced greatly (P<0.05) and the number of apoptotic cells was increased significantly. Additionally, miR-155 ASO inhibited the growth of transplanted tumor in vivo and significantly increased the expression of caspase-3. Taken together, our study revealed that miR-155 ASO can induce cell apoptosis and inhibit cell proliferation in vitro. Moreover, miR-155 ASO could significantly repress tumor growth in vivo, presumably by inducing apoptosis via caspase-3 up-regulation. These findings provide experimental evidence for using miR-155 as a therapeutic target of breast carcinoma.

Clinical significance of miR-155 expression in breast cancer and effects of miR-155 ASO on cell viability and apoptosis.

Accumulating evidence shows that mircroRNAs (miRNAs) play a vital role in tumorigenesis. miR-155 is one of the most multifunctional miRNAs whose overexpression has been found to be associated with different types of cancer including breast cancer. To further determine the potential involvement of miR-155 in breast cancer, we evaluated the expression levels of miR-155 by real-time PCR and correlated the results with clinicopathological features. Matched non-tumor and tumor tissues of 42 infiltrating ductal carcinomas and 3 infiltrating lobular carcinomas were analyzed for miR-155 expression by real-time PCR. Further, we used an antisense technique to inhibit miR-155 expression in vitro. WST-8 test was performed to evaluate cell viability and apoptosis assay was used to investigate the effect of the miR-155 antisense oligonucleotide (miR-155 ASO) on HS578T cell death. The expression levels of miR-155 were significantly higher in tumor tissues than the levels in matched non-tumor tissues (P<0.001). Up-regulated miR-155 expression was associated with lymph node positivity (P=0.034), higher proliferation index (Ki-67 >10%) (P=0.019) and advanced breast cancer TNM clinical stage (P=0.002). Interestingly, we next found that miR-155 expression levels had close relations with ER status (P=0.041) and PR status (P=0.029). Transfection efficiency detected by flow cytometry was higher than 70%, the WST-8 test showed that viability of HS578T cells was greatly reduced after transfection with miR-155 ASO compared with the scramble (SCR) group or the liposome group. The Annexin V-FITC/PI assay also indicated that transfection with miR-155 ASO promoted apoptosis.