eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation.

The eukaryotic translation initiation factor 3a (eIF3a) is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. Our previous study identified that it was correlated with platinum response in lung cancer. The current study aims to test the hypothesis that eIF3a may affect the drug response and prognosis of ovarian cancer patients receiving platinum-based chemotherapy by regulating xeroderma pigmentosum complementation group C (XPC) and p27(Kip1). Immunohistochemistry and western blot was used to determine the expression of eIF3a in 126 human ovarian cancer tissues followed by association analysis of eIF3a expression with patient's response and survival. Ectopic over-expression and RNA interference knockdown of eIF3a were carried out in A2780/cisplatin (DDP) and its parental A2780 cells, respectively, to determine the effect of altered eIF3a expression on cellular response to cisplatin by employing MTT assay. Western Blot analyses were also carried out to determine the regulation of eIF3a on XPC and p27(Kip1). eIF3a expression was associated with response of ovarian cancer patients to DDP-based chemotherapy and their survival. Overexpression and knockdown of eIF3a increased and decreased the cellular response to cisplatin in A2780/DDP and A2780 cells, respectively. In addition, XPC and p27(Kip1) were down regulated by eIF3a. eIF3a improves ovarian cancer patients' response to DDP-based chemotherapy via down regulating XPC and p27(Kip1).

[Opioid µ receptors mediate the stress-induced spatial reference memory impairment].

Learning/memory impairment is one of the most serious problems induced by stress, and the underlying mechanisms remain unclear. Opiates and opioid receptors are implicated in multiple physiological functions including learning and memory. However, there is no clear evidence whether the endogenous opioid system is involved in the formation of the stress-induced spatial reference memory impairment. The aim of the present study was to evaluate the role of µ opioid receptor in the stress-induced spatial reference memory impairment by means of Morris water maze (MWM) test in a mouse elevated platform stress model. The mice were trained in the MWM for four trials a session for 4 consecutive days after receiving the elevated platform stress, and intracerebroventricular injection of µ opioid receptor agonist DAMGO, antagonist CTAP or saline. Retention of the spatial training was assessed 24 h after the last training session with a 60-s free-swim probe trial using a new starting position. The results showed that intracerebroventricular injection of µ opioid receptor agonist DAMGO but not antagonist CTAP before MWM training impaired the memory retrieval of mice. Elevated platform stress before MWM training also impaired memory retrieval, which could be reversed by pre-injection of CTAP, and aggravated by DAMGO. These results suggest that endogenous opioid system may play a crucial role in the formation of the stress-induced memory impairment.

Quantitative proteomic study of human lung squamous carcinoma and normal bronchial epithelial acquired by laser capture microdissection.

OBJECTIVE: To investigate the differential protein profile of human lung squamous carcinoma (HLSC) and normal bronchial epithelium (NBE) and provide preliminary results for further study to explore the carcinogenic mechanism of HLSC. METHODS: Laser capture microdissection (LCM) was used to purify the target cells from 10 pairs of HLSC tissues and their matched NHBE, respectively. A stable-isotope labeled strategy using iTRAQ, followed by 2D-LC/Q-STAR mass spectrometry, was performed to separate and identify the differential expression proteins. RESULTS: A total of 96 differential expression proteins in the LCM-purified HLSC and NBE were identified. Compared with NBE, 49 proteins were upregulated and 47 proteins were downregulated in HLSC. Furthermore, the expression levels of the differential proteins including HSPB1, CKB, SCCA1, S100A8, as well as S100A9 were confirmed by western blot and tissue microarray and were consistent with the results of quantitative proteomics. CONCLUSION: The different expression proteins in HLSC will provide scientific foundation for further study to explore the carcinogenic mechanism of HLSC.

[Expression of EVEC in ovarian carcinoma and its biological significance].

OBJECTIVE: To investigate the expression of EVEC in ovarian carcinoma and explore its biological significance. METHODS: The expression of EVEC in 22 specimens of normal ovarian tissues and 63 specimens of ovarian cancers was detected by RT-PCR and Western blotting analysis, respectively. RESULTS: RT-PCR showed that the expression level of EVEC in stage I-II ovarian cancer (0.199 ± 0.014) was significantly higher than that in stage III-IV ovarian cancer (0.155 ± 0.015, P < 0.05), and significantly lower than that in normal ovarian tissues (0.415 ± 0.055, P < 0.05). There was no significant difference between the expression levels of EVEC in primary sites and that in corresponding metastatic sites of ovarian cancer (P > 0.05). Furthermore, the results of Western blot also showed that the protein expression level of EVEC in stage I-II ovarian cancer was also significantly lower than that in normal ovarian tissues (0.179 ± 0.026 vs. 0.543 ± 0.032, P < 0.05), and higher than that in stage III-IV ovarian cancer (0.179 ± 0.026 vs. 0.115 ± 0.023, P < 0.05). The EVEC expression level in the epiploic metastasis of stage I-II ovarian cancer was significantly higher than that of stage III-IV ovarian cancer (0.201 ± 0.028 vs. 0.101 ± 0.037, P < 0.05). The expression of EVEC in ovarian carcinoma had no correlation with age, pathologic classification and histological grade (P > 0.05). CONCLUSIONS: EVEC is closely related with carcinoma metastasis. The expression of EVEC in ovarian cancer and its metastatic sites was remarkably decreased. EVEC may play a negative role in the development and metastasis of ovarian cancer and may be a valuable marker in estimation of the prognosis for patients.

[Proteomic study of paclitaxel on human cervical carcinoma HCE1].

OBJECTIVE: To explore the mechanism of paclitaxel on the protein expression of human cervical carcinoma cell line HCE1. METHODS: The total proteins extracted from paclitaxel-treated HCE1 cells were analyzed by 2-dimensional gel electrophoresis (2-DE), and compared with those from untreated HCE1 cells. The differential proteins were identified by mass spectrometry. Western blot was used to determine the differential expression levels of the 2 proteins. RESULTS: At 24 hour after paclitaxel (0.05 mumol/L) treatment, 2-DE images of paclitaxel-treated and paclitaxel-untreated cells were analyzed. Forty-two differential proteins were found. Twenty-one differential proteins among 42 proteins were analyzed by mass spectrometry, among which 15 proteins were identified, including peptidyl-prolylisomerases A (PPIase A),alpha-enolase,keratin 8,heat shock protein 90, eukaryotic translation initiation factor 1A, and so on. CONCLUSION: Fifteen proteins in human cervical carcinoma cells paclitaxel-treated and paclitaxel-untreated are found by proteomic techniques. These proteins may be involved in the proliferation inhibition of human cervical carcinoma cells by paclitaxel.

[Surgical pattern of radical hysterectomy and pelvic lymph node dissection for patients with cervical cancer].

OBJECTIVE: To investigate the probability of improving radical surgery to resect uterus thoroughly and to decrease various complications after the surgery. METHODS: We compared the clinical effect of reformed radical hysterectomy for 79 patients with the effect of tradition radical hysterectomy for 60 patients. Reformed surgery had the following features: We firstly resected the uterus and then dissected the pelvic lymph node. Urinary bladder gap and rectum gap were opened. After exposing the route of ureter, we excised the uterus artery at the point between the ureter and the uterus artery. Cardinal ligament and uterosacral ligament were cut off by electric knives. The pelvic lymph node was dissected with a titanium pinch. RESULTS: The average operation time and the time of keeping uterine pipe were shortened. Bleeding during the operation was reduced. No complication was observed. All patients were followed up for 11 to 20 months and no patient died. One patient recurred. CONCLUSION: Reformed surgery can resect the uterus, dissect the pelvic lymph node thoroughly, and reduce various complications. The reformed surgery can not only ensure the curative effect, but also benefit patient's recovery and life quality.

[Clinical analysis of 9 cases of the normal-sized ovary carcinoma syndrome].

OBJECTIVE: To investigate clinical features, diagnostic criteria, treatment methods of a clinically rare "normal-sized ovary carcinoma syndrome". METHODS: Histologic slices of 9 cases of the normal-sized ovary carcinoma syndrome from 1990 to 1996 were retrospectively reviewed. Six of the 9 cases were extraovarian peritoneal serous papillary carcinoma(EPSPC). The other 3 cases were serous adenocarcinoma of the ovary (2 cases) and metastatic adenocarcinoma of unknown origin (1 case). All the patients received optimal cytoreductive surgery combined with multiple courses of effective adjuvant chemotherapy. RESULTS: Two patients with EPSPC survived for 84 months and 72 months respectively up to Dec., 1997. The average survival time of the 7 patients who died of their diseases was 16.5 months. CONCLUSION: For the normal-sized ovary carcinoma syndrome, surgical resection is the first choice of treatment, and postoperative chemotherapy is essential to obtain better prognosis.