光照周期对文昌鱼生殖细胞发生和性腺生长的影响

厦门文昌鱼性腺发育,因季节和生态因子的不同,呈明显的年周期变化(方永强等,1989)。然而,光照周期对文昌鱼性腺发育有何影响,迄今仍缺乏了解(Guraya,1983)。为此,本文分三组不同光照周期的实验,结果发现光照可影响文昌鱼生殖细胞发生和性腺生长。 文昌鱼(Branchiostoma belcheri Gray)取自厦门琼头海区。本实验在1987年12月至1988年2月,分三组不同光照周期:第一组 8L(light)—16D(dark)(光照 8小时,黑暗16小时),第二组12L—

性激素与促性腺激素对卵巢癌SKOV3细胞体外生长调控及其机制的研究

目的性激素和促性腺激素对卵巢癌的影响一直存在争议,文中研究性激素和促性腺激素对卵巢癌细胞株的体外生长的调控,并探讨可能机制,为进一步的临床研究提供理论依据。方法将不同浓度雌激素、孕激素、人绒毛促性腺生长激素(human chorionic gonadotropin,hCG)作用于卵巢癌细胞株SKOV3,利用四甲基偶氮唑兰(MTT)比色法检测细胞在24、48、72h的增殖情况,流式细胞仪检测用药后细胞凋亡率及细胞周期的改变,实时荧光定量PCR检测用药前后各组细胞表皮生长因子受体(epidermal growth factor receptor,EGFR)、Bcl-2、Bax mRNA的表达量。结果孕激素和浓度为10-4mol/L的雌激素抑制细胞的生长,诱导细胞凋亡,作用细胞72h其EGFR、Bcl-2 mRNA表达量显著下调;10-4mol/L的雌激素作用72 h后细胞周期分布以S期为主,孕激素作用72 h后大量细胞阻滞在G0/G1期;hCG和浓度小于10-6mol/L的雌激素促进细胞增殖,作用细胞72 h其EGFR、Bcl-2 mRNA表达量均上调显著,细胞周期分布G2/M期增多。结论孕激素和高浓度的雌激素能抑制卵巢癌细胞的增殖,其机制可能是通过将细胞分别阻滞于G0/G1、S期,下调EGFR和Bcl-2的表达而诱导细胞凋亡来实现的。HCG和低浓度的雌激素能刺激卵巢癌细胞的增殖,其机制可能是通过上调EGFR和Bcl-2的表达而抑制细胞凋亡来实现的。

脑非妊娠性绒毛膜上皮癌的诊断和治疗(附2例报告)

目的探讨非妊娠性绒毛膜上皮癌的相关临床问题。方法分析2例不同来源的男性绒癌患者的临床和手术后随访资料。结果2例患者均在术后经病理确诊为绒癌,查血β-HCG均有不同程度升高。1例病情迅速恶化死亡;1例在术后接受了进一步放疗,随访半年情况良好。结论非妊娠性绒癌是少见的高度恶性肿瘤,常急性起病,临床表现多变,术前诊断较为困难,HCG对疾病的诊断和观察有重要作用。

成年男性原发于隐睾生殖细胞肿瘤临床病理观察

目的探讨男性原发于隐睾生殖细胞肿瘤的临床病理特征及免疫表型。方法对1例成年男性原发于隐睾生殖细胞肿瘤进行组织病理学观察及免疫组化检测,复习临床资料和相关文献。结果本例临床主要症状为反复腹痛,查血HCG异常升高,影像学显示盆腔巨大占位。病理穿刺诊断为生殖细胞肿瘤,主要成分为绒癌。镜下见丰富的合体滋养型癌细胞和单核滋养型癌细胞。免疫组化:HCG、CK7、CK20、Ki-67和p53(+),CK14、D2-40、MC、calretinin、TTF-1、CD30、PLAP、ER、PR、AFP和hepatocyte(-)。结论成年男性原发于隐睾以绒癌为主的生殖细胞肿瘤一般很难及时发现,误诊率极高,且绒癌恶性程度高,预后差。

Fractalkine and TGF-β1 levels reflect the severity of chronic pancreatitis in humans

MM： To clarify whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of chronic pancreatitis （CP）. This study aimed at clarifying whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of CR METHODS： Serum monocyte chemoattractant protein-1 （MCP-1）, transforming growth factor beta-1 （TGF-βI）, and soluble type fractalkine （s-fractalkine） concentrations were examined in patients with CP （n = 109） and healthy controls （n = 116）. Severity of disease was classified in patients with CP by a staging system. Relationships between stage-specific various clinical factors and serum MCP-1, TGF-β1, and s-fractalkine levels were investigated. Furthermore, 57 patients with non-alcoholic CP were similarly evaluated in order to exclude influence of alcohol intake. RESULTS： Patients with CP showed significant higher levels of serum TGF-β1 and s-fractalkine, but not MCP-1, compared to the controls. Serum TGF-β1 in the severe stage and s-fractalkine in the mild and thesevere stage of CP significantly increased compared to those of controls. However, it was observed that both TGF-β1 and s-fractalkine levels were affected by alcohol intake. In patients with non-alcoholic CP, serum TGF-β1 showed significant increase in the moderate stage of CP, and serum s-fractalkine revealed significant increase in the early stage of CP. CONCLUSION： It is suggested that the measurement of serum F-fractalkine is useful to diagnose early- stage CP. Moreover, the combined determination of both, s-fractalkine and TGF-β1, in human sera may be helpful in evaluating the severity status of CP.

EPIDERMAL GROWTH FACTOR PREVENTS INCREASED PERMEABILITY AND BACTERIAL TRANSLOCATION IN RATS WITH ACUTE PANCREATITIS

To evaluate the effects of epidermal growth factor (EGF) on intestinal permeability and bacterial translocation in rats with acute pancreatitis during total parenteral nutrition (TPN). Methods. Thirty- two male Sprague- Dawley rats that underwent injection of 3.5％ sodium taurocholate solution into the pancreatic duct were randomly divided into one of the following two groups: (1) received only TPN (control group) or (2) received TPN with EGF at a dose of 0.2 mg· kg- 1· day- 1 (Egf group). On fifth day of total parenteral nutrition, samples from mesenteric lymph nodes, pancreas, liver and spleen were harvested for cultures. Water, protein and DNA content in jejunal mucosa were determined. D- xylose and fluorescein isothiocyanate (FITC)- dextran were instilled into the lumen of a ligated segament of small intestine. Thirty minutes later, superior mesenteric vein D- xylose and plasma FITC- dextran concentration were measured. Results. Positive cultures in liver and spleen, as well as FITC- dextran concentration in the Egf group were significantly lower than in the control group. Protein and DNA content in jejunal mucosa in the Egf group were significantly higher than in the control group. Conclusion. The results indicate that EGF may prevent increased intestinal permeability and bacterial translocation in rats with acute pancreatitis during TPN.

Inhibitory effects of antisense phosphorothioate oligodeoxynucleotides on pancreatic cancer cell Bxpc-3 telomerase activity and cell growth in vitro

AIM： To investigate the effect of telomerase hTERT gene antisense oligonucleotide （hTERT-ASO） on proliferation and telomerase activity of pancreatic cancer cell line Bxpc-3. METHODS： MTT assay was used to detect the effect of different doses of hTERT-ASO on proliferation of Bxpc-3 cell for different times. To study the anti-tumor activity, the cells were divided into there groups： Control group （pancreatic cancer cell Bxpc-3）; antisense oligonucleotide （hTERT-ASO） group; and nosense oligonucleotide group decorated with phosphorothioate. Telomerase activity was detected using TRAP-PCR-ELISA. Cell DNA distribution was examined using flow cytometry assay. Cell apoptosis was observed by transmission electron microscope in each group. RESULTS： After treatment with 6 mmollL hTERT- ASO, cell proliferation was inhibited in dose- and time- dependent manner. The telomerase activity decreased after treatment with hTERT-ASO for 72 h. Flow cytometry showed the cell number of G0/G1 phase increased from 2.7% to 14.7%, the cell number of S phase decreased from 72.7% to 51.0%, and a sub-G1 stage cell apoptosis peak appeared in front of G1 stage. CONCLUSION： Telomerase antisense oligodeoxy- nucleotide can inhibit the proliferation of pancreatic cancer cell line Bxpc-3 and decrease the telomerase activity and increase cell apoptosis rate in vitro.

Dickkopf3 overexpression inhibits pancreatic cancer cell growth in vitro

AIM:To elucidate the role of dickkopf3(Dkk3)in human pancreatic cancer cell growth.METHODS:Dkk3 mRNA and protein expression in human pancreatic cancer cell lines were detected by realtime reverse transcription polymerase chain reaction(realtime RTPCR),Western blotting and immunofluorescence.Methylation of the Dkk3 promoter sequence was examined by methylationspecific polymerase chain reaction(MSP)and Dkk3 mRNA expression was determined by realtime RTPCR after 5aza2'deoxycytidine(5azadC)treatment.The effects of Dkk3 on cancer cell proliferation and in vitro sensitivity to gemcitabine were investigated by CellTiter 96?AQueous One Solution Cell Proliferation Assay(MTS)after transfecting the Dkk3 expression plasmid into human pancreatic cancer cells.The expression ofβcatenin,phosphorylated extracellular signalregulated protein kinases(pERK)and extracellular signalregulated protein kinases(ERK)was also examined by realtime RTPCR and Western blotting after upregulating Dkk3 expression in human pancreatic cancer cells.RESULTS:The results show that the expression levels of both Dkk3 mRNA and protein were low in all pancreatic cancer cell lines tested.The Dkk3 promoter sequence was methylated in the MIA PaCa2 and AsPC1 cell lines,which showed reduced Dkk3 expression.These two cell lines,which initially had a methylated Dkk3 promoter,showed increased Dkk3 mRNA expression that was dependent upon the dosage and timing of the DNA demethylating agent,5azadC,treatment(P<0.05 or P<0.01).When Dkk3 expression was upregulated following the transfection of a Dkk3 expression plasmid into MIA PaCa2 cells,the ability of cells to proliferate decreased(P<0.01),and the expression ofβcatenin and pERK was downregulated(P<0.01).Sensitivity to gemcitabine was enhanced in Dkk3 expression plasmidtransfected cells.CONCLUSION:Our findings,for the first time,implicate Dkk3 as a tumor suppressor in human pancreatic cancer,through the downregulation ofβcatenin expression via the ERKmediated pathway.

Triple negative breast cancer: 5 years follow-up

Objective： The aim of the study was to investigate the long-term therapeutic effects of triple negative breast cancers （TNBCs） and find a standardized treatment. Methods： The clinical data and survival status of 69 patients with TNBC were collected, who were treated from 2003 to 2007 at Chongqing Cancer Institute, China. Results： Median observation for 61 months showed the local recurrence rate was 13.0% （9/69）, the overall survival （OS） rate was 76.8% （53/69） and the disease free survival （DFS） rate was 59.4% （41169）. Log-rank univariate survival analysis showed the OS and DFS rates of TNBCs with axillary lymph node metastasis were 38.1% and 23.8%, respectively, and the OS and DFS rates of triple negative breast cancer with axillary lymph node non-metastasis were 93.6% and 75.0%, respectively. There were significant differences comparing with two groups. Indictor analysis of age, menstruation status, tumor size, TNM stage, histological type, neoadjuvant chemotherapy and p53 did not show any prognostic influence. Conclusion： The axillary nodes metastasis is associated with DFS and OS in triple negative breast cancers. Cisplatin-based chemotherapy may be good choice for triple negative breast cancers with metastasis or local recurrence, who received Anthracycline and Taxane-based chemotherapy. Targeted therapies strategies such as EGFR-targeted therapy may be necessary.

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.

Cardiac toxicity of trastuzumab in elderly patients with breast cancer

Breast cancer （BC） is diagnosed in 〉 65 year old women in about half of cases. Experts currently recommend that systemic therapy is offered to elderly patients with BC, if, based on their overall conditions and life expectancy, it can be reasonably anticipated that the benefits will outweigh the risks of treatment. Like for young subjects, the monoclonal antibody against human epidermal growth factor receptor-2 （HER-2）, trastuzumab, represents a valid therapeutic option when BC over-expresses this receptor. Unforttmately, administration of trastu- zumab is associated with the occurrence of left ventricular dysfunction and chronic heart failure （CHF）, possibly because of interference with the homeostatic functions of HER-2 in the heart. Registry-based, retrospective analyses have reported an incidence of CHF around 25% in elderly women receiving trastuzumab compared with 10%-15% in those not given any therapy for BC, and the risk of CHF has been estimated to be two-fold higher in 〉 60455 year old trastuzumab users vs. non-users. Extremely advanced age and preexisting cardiac disease have been shown to predispose to trastuzumab cardiotoxicity. Therefore, selection of older patients for treatment with trastuzumab should be primarily based on their general status and the presence of comorbidities; previous chemotherapy, especially with anthracyclines, should be also taken into account. Once therapy has started, efforts should be made to ensure regular cardiac surveillance. The role of selected biomarkers, such as cardiac troponin, or new imaging techniques （three-dimension, tissue Doppler echocardiography, magnetic resonance imaging） is promising, but must be further investigated especially in the elderly. Moreover, additional studies are needed in order to better understand the mechanisms by which trastuzumab affects the old heart.

EFFECT OF SOMATOSTATIN ON THE EXPRESSION OF TNF α mRNA IN MULTIORGANS OF RATS WITH ACUTE HEMORRHAGIC NECROTIC PANCREATITIS

Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT－PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.

Intestinal-type sinonasal adenocarcinoma with bone metastasis: a case report

Intestinal type adenocarcinoma is a slow growing tumor of sinonasal area, that account for 4% of malignancies of this area. In women it occurs sporadically. This tumor rarely metastasis to other organs. In this article we presented a woman with sinonasal intestinal type adenocarcinoma with optic nerve involvement and multiple bone metastasis.

Targeting key signalling pathways in oesophageal adenocarcinoma:A reality for personalised medicine?

Cancer treatments are rapidly changing.Curative treatment for oesophageal adenocarcinoma currently involves surgery and cytotoxic chemotherapy or chemoradiotherapy.Outcomes for both regimes are generally poor as a result of tumor recurrence.We have reviewed the key signalling pathways associated with oesophageal adenocarcinomas and discussed the recent trials of novel agents that attempt to target these pathways.There are many trials underway with the aim of improving survival in oesophageal cancer.Currently,phase 2 and 3 trials are focused on MAP kinase inhibition,either through inhibition of growth factor receptors or signal transducer proteins.In order to avoid tumor resistance,it appears to be clear that targeted therapy will be needed to combat the multiple signalling pathways that are in operation in oesophageal adenocarcinomas.This may be achievable in the future with the advent of gene signatures and a combinatorial approach.

Comparative Study of the Growth and Gonad Development of Clarias gariepinus （Burchell 1822） Fed Diets with Plant and Animal-based Ingredients in Concrete Tanks

A twelve week experiment was conducted to compare the effects of diets with plant-based and animal-based ingredients on growth and gonad development of Clarias gariepinus. One hundred and 12 sub-adult C. gariepinus with an average weight of 205 ×5.09 g, were stocked in six concrete tanks （9 × 4 × 2 m3） containing 20 fish each. Experiment had 3 replicates and animals fed daily at 5% body weights. There was no significant difference （P 〈 0.05） in proximate compositions of the two experimental feeds and controls. Fecundity, gonad weight and gonasomatic index were higher in fish fed diet 13 than A and C. Similarly, growth indices were higher in fish fed diet B than in A and C. Histology of gonads showed a faster development of oocytes of eggs in fish fed animal-based ingredients than plant-based and combined plant and animal diets. Although there were slight differences in growth parameters and gonad development in favor of feed with animal-based ingredients, plant-based feed compared favorably in the growth and gonad development of C. gariepinus. Plant-based ingredients are recommended on the basis of affordability and availability as substitute for animal-based ingredients in C. gariepinus feed.

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Objective： To construct a recombinant adenovirus vector-carrying human growth and differentiation factor-5 （GDF-5） gene, investigate the biological effects of adenovirus-mediated GDF-5 （Ad-GDF-5） on extracellular matrix （ECM） expression in human degenerative disc nucleus pulposus （NP） cells, and explore a candidate gene therapy method for intervertebral disc degeneration （IDD）. Methods： Human NP cells of a degenerative disc were isolated, cultured, and infected with Ad-GDF-5 using the AdEasy-1 adenovirus vector system. On Days 3, 7, 14, and 21, the contents of the sulfated glycosaminoglycan （sGAG）, deoxyribonucleic acid （DNA） and hydroxyproline （Hyp）, synthesis of proteoglycan and collagen II, gene expression of collagen II and aggrecan, and NP cell proliferation were assessed. Results： The adenovirus was an effective vehicle for gene delivery with prolonged expression of GDF-5. Biochemical analysis revealed increased sGAG and Hyp contents in human NP cells infected by Ad-GDF-5 whereas there was no conspicuous change in basal medium （BM） or Ad-green fluorescent protein （GFP） groups. Only cells in the Ad-GDF-5 group promoted the production of ECM, as demonstrated by the secretion of proteoglycan and up-regulation of collagen II and aggrecan at both protein and mRNA levels. The NP cell proliferation was significantly promoted. Conclusions： The data suggest that Ad-GDF-5 gene therapy is a potential treatment for IDD, which restores the functions of degenerative intervertebral disc through enhancing the ECM production of human NP ceils.

The inhibitory activities of Urtica fissa to BPH

In the present study, the BPH inhibitory activities of Urtica fissa were systematically investigated. Firstly, inhibitory activities of 5α reductase of the alcoholic extracts from different parts(root, stem, leaf, flower and fruit) were evaluated. The results indicated that the root possessed the most significant action. Subsequently, U. fissa root(UFR) was subjected to further pharmacological evaluation using the benign prostate hyperplasia(BPH) model rats induced by testosterone propionate. The results revealed that UFR could significantly decrease the prostate index, alter the hyperplasia tissue morphology, suppress the prostatic growth factors of VEGF, EGF, bF GF and KGF, decrease the inflammation factor levels of TNF-α, IL-1β and IL-6, improve the activities of GSH-Px, CAT and SOD and decrease the MDA level in the prostate of the model rats. Moreover, UFR also significantly suppressed the hormone levels of testosterone and dihydrotestosterone. These results indicated that the possible BPH inhibitory mechanisms of UFR were growth factor suppression, hormone level modulation, anti-inflammation, and anti-oxidative stress.