Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Hormone Secretion by Cell Culture of Human GH-PRL Secreting Pituitary Adenomas: Effects of Bromocriptine

Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.

Factors influencing improvement of visual field after trans-sphenoidal resection of pituitary macroadenomas:a retrospective cohort study

AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visual field defect induced by pituitary macroadenomas. All of them were treated with trans-sphenoidal surgery. Ophthalmologic evaluation, best -corrected visual acuity (BCVA), and visual field examination were performed before and 3mo after surgery. BCVA, visual field defect index mean deviation (MD), duration of symptoms, age, sex, and volume of tumors were compared. Expression of vascular endothelial growth factor (VEGF) and Ki-67 of tumor tissue were detected by immunohistochemical technique. RESULTS: The mean age of patients was 44.23 +/- 1.29y. Ninety -three patients were female and 108 were male. The mean tumor volume was 14.36 +/- 6.23 cm(3). The mean duration of preoperative symptoms was 11.50 +/- 0.88mo. Mean preoperative MD was -17.50 +/- 0.82 dB. Mean Preoperative visual acuity was 0.64 +/- 0.04. Postoperative visual field improved in 270 (73.77%) eyes, unchanged in 96 (26.23%) eyes. Multivariate logistic regression displayed that the factors independently influencing visual field improvement were young age (OR=1.71, 95%CI: 1.325-2.387, P=0.013), low preoperative MD absolute value (OR=1.277, 95%CI: 1.205-1.355, P<0.001), small volume of tumor (OR=1.458, 95%CI: 1.060-4.289, P<0.001), low expression of VEGF in tumor tissue (OR=1.554, 95%CI: 1.089-2.457, P=0.022), and low expression of Ki-67 in tumor tissue (OR=1.552, 95%CI: 1.161-2.847, P=0.026). CONCLUSION: After pituitary macroadenomas trans sphenoidal resection, the independent influencing factors of the visual fields recovery were low preoperative MD absolute value, young age, small volume of tumor, and expression levels of VEGF/Ki-67.

ELEVATED SOLUBLE EPIDERMAL GROWTH FACTOR RECEPTOR LEVEL IN PITUITARY ADENOMA AND CARCINOMA

To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.

Ultrastructural and Immunoelectron Microscopical Study of Human Pituitary Somatotroph Adenomas and Prolactinomas

Nowdays the application of immunohistochemical techniques and ultrastructuralanalysis and correlation with clinical and biochemical findings have led to a moredetailed functional classification,in which growth hormone (GH)-producing andprolactin (PRL)-producing adenomas have been shown to comprise more than halfof pituitary adenomaso.Few immunoelectron microscopic studies on GH and PRLadenomas have been made,however,in limited cases so far,though a numberof authors have described the characteristics of pituitary adenomas by conventionalelectron microscopy.In addition to routine electron microscopy,immuno-.electron microscopical technique using protein A-gold probes was applied in

THE ROLE OF CALCIUM ION IN THE PATHOGENESIS OF HUMAN PITUITARY GH－SECRETING ADENOMAS

To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.

The etiology,clinical features and medical treatment of somatotroph adenomas

Somatotroph adenomas lead to hypersecretion of growth hormones(GH)and may cause mass effects.Patients with somatotroph adenomas may present with acral and soft tissue enlargement,joint pain,heart and respiratory failure,diabetes mellitus and hypertension,resulting in increased morbidity and mortality.Early diagnosis and treatment are therefore important in prolonging life and improving quality of life.Recent studies depicted the landscape of genetic and epigenetic changes in sporadic somatotroph adenomas.New approaches are being developed for genetic testing,diagnosis and surveillance,which are helpful in early diagnosis,treatment and disease control of somatotroph adenomas.Data suggest that patients with somatotroph adenomas are best treated with multidisciplinary teams composed of neuro-endocrinologists,neurosurgeons,radiation oncologists and other specialists.This mini-review summarizes in a concise way the up-to-date discussion on the etiology,new diagnostic techniques and novel treatments of somatotroph adenomas.

Phosphatase and tensin homology deleted in chromosome 10,hypoxia-inducible factor-1 alpha gene expression in colorectal adenoma and adenocarcinoma and their relation to vascular endothelial growth factor protein expression

To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.

Small intestinal tubular adenoma in a pediatric patient with Turner syndrome

Turner syndrome (TS) is a female chromosomal disorder caused by the lack of an X chromosome. The loss of this chromosome may result in the deficiency of tumorsuppressive or DNA repair genes, leading to tumorigenesis. Recombinant human growth hormone (GH) has been popularly used for treatment in TS patients for growth promotion. Although treatment with GH has been correlated with precancerous and cancerous lesions in TS children, its associations with gastric or colonic tumors, especially ileal tubular adenomas, have not been reported frequently. We here report a case of a 16-year-old patient with TS and tubular adenoma of the small intestine. Whether the ileal adenoma was caused by TS itself or GH therapy was discussed.

TPA Enhances Growth Horm one (GH) Secretion Effect ofGH-Releasing Horm one (GHRH) by Hum an gsp-PositivePi-tuitary Som atotrophinom as

In recent years, one of the most exciting advances in the researches of pituitary adenomas is the discovery that 30 %-40 % of human pituitary somatotrophinomas carry somatic mutations of the gene for the α subunit of the stimulatory GTP binding protein, G s (G sα). These mutations, termed gsp oncogenes, may play an important role in the tumorigenesis of pituitary adenomas. Of 10 somatotrophinomas examined, 3 (30 %) were proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction (PCR). GHRH exerted a significant stimulatory effect on GH secretion in 2 of 3 gsp positive and 4 of 7 gsp negative tumors. Moreover, phorbol ester, 1, 2 tetradecanoylphorbol 13 acetate (TPA), enhanced stimulation of lated the GH secretion effect exerted by GHRH in gsp positive somatotrophinomas, whereas this effect was not observed in gsp negative tumors. This result suggests that the protein kinase C signal system as well as adenylyl cyclase cAMP protein kinase A intracellular signal transduction system plays a pivotal role in GH secretory control of GHRH, which may work together via a cross talk mechanism.

Bronchiolar adenoma with unusual presentation:Two case reports

BACKGROUND The clinicopathological features,immunohistochemical characteristics,and genetic mutation profile of two unusual cases of distal bronchiolar adenoma are retrospectively analyzed and the relevant literature is reviewed.CASE SUMMARY Case 1 was a 63-year-old female patient who had a mixed ground-glass nodule,with mild cells in morphology,visible cilia,and bilayer structures in focal areas.Immunohistochemical staining for P63 and cytokeratin(CK)5/6 revealed the lack of a continuous bilayer structure in most areas,and no mutations were found in epidermal growth factor receptor,anaplastic lymphoma kinase,ROS1,Kirsten rat sarcoma,PIK3CA,BRAF,human epidermal growth factor receptor-2(HER2),RET,and neuroblastoma RAS genes.Case 2 was a 58-year-old female patient who presented with a solid nodule,in which most cells were observed to be medium sized,the nuclear chromatin was pale and homogeneous,local cells had atypia,and cilia were found locally.Immunohistochemical staining for P63 and CK5/6 showed no expression of these proteins in mild cell morphology whereas the heteromorphic cells showed a bilayer structure.The same nine genes as above were analyzed,and HER2 gene mutation was identified.CONCLUSION Some unresolved questions remain to be answered to determine whether the lesion is a benign adenoma or a part of the process of malignant transformation from benign adenoma of the bronchial epithelium.Furthermore,whether lesions with atypical bilayer structures are similar to atypical hyperplastic lesions of the breast remains to be elucidated.Moreover,clarity on whether these lesions can be called atypical bronchiolar adenoma and whether they are invasive precursor lesions is needed.Future studies should examine the diagnostic significance of HER2 gene mutation as a prognostic indicator.

3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术应用效果及对血清MMP-9和IGF-1水平的影响

目的:探究3D打印技术在经鼻蝶窦入路垂体腺瘤(PA)切除术的应用效果及对血清基质金属蛋白酶-9(MMP-9)和胰岛素样生长因子-1(IGF-1)水平的影响。方法:选取2020年5月至2022年5月秦皇岛市第一医院收治的84例PA患者,按照随机数表法将其分为观察组和对照组,每组42例。对照组行经鼻蝶窦入路垂体腺瘤切除术,观察组行经鼻蝶窦入路垂体腺瘤切除术联合应用3D打印技术,比较两组肿瘤切除效果、围术期指标、视力改善情况、MMP-9和IGF-1水平,以及鼻腔功能的鼻气道阻力(NAR)、T&T嗅觉测试评分及并发症。结果:观察组肿瘤切除效果优于对照组,差异有统计学意义(U=2.286,P<0.05);观察组手术时间、术中出血量及住院时间均少于对照组,差异有统计学意义(t=4.780、11.438、11.842,P<0.05);术后3 d、7 d时观察组血清MMP-9和IGF-1水平低于对照组,差异有统计学意义(F=7.526、4.985,P<0.05);术后1个月、3个月时观察组NAR及T&T嗅觉测试评分低于对照组,差异有统计学意义(F=6.359、8.436,P<0.05);两组视力视野改善情况及并发症发生率比较,差异无统计学意义(P>0.05)。结论:3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术可提高肿瘤切除效果,优化手术操作,减少创伤,有利于减轻疼痛,改善嗅觉功能与视力视野,并能降低血清MMP-9、IGF-1水平,且安全性较高。

MMP-9与IGF-1在垂体腺瘤患者中的表达及其临床预测价值

目的探究MMP-9与IGF-1在垂体腺瘤患者中的表达及其临床预测价值。方法回顾性分析84例垂体腺瘤患者临床资料,分析不同病理垂体腺瘤患者的血清指标[基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)]水平差异。84例垂体腺瘤患者依据治疗后肿瘤直径大小和转移率分为缓解组(n=40)与未缓解组(n=44),采用受试者工作特征(ROC)曲线分析MMP-9、IGF-1对垂体腺瘤患者预后的评估效能。结果不同肿瘤直径的垂体腺瘤患者MMP-9、IGF-1水平比较无显著性差异(P>0.05);未发生淋巴结转移的患者MMP-9水平明显低于发生转移的患者,而IGF-1水平高于发生转移的患者,差异有统计学意义(P<0.05);临床分期为Ⅰ~Ⅱ期的垂体腺瘤患者MMP-9水平明显低于Ⅲ~Ⅳ期患者,而IGF-1水平高于Ⅲ~Ⅳ期患者,差异有统计学意义(P<0.05)。缓解组患者MMP-9低于同期未缓解组,IGF-1水平明显高于同期未缓解组患者,差异有统计学意义(P<0.05)。ROC曲线结果显示血清中MMP-9与IGF-1的截断值分别为16.61 ng/L、229.06 ng/L,MMP-9预测ROC曲线下面积(AUC)为0.871(95%CI=0.778~0.935),敏感度75.61%,特异度92.50%,IGF-1预测ROC曲线AUC为0.851(95%CI=0.755~0.921),敏感度75.61%,特异度87.50%。结论血清中MMP-9,IGF-1水平与垂体腺瘤患者临床病理特征及预后情况密切相关,可通过早期检测结果进一步优化诊治措施。

Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas

Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas （GHPA） is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal surgery. Epidermal growth factor-like domain 7 （EGFL7） is a secreted factor implicated in tumor angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed that the expression level of EGFL7 and p-EGFR in invasive GHPA was much higher than that ofnon-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR （p-EGFR）. Noticeably, EGFL7 knockdown sig- nificantly inhibited activation of EGFR signaling cascades, including p-ERGR, p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478, significantly suppressed migration and invasion of GH3 and GTI-1 cells. In summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR signaling pathway and plays an important role in migration and invasion of invasive GHPA.

胰岛素样生长因子-1在脑垂体腺瘤中的表达及临床意义

目的分析垂体腺瘤患者血清中胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)的表达并按照不同标准进行分组比较,探讨IGF-1在垂体腺瘤中的表达及其临床意义。方法选取2019年1月~2021年6月昆明医科大学第二附属医院收治的156例垂体腺瘤作为试验组,选取同期健康体检者22例作为对照组。采用磁微粒化学发光法测定血清IGF-1水平。综合磁共振成像(magnetic resonance imaging,MRI)测量所得最大径与术后肿瘤病理标本所得肿瘤最大径,将试验组按照不同临床特征进行分组,比较各亚组及对照组的IGF-1水平差异。结果生长激素细胞腺瘤、双激素和多激素细胞腺瘤患者IGF-1水平高于对照组及其余类型,差异均有统计学意义(P<0.05);巨腺瘤患者IGF-1水平高于对照组及其余类型,差异有统计学意义(P<0.05);侵袭性垂体腺瘤患者IGF-1水平高于非侵袭性患者及对照组,差异有统计学意义(P<0.05)。Logistic回归分析结果表明,IGF-1水平和肿瘤最大径为垂体腺瘤有侵袭性的危险因素,且IGF-1水平越高、肿瘤最大径越大,侵袭性风险越高;垂体腺瘤患者术后1个月内的IGF-1水平相较于术前有明显降低,差异有统计学意义(P<0.05)。结论IGF-1对不同功能类型垂体腺瘤的鉴别诊断、对垂体腺瘤早期侵袭性判断有一定价值,并有望作为术后随访的一项可信指标。

200例垂体GH腺瘤经蝶手术疗效观察

１９７９年７月～１９９２年３月共施行经蝶显微外科切除垂体ＧＨ腺瘤２１２例，其中２００例有术前后ＧＨ测定对比，大腺瘤１３２例，微腺瘤６８例。１９８６年后的１３８例在手术方法上进行了改进。本组总治愈缓解率为７２．５％，其中大腺瘤的治疗缓解率从１９８６年前的３１．４％提高到６９．１％；微腺瘤从４４．４％提高到８０．５％。１例手术中出现心脏意外死亡，死亡率为０．５％。ＧＨ水平动态观察结果显示，术后２周内ＧＨ水平与以后的ＧＨ水平基本一致，故认为术后２周ＧＨ水平可作为判断手术疗效的主要指标。本文对影响疗效的诸因素及术后常见并发症的防治进行了讨论。

EGFR和VEGF在乳腺癌中表达的临床意义

目的:探讨表皮生长因子受体(Epidermal group pactor,EGFR)和血管内皮生长因子(Vascalia endothelial grouth factor,VEGF)在乳腺癌中表达状况及临床意义。方法:收集乳腺癌标本86例、腺瘤46例。利用免疫组织化学技术检测EGFR和VEGF阳性表达率,并分析它们之间的相关性。结果:EGFR和VEGF在乳腺腺瘤中阳性率为13.04%(6/46)和34.78%(16/46);它们在乳腺癌中阳性率前者为56.98%(49/86),后者为54.65%(47/86),两者差异无显著性(P>0.05)。它们在乳腺癌中的阳性率明显高于腺瘤中的阳性率(P<0.05);在浸润型癌组(含小叶癌或导管浸润癌)的阳性率明显高于非浸润型癌组(含小叶及导管内癌)。在有淋巴结转移组阳性率明显高于无转移组(P<0.05)。结论:EGFR和VEGF高表达与乳腺癌发生及转移有相关性,而且两者呈正相关。检测乳腺癌EGFR和VEGF对靶向化学治疗有指导作用。

生长激素瘤患者临床特征的回顾性分析

目的分析生长激素瘤(GH瘤)患者的临床特征,并总结其诊治经验。方法收集1990年1月-2016年12月在解放军总医院就诊的338例GH瘤患者的临床资料,回顾性分析其中病例资料较完整的252例患者的一般情况、病史资料、实验室及辅助检查结果、治疗方式及结果等,并对其中部分患者的疾病缓解情况进行随访。结果我院GH瘤患者收治数量逐年增加,近3年收治患者例数占总收治患者例数56.2%;GH瘤患者男女比例约为1:1,就诊年龄呈正态分布,41~50岁发病人数最多;GH瘤患者最常见的临床体征为手、足增大(60.7%),其次为鼻翼增大(35.7%),最常见的临床症状为头痛(42.5%),其次为视力、视野改变(26.6%);GH瘤患者最常见的临床并发症为糖代谢异常(72.6%),呼吸睡眠暂停、甲状腺肿或结节、心功能异常及结肠息肉发生率均明显上升(69.5%、56.4%、57.0%及54.1%),上述并发症检查患者例数分别占本研究总患者例数的42.1%、23.4%、37.3%、47.6%和14.7%;GH 23.37±1.42μg/L,IGF-1 804.28±273.93ng/ml;垂体GH瘤85.0%为大腺瘤;手术治疗仍为一线治疗方案,选择药物治疗患者较少;随访率38.0%(84/252),随访患者缓解率40.5%;术后早期GH水平判断手术长期缓解的阳性率与真实随访手术长期缓解的阳性率基本一致(χ2=3.368,P>0.05)。结论近年收治GH瘤患者数量不断增加,临床常见体征和症状分别为肢端肥大和头痛;对本病并发症的筛查尚不系统,存在大量遗漏,仍须加强患者治疗后随访,以改善患者生存质量;术后早期GH水平测定对手术预后有较高预测价值。

RegⅣ、EGFR和Survivin在结直肠腺瘤癌变过程中的表达及意义

目的研究再生基因Ⅳ(RegⅣ)、表皮生长因子受体(EGFR)及Survivin在结直肠腺瘤癌变过程中的表达,并分析其与结直肠腺瘤及结直肠癌临床病理特征的关系。方法采用免疫组织化学结合组织芯片法检测结直肠正常黏膜(150例)、腺瘤(77例)、结直肠癌(150例)RegⅣ、EGFR及Survivin的表达,并分析其与临床病理特征的关系。结果 RegⅣ、EGFR、Survivin在结直肠正常黏膜、腺瘤及癌组织中,表达逐渐升高,差异有统计学意义(P<0.05)。RegⅣ、Survivin与结直肠腺瘤大小及分级相关,EGFR仅与腺瘤的分级相关;RegⅣ、EGFR与结直肠癌的分化程度、淋巴结转移及TNM分期密切相关,Survivin与结直肠癌的淋巴结转移及TNM分期密切相关(P<0.05),而3者与结直肠癌患者的性别、年龄、肿瘤大小及浸润深度无关(P>0.05)。结直肠腺瘤组织内RegⅣ、EGFR、Survivin 3者无相关性(P>0.05);结直肠癌组织内RegⅣ与EGFR、RegⅣ与Survivin、EGFR与Survivin表达呈正相关(P<0.05)。结论 RegⅣ、EGFR及Survivin在结直肠腺瘤癌变过程中逐渐升高,提示3者共同参与结直肠腺瘤癌变的发生,且与结直肠癌的TNM分期密切相关,联合检测有利于对结直肠癌的预后进行评估,并为研发靶向药物提供理论支持。

白介素-2促进RC-4B/C垂体瘤细胞系增殖

采用细胞培养方法 ,以3 H TdR掺入率反映细胞增殖水平 ,研究了白介素 2 (IL 2 )对大鼠源的RC 4B/C垂体瘤细胞系增殖的影响 ,并初步分析了IL 2的作用机制。结果表明 :(1)IL 2 (10～ 10 0 0U/ml)剂量依赖性地显著提高RC 4B/C细胞3 H TdR掺入率。(2 )特异性酪氨酸蛋白激酶 (PTK)抑制剂tyrphostin (1μmol/L)可明显降低RC 4B/C细胞3 H TdR掺入率 ,并可部分阻断IL 2的促细胞增殖作用。(3)特异性蛋白激酶A (PKA)抑制剂H 9(1μmol/L)作用后 ,3 H TdR掺入率明显升高 ;H 9还可加强IL 2的促细胞增殖作用。(4)在本实验中未观察到抗雌激素tamoxifen (1μmol/L)对IL 2促RC 4B/C细胞增殖效应有明显影响。上述结果表明 ,IL 2参与调节垂体瘤细胞的增殖活动 ,并且IL 2的作用与PTK及PKA信号传导途径有关。