血管内皮生长因子C及其受体3在宫颈癌组织中的表达及意义

目的探讨血管内皮生长因子-C(VEGF-C)及其受体3在宫颈癌中的表达及其与癌周淋巴管生成、淋巴结转移的关系。方法采用免疫组化二步法检测55例宫颈癌组织中VEGF-C、VEGFR-3的表达情况。结果宫颈癌组织VEGF-C、VEGFR-3阳性率分别为69.1%、61.8%。VEGF-C与VEGFR-3阳性率在淋巴结转移、低分化组织中均明显升高(均P<0.05)。淋巴结转移的宫颈癌组织中淋巴管密度(LMVD)明显升高(P<0.01)。VEGF-C、VEGFR-3阳性的患者有明显预后不良的趋势。结论VEGF-C通过受体VEGFR-3在宫颈癌发生盆腔淋巴结转移中发挥重要作用。     

VEGFR-3在早期宫颈癌进展过程中的作用

目的:探讨VEGFR-3在早期宫颈癌进展过程中的作用。方法:免疫组织化学法检测41例早期子宫颈癌(ⅠA～ⅡA)组织中VEGF-C、VEGF-D、VEGFR-3的表达,同时检测VEGFR-3标记的脉管密度(MVD),分析其与临床病理因素的关系。结果:(1)VEGFR-3除于淋巴管内皮细胞表达外,部分血管内皮细胞也有表达。形态学上VEGFR-3阳性脉管部分为血管,部分为淋巴管,主要分布于肿瘤组织周围间质中。肿瘤细胞中可见VEGF-C、VEGF-D、VEGFR-3蛋白表达,其表达阳性率分别为48.7%(20/41)、58.5%(24/41)、63.4%(26/41);(2)肿瘤细胞中VEGFR-3蛋白表达与宫颈癌患者月经状态、组织学分级、组织学类型无关,与临床分期、淋巴结转移、淋巴管浸润及VEGF-C、D蛋白表达相关;MVD与月经状态、组织学分级、组织学类型、淋巴结转移、淋巴管浸润均无关,与临床分期及VEGF-C、D蛋白表达相关。结论:VEGFR-3可能通过促进肿瘤血管生成和淋巴管生成,参与了早期宫颈癌的恶性进展。     

Preoperative work-up of early cervical cancer (stages Ib-IIa)

OBJECTIVE: To determine the effectiveness of preoperative investigations in early cervical cancer. MATERIALS: We retrospectively reviewed the medical records of 309 patients with previously untreated early cervical carcinoma who completed pretreatment evaluation at "St. Savas" Cancer Hospital of Athens and "Metaxas" Memorial Hospital of Peireas between January 1986 and September 1, 2000. Ages ranged from 18-77 years old with a mean age of 48 and S.D. of 12.25. FIGO staging was Ib (200 pts.), IIa (105 pts.), IV (4 pts.). Histologic type was squamous (267 pts.), adenoid (35 pts.), adenosquamous (7 pts.). The patients were clinically examined and routinely evaluated with blood work-up, chest X-ray, IVP, abdominal CT scan, barium enema, sigmoidoscopy, cystoscopy, and/or urine cytology. Patients with early stage cervical carcinoma were treated with Wertheim-Meigs radical hysterectomy and pelvic lymphadenectomy, while those with advanced stage cervical carcinoma were treated with radiotherapy and chemotherapy. RESULTS: In urinary tract investigation, CT showed a sensitivity of 100% and a specificity of 99.67%. In gastrointestinal tract investigation CT showed a sensitivity of 50% and a specificity of 99.67%. When we compared the histologic findings of the pelvic lymph nodes that were extracted in surgically treated patients with the preoperative CT findings, we found that CT had a sensitivity of 63.33% and a specificity of 88.57%. CONCLUSION: In our series of patients with early stage cervical carcinoma, imaging and endoscopic tests added limited information over pelvic examination and altered in four cases (1.29%) the choice of the appropriate treatment modality. CT scans proved adequate in this series of patients in the evaluation of the bladder and colon. All other tests could have been performed only when CT was suspicious of invasion. Moreover, CT served as a baseline examination for future comparative studies in the follow-up of patients.     

Studies on the influence of interleukin 2 (IL-2) on antitumor effector mechanisms in patients with cervical cancer

Changes in DNA synthesis, lymphocyte subsets and various killer activities in peripheral blood mononuclear cells (PBMC) after IL-2 incubation were studied to analyze the influence of IL-2 on the antitumor effector mechanisms in cervical cancer patients. The results were as follows. DNA synthesis was advanced. Decrease in the OKT4/OKT8 ratio and diminished decrease in Leu7 were observed. NK activity was significantly lower than that in the control. LAK activity was almost equal to that in the control. Both activities and the killer action on autologous tumor significantly rose after IL-2 incubation. After operation, NK activity tended to be reduced for one or two weeks, but returned to the normal range by the 4th week in almost all cases. LAK activity was nearly within the normal range. Both activities after IL-2 incubation were at the same levels as before operation. A tendency to a fall in NK and LAK activities was observed under radiation therapy. Both activities after IL-2 incubation were lower than those before radiation therapy. These results suggest that IL-2 may be applied as an adjuvant immunotherapy following surgical operation and, though more difficulties are anticipated, applied to radiation therapy of cervical cancer.     

Residual cervical stump cancer (true cancer) and residual cancer of the cervical stump (coincident cancer). Casuistics and therapeutic results in the period 1955-1979

176 cases of cervical stump cancer have been reviewed. "Coincident cancer" and "True cancer" distinction has been made. Histological features, therapeutic plane and survival have been reported.     

Sentinel node detection in cervical cancer with (99m)Tc-phytate

OBJECTIVES: The aim of this study was to investigate the feasibility of sentinel lymph node (SLN) identification using radioisotopic lymphatic mapping with technetium-99 m-labeled phytate in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. METHODS: Between July 2001 and February 2003, 56 patients with cervical cancer FIGO stage I (n = 53) or stage II (n = 3) underwent sentinel lymph node detection with preoperative lymphoscintigraphy ((99m)Tc-labeled phytate injected into the uterine cervix, at 3, 6, 9, and 12 o'clock, at a dose of 55-74 MBq in a volume of 0.8 ml) and intraoperative lymphatic mapping with a handheld gamma probe. Radical hysterectomy was aborted in three cases because parametrial invasion was found intraoperatively and we performed only sentinel node resection. The remaining 53 patients underwent radical hysterectomy with complete pelvic lymphadenectomy. Sentinel nodes were detected using a handheld gamma-probe and removed for pathological assessment during the abdominal radical hysterectomy and pelvic lymphadenectomy. RESULTS: One or more sentinel nodes were detected in 52 out of 56 eligible patients (92.8%). A total of 120 SLNs were detected by lymphoscintigraphy (mean 2.27 nodes per patient) and intraoperatively by gamma probe. Forty-four percent of SLNs were found in the external iliac area, 39% in the obturator region, 8.3% in interiliac region, and 6.7% in the common iliac area. Unilateral sentinel nodes were found in thirty-one patients (59%). The remaining 21 patients (41%) had bilateral sentinel nodes. Microscopic nodal metastases were confirmed in 17 (32%) cases. In 10 of these patients, only SLNs had metastases. The 98 sentinel nodes that were negative on hematoxylin and eosin were submitted to cytokeratin immunohistochemical analysis. Five (5.1%) micrometastases were identified with this technique. The sensitivity of the sentinel node was 82.3% (CI 95% = 56.6-96.2) and the negative predictive value was 92.1% (CI 95% = 78.6-98.3). The accuracy of sentinel node in predicting the lymph node status was 94.2%. CONCLUSION: Preoperative lymphoscintigraphy and intraoperative lymphatic mapping with (99m)Tc-labeled phytate are effective in identifying sentinel nodes in patients undergoing radical hysterectomy and to select women in whom lymph node dissection can be avoided.     

外源性三磷酸腺苷对高表达P2X7受体的宫颈癌Caski细胞生长的影响

目的:探讨外源性三磷酸腺苷(ATP)对高表达P2X7受体的人宫颈癌Caski细胞(Caski-P2X7)生长及凋亡的影响,为临床应用提供理论依据。方法:选择本实验室建立的Caski-P2X7细胞和对照Caski-3.1细胞(转染空载体质粒),用不同浓度ATP分别处理两种细胞株,MTT法检测细胞生存率,荧光染色法检测线粒体膜电位,流式细胞术检测细胞凋亡率;用2.5mmol/L ATP处理两种细胞后,Western blot检测凋亡相关蛋白(细胞色素C,bcl-2,Bax)的变化。结果:不同浓度ATP作用后,两种细胞生存率及线粒体膜电位均降低,而细胞凋亡率升高,均呈浓度依赖性;同一浓度ATP作用后,Caski-P2X7细胞生存率及线粒体膜电位均显著低于Caski-3.1细胞(P<0.05),但细胞凋亡率显著高于Caski-3.1细胞(P<0.05)。2.5mmol/L ATP处理后,Caski-P2X7细胞胞质中细胞色素C及凋亡蛋白Bax表达量明显增加(P<0.05),而抗凋亡蛋白bcl-2表达量明显减少(P<0.05)。结论:一定浓度的ATP可通过P2X7受体途径诱导宫颈癌Caski细胞凋亡。     

A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells

ObjectiveCervical cancer is the second most common female cancer worldwide, and it remains a challenge to manage preinvasive and invasive lesions. Food-based cancer prevention entities, such as black raspberries and their derivatives, have demonstrated a marked ability to inhibit preclinical models of epithelial cancer cell growth and tumor formation. Here, we extend the role of black raspberry-mediated chemoprevention to that of cervical carcinogenesis.MethodsThree human cervical cancer cell lines, HeLa (HPV16?/HPV18+, adenocarcinoma), SiHa (HPV16+/HPV18?, squamous cell carcinoma) and C-33A (HPV16?/HPV18?, squamous cell carcinoma), were treated with a lyophilized black raspberry ethanol extract (RO-ET) at 25, 50, 100 or 200 μg/ml for 1, 3 and 5 days, respectively. Cell proliferation was measured by WST1 (tetrazolium salt cleavage) assays. Flow cytometry (propidium iodide and Annexin V staining) and fluorescence microscopy analysis were used to measure apoptotic cell changes.ResultsWe found that non-toxic levels of RO-ET significantly inhibited the growth of human cervical cancer cells, in a dose-dependent and time-dependent manner to a maximum of 54%, 52% and 67%, respectively (p < 0.05). Furthermore, cell growth inhibition was persistent following short-term withdrawal of RO-ET from the culture medium. Flow cytometry and fluorescence microscopy demonstrated RO-ET-induced apoptosis in all cell lines.ConclusionBlack raspberries and their bioactive components represent promising candidates for future phytochemical-based mechanistic pathway-targeted cancer prevention strategies.     

Metabolic risk factors and cervical cancer in the metabolic syndrome and cancer project (Me-Can)

Background

Little is known about the association between metabolic risk factors and cervical cancer carcinogenesis.

Material and methods

During mean follow-up of 11 years of the Me-Can cohort (N = 288,834) 425 invasive cervical cancer cases were diagnosed. Hazard ratios (HRs) were estimated by the use of Cox proportional hazards regression models for quintiles and standardized z-scores (with a mean of 0 and a SD of 1) of BMI, blood pressure, glucose, cholesterol, triglycerides and MetS score. Risk estimates were corrected for random error in the measurements.

Results

BMI (per 1SD increment) was associated with 12%, increase of cervical cancer risk, blood pressure with 25% and triglycerides with 39%, respectively. In models including all metabolic factors, the associations for blood pressure and triglycerides persisted. The metabolic syndrome (MetS) score was associated with 26% increased corrected risk of cervical cancer. Triglycerides were stronger associated with squamous cell carcinoma (HR 1.48; 95% CI, 1.20-1.83) than with adenocarcinoma (0.92, 0.54-1.56). Among older women cholesterol (50-70 years 1.34; 1.00-1.81), triglycerides (50-70 years 1.49, 1.03-2.16 and ≥ 70 years 1.54, 1.09-2.19) and glucose (≥ 70 years 1.87, 1.13-3.11) were associated with increased cervical cancer risk.

Conclusion

The presence of obesity, elevated blood pressure and triglycerides were associated with increased risk of cervical cancer.     

Intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer

Objectives

To report the intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer.

Tamoxifen and proliferation of vaginal and cervical epithelium in postmenopausal women with breast cancer

Objective: The estrogenic effect of tamoxifen on vaginal and cervical epithelium in postmenopausal women with breast cancer is evaluated. Study Design: The tamoxifen group consisted of 92 postmenopausal breast cancer patients, the control group I of 30 postmenopausal women with breast cancer receiving no endocrine therapy and the control group II of 40 postmenopausal women without primary breast cancer taking no hormones. We determined the maturation index and the incidence of endocervical cell hyperplasia and metaplasia in cervical and vaginal smears. Results: The maturation index increased under tamoxifen within the first 24 months from 0.4011 before taking tamoxifen (n = 56) to 0.6039 (n = 138, P<0.0001). The maturation index in the group treated with tamoxifen was statistically significantly higher (P<0.0001) than in the control groups (control group I: 0.3975, P<0.0001; control group II: 0.4102, P<0.0001). Under therapy with tamoxifen endocervical cell hyperplasia (P=0.00156) and metaplasia (P=0.00123) appeared significantly more often. Conclusion: An apparent increase not only of the incidence of endocervical cell hyperplasia and metaplasia but also of the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen could be demonstrated.