妇科养荣胶囊配合平消片治疗晚期子宫颈癌60例

1对象和方法1．1对象本组60例晚期子宫颈癌患者均经影象学、细胞学及病理学等检查确诊。其中手术后复发12例，放疗后18例，化疗后13例，放疗加化疗后17。按照目前被普遍采用的子宫颈癌FJJO分期（1995年修订），Ⅲ期38例，Ⅳ期22例。1．2方法1．2．1服药方法按门诊先后随机分为治疗组30例和对照组30例，治疗组刚妇科养荣胶囊（西安阿房宫药业有限公司生产，国药准字Z20050381），

子宫颈癌放射治疗后发子宫内膜癌临床分析

目的:分析宫颈癌放射治疗后发子宫内膜癌的临床特点。方法:回顾性分析6例宫颈癌放射治疗后发子宫内膜癌患者的临床资料。结果:诊断子宫内膜癌的中位年龄为61岁,放疗后子宫内膜癌的中位时间为15年。以无症状及腹痛患者4例(66.6%),术6前确诊者1例(16.6%)。手术分期为I b期2例,I C期2例,II b期l例,IIIc期1例,IV期1例。5例中分化以上。复发时间平均29个月。3年、5年生存率分别为33.3%、0%。结论:宫颈癌放射后发子宫内膜癌术前早期诊断困难,预后差。

调强放疗在子宫颈癌中的研究进展

放射治疗是子宫颈癌治疗中的重要方式之一,传统体外放疗方式为全盆2野对穿放疗和(或)4野放疗,此种照射野包含了小肠、直肠、膀胱、脊髓等,导致消化系统、泌尿系统等急慢性并发症发生率较高,严重影响了患者的生活质量。调强放疗具有分别调节肿瘤靶区和降低邻近危及器官剂量的优势,使宫颈癌术后补充放疗、主动脉旁淋巴结转移的根治性放疗等成为可能,同时很好地保护了危及器官,临床近期疗效满意,毒副反应可以耐受。

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

AIM： To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy （IMRT） and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS： A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS： Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy （median： 64.8 Gy） to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume （PTV） of the gross tumor volume boost was 91.2%-98.2% of the prescription dose （standard deviation [SD]： 3.7%-5.7%）. The minimum dose received by the PTV Of the clinical tumor volume was 93.8%-104.8% （SD： 4.3%-11.1%） of the prescribed dose. With a median follow-up of 15 rno （range： 3-21 too）, all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. CONCLUSION： Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

Clinical study of paclitaxel plus cisplatin in the treatment of recurrent cervical cancer

Objective: To observe the efficacy and toxicities of paclitaxel plus cisplatin in the treatment of recurrent cervical cancer. Methods: Twenty-three patients with a diagnosis of recurrent cervical cancer were eligible. Three-weekly chemo- therapy regimen consisted of paclitaxel 135–150 mg/m2 infusion for 3 h on day 1, cisplatin 25 mg/m2 infusion on day 1 to 3. All patients received at least two cycles treatment. Results: The response rates was 47.8%, including CR 2 cases (8.7%), PR 9 cases (39.1%). The major toxicity included neutropenia, nausea vomiting, arthralgia, myalgia and alopecia. Conclusion: Paclitaxel combined with cisplatin is an effective therapy with acceptable adverse reactions for recurrent cervical cancer.

Malignant neoplasms of the uterus following radiation therapy for cervical carcinoma: a clinical study of 47 cases

Objective： To study the characteristics and clinical features of uterine neoplasms developed after radiation therapy for cervical carcinoma. Methods： Clinical data of 47 cases of uterine neoplasms occurred following radiation therapy for cervical carcinoma were retrospectively reviewed. Results： The median age at uterine neoplasms diagnosis was 62 years （range： 38-77 years）, and the median latency period from initial therapy to development of uterine neoplasms was 14 years （range： 5-35 years）. Thirty of 47 cases were endometrial carcinoma, of which 3 were uterine papillary serous carcinoma （UPSC）. Seventeen of 47 patients were uterine sarcoma, all of those were carcinosarcoma. The distribution by stage, grade, and histology of 30 cases of endometrial carcinoma was as follows： stage Ⅰb, 1 case; stage Ⅰc, 2 cases; stage Ⅱ, 6; stage Ⅲa, 4; stage Ⅲb, 2; stage Ⅲc, 11; stage Ⅳ, 4 cases; grade 1, two cases; grade 2, nine; grade 3 （include 3 UPSC patients）, seventeen; unknown grade, two; endometriod, 27; UPSC, 3 cases; 7 of 30 cases of endometrial carcinoma had recurrences （23.3%）, at median time to recurrence was 24 months, and their median survival time was 26 months. The overall 3- and 5-year survival rates were 60% and 38%, respectively. Of the 17 cases of uterine sarcoma, the median survival was 10 months, 6 patients occurred recurrence （35.9%）, at a median time to recurrence was 9 months, and their median survival was 6 months. The overall 3- and 5-year survival rates were 12% and 0, respectively. Conclusion： The main uterine neoplasms development after radiation therapy for cervical carcinoma is endometrial carcinomas, of which there is a preponderance of high-risk histological subtypes and a poor prognosis. Most of the uterine sarcomas occurred following radiation therapy for cervical carcinoma are carcinosarcomas and the prognosis is very poor.

Molecular mechanism of Skp2 in promoting cervical cancer HeLa cell proliferation

Objective: To explore the impact of s-phase kinase-associated protein 2 (Skp2) on cervical cancer cell proliferation and the relationship between Skp2 and expression of cell regulation factors and transcription factors. Methods: RNAi technology was used to silence Skp2 gene in HeLa cells. After interference, RT-PCR was used for detection of Skp-2 mRNA, and Western blotting and flow cytometry were used for protein expression analysis. Results: siRNA significantly inhibited HeLa cell proliferation (P<0.05) and increased HeLa apoptosis, and G1/G0 phase cells were increased significantly (P<0.01). Skp2 siRNA transfected HeLa cells effectively reduced Skp2 protein levels, while p27 and p-p53 protein levels were increased significantly. RT-PCR results showed that after interference Skp2 mRNA, c-myc mRNA and cyclin A mRNA expressions decreased significantly compared with those in control group (P<0.01), and p27mRNA expression level was significantly higher (P<0.01). Conclusion: The change of Skp2 expression affects the expression of the cell cycle protein, thus affecting proliferation and apoptosis of HeLa cells. Skp2 protein plays an important role in the progression of cervical cancer; yet the specific mechanism still needs further study.

The Analysis of High-Risk Molecular Markers for Cervical Cancer Patients under Thirty-Five

OBJECTIVE To explore molecular markers for cervical cancer in female patients below thirty-five years of age, so that the markers may be used to formulate a prognosis and to provide some useful targets for improving therapy. METHODS Pathological data were collected from 64 cervical cancer patients under the age of 35 from June, 1995 to June, 2000 in our institution. The data were retrospectively analyzed as a study group, and compared to data obtained from 90 cervical cancer cases over the age of 35 as controls who underwent treatment during the same time period. Immuno-histochemical and quantified image analyses were conducted to look for differences between the two groups in expression of survivin, p27, CD44v6, MMP-2 and TIMP-2. RESULTS The overall 5-year survival rate (65.6%) of the study group was significantly lower (P<0.05) compared to the control group (84.4%). The expression of survivin, MMP -2 and CD44v6 was much higher in the younger study group compared to the older control group, but TIMP-2 displayed higher expression in the control group (P<0.05). There was no significant difference in p27 expression between the two groups (P>0.05). CONCLUSION Young women patients with cervical cancer have a poorer prognosis compared to old women. Our study reveals that survivin, MMP-2, TIMP-2 and CD44v6 expression have a correlation with shorter 5-year survival. Improvement in the prognosis for young cervical cancer patients can be expected using biomedical therapy which targets these molecular markers.

Expression and Clinical Significance of HMGB1 and RAGE in Cervical Carcinoma

OBJECTIVE To study the expression level and clinical significance of HMGB1 and RAGE in cervical squamous epithelial carcinoma. METHODS Real time quantitative polymerase chain reaction （qRT-PCR） was employed to examine the expression of HMGB1 （high mobility group box protein1）, and RAGE （receptor for advanced glycation endproducts） in 60 cervical squamous epithelial carcinomas （CSEC）, their paraneoplastic tissues （PS） and 30 normal cervix tissues （NCS）. RESULTS The expression of HMGB1 in the CSEC samples and PS was similar （P〉0.05）, but higher compared to NCS （P〈0.05）. Overexpression of HMGB1 in the CESC tissues was significantly correlated with the tumor （P〈0.05）, and the presence of metastasis （P〈0.01）, but not correlated with the tumor diameter or tumor grade.RAGE expression was not significantly different among these tissue types, and showed no significant correlation with the the tumor stage, diameter or grade. But there was a significant positive correlation between RAGE expression and CSEC metastasis. CONCLUSION The results suggest that HMGB1 may be related to the proliferation, progression and metastasis of CSEC. The relationship of HMGBI/RAGE may be of importance for CSEC metastasis. HMGB1 presents a new potential gene target for prevention and treatment of CSEC. Study of HMGBI/RAGE expression will offer an experimental foundation for understanding the pathogenesis of CSES.

Overexpression of p53 Gene in Esophageal and Cervical Cancer and the Relationship with Radiotherapy Effects

Objective :To investigate the relationship between p53 -protein overexpression in esophageal and cervical squamous cell cancer and their clinical radiosensitivity. Methods: The immuno-histochemical assays were done for 52 cases with esophageal and cervical squamous cell cancer. The relationship between the assay results and short-term radiotherapy was investigated. Results: p53 overexpression was 52. 38% and 35. 48% respectively, in esophageal cancer and cervical cancer; p53 over-expression in high differentiated squamous cell cancer was lower than those in moderate and poor differentiated cases(P<0. 05). There was no relationship between p53 overexpression and stages(P> 0. 05). In the cases of cervical cancer, p53 overexpression had the less short-term effect(P< 0. 05), and In esophageal cancers, there was no relationship with radiotherapy effect(P>0. 05). Conclusion:This study suggests that y53 gene lias the certain relationship with tumor radiosensitivity.

Bone marrow-sparing intensity-modulated radiotherapy for postoperative treatment of cervical cancer

Objective： The aim of this study was to compare bone marrow-sparing intensity-modulated radiotherapy （IMRT） with IMRT without entering pelvic bone marrow as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods： For a cohort of 10 patients, bone marrow-sparing IMRT and routine IMRT planning were designed. The prescribed dose was 45 Gy/1.8 Gy/25f, 95% of the planning target volume received this dose. Doses were computed with a commercially available treatment planning system （TPS） using convolution/superimposition （CS） algorithm. Plans were compared according to dose-volume histogram （DVH） analysis in terms of planning target volume （PTV） homogeneity and conformity indices （HI and CI） as well as organs at risk （OARs） dose and volume parameters. Results： Bone marrow-sparing IMRT had an vantages over routine IMRT in terms of CI, but inferior to the latter for HI. Compared with routine IMRT, V5, Vl0, V20, V30, V40 of pelvic bone marrow of bone marrow-sparing IMRT reduced by 1.81%, 8.61%, 31.81%, 29.50%, 28.29%, respectively. No statistically significant differences were observed between bone marrow-sparing IMRT and routine IMRT in terms of small bowel, bladder and rectum. Conclusion： For patients with cervical cancer after hysterectomy, bone marrowsparing IMRT reduced the pelvic bone marrow volume irradiated at all dose levels and might be conducive to preventing the occurrence of acute bone marrow toxicity.

Clinical study of three dimensional conformal radiotherapy combined with intracavitary brachytherapy in the treatment of cervical cancer

Objective: The aim of our study was to evaluate the outcome and complications of cervical cancer patients undergoing conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT). Methods: Sixty cervical cancer patients were divided randomly into the conformal group and the conventional group. Thirty patients treated with 3D-conformal radiotherapy in the 3DCRT group, when the whole pelvic received DT 40 Gy, a planning CT scan of each patient was obtained and the second 3DCRT therapy plan was taken. Then, continued to irradiate to 50 Gy. At last, 3DCRT was boosted at local involved volumes to the total dose of 60 Gy. When 3DCRT was combined with intracavitary brachytherapy, the dose of brachytherapy to point A was 30 Gy/5 fractions. In the conventional group, after a total tumor dose of 40 Gy was delivered by the whole pelvic irradiation, the four-field technique was used to irradiate the total pelvic and regional nodes (median dose of 10 Gy), and the involved volumes were boosted to 60 Gy and the dose of brachytherapy to point A was 30 Gy-36 Gy/5-6 fractions. Moreover, both groups were combined with intracavitary brachytherapy respectively. Results: The 1, 2, 3-year survival rates for the 3DCRT group and the conventional group were 96.7%, 93.3%, 90.0% and 86.6%, 76.7%, 70% respectively (P = 0.04, P = 0.02 and P = 0.02). There was a statistically significant difference between the two groups. Compared to the two groups each other in toxic effects, except for the I-II grade rectal and bladder reaction and pelvic fibrosis which was lower in the 3DCRT group (P = 0. 007, P = 0. 006 and P = 0. 015), the side effects were similar and well tolerated in two groups. Conclusion: The all-course 3DCRT combined with intracavitary brachytherapy can be considered as an effective and feasible approach to cervical cancer and may significantly improve the survival rate and reduce the late toxicity. This new role for 3DCRT merits need further evaluation with large patient numbers and longer follows up.

Comparison of different treatment regimens for ⅠB2 and ⅡA2 cervical cancer

Objective： The aim of this study was to explore the difference of long-term prognosis of different treatment regimens in patients with stage IB2, IIA2 cervical Cancer. Methods： From August 1995 to September 2005, radical hysterectomy was chosen as primary treatment regimen for 122 patients （group A）, 85 patients underwent radical hysterectomy after ef- fective neoadjuvant therapy （group B）, and 98 patients received surgery after ineffective preoperative therapy （group C）. All patients received postoperative therapy. Results： Atotal of 305 patients were analyzed. The maximum diameter of tumor was largest in group B, while the pathological risk factors （cervical infiltration, positive surgical margins） were in the lowest propor- tion. The 5-year mortality rate and relapse rate of group B were the highest, and the overall survival （OS） and progression-free survival （PFS） were the shortest （P 〈 0.05）. No significant difference of long-term survival was found in group C and group A. No difference was found in the surgical of three groups. Large tumor more than 5.5 cm had higher effective ratio of treatment than those 5.5 cm or less. Patients received effective preoperative radiotherapy had better long-term prognosis than those received chemotherapy or radiochemotherapy. Conclusion： neoadjuvant treatment using for patients with IB2, IIA2 cervical cancer is effective in reducing risk factors of pathological, but it could not improve the long-term survival. The indications of adjuvant therapy after surgery should be reconsidered. Those tumors of diameter 5.5 cm or less response poor to neoadjuvant treatment, and no improvement of survival was found, so direct surgical treatment is suggested for these patients. Radiotherapy is a better choice of preoperative treatment.

Transfection with the ribozyme targeting HPVE6 mRNA results in growth inhibition of E6-expressing cervical carcinoma cells

Objective: To acquire a ribozyme against the E6 gene of human papillomaviruses type 16 (HPV16E6) and investigate its effects on the phenotypes and gene expression of cervical cancer cell line. Methods: Anti-HPV16E6 ribozyme (HRz) was designed by computer programs and its activity identified by cleavage experiment in vitro before its transfection via lipofectin into CaSKi cells with the empty eucaryotic expression plasmid transfection of the cells also performed, the resultant cells designated as CaSKi-R, CaSKi-P respectively. The morphology and the soft agar forming ability were studied in CaSKi cells and the transfected cells, and the expression of E6, proliferating cell nuclear antigen (PCNA) and C-erbB-2 genes assayed by flow cytometry. The tumorgenicity of each cell line was evaluated in nude mice receiving inoculations of CaSKi, CaSKi-R and CaSKi-P cells separately, while in one group, both CaSKi and CaSKi-R cells were inoculated on different sides of the mice. Results: HRz was able to cleave HPV16E6 mRNA in a site-specific manner and could be expressed stably in transfected CaSKi cells. Northern blot analysis showed that E6 mRNA was less in CaSKi-R than in CaSKi cells, and no significant difference in the morphology and growth rate was observed between CaSKi and CaSKi-P cells, but the growth rate CaSKi-R was lowered. The colony-forming rate of CaSKi-P in soft agar was similar to that of CaSKi cells, while that of CaSKi-R was decreased. Flow cytometry showed that anti-HPV16E6 ribozyme reduced the expression of E6, PCNA and C-erbB-2 genes in CaSKi-R cells, but not in CaSKi-P cells. The tumorgenicity of CaSKi-R in nude mice was decreased compared with CaSKi cells. Conclusion: HRz can partially reverse the malignant phenotype of CaSKi cells, possibly due to decreased E6 gene expression, and the consequent decrease of PCNA and C-erbB-2 gene expressions.

Clinical Report on Californium-252 Neutron Intraluminal Brachytherapy Combined with External Irradiation for Cervical Carcinoma Treatment

OBJECTIVE To observe the curative effects and complications of californium-252 （^252Cf） neutron intraluminal brachytherapy （IBT） combined with external irradiation （El） for treatment of cervical carcinoma.METHODS From December 2000 to December 2004, 128 cases of cer vical carcinoma staged into IIA-IIIB according to the International Federation of Gynecology and Obstetrics （FIGO） standards were treated with ^252Cf neutron IBT using 8-10 Gy per fraction, once a week. The total dose at reference A point was 36-40 Gy in 4-5 fractions. From the second day after ^252Cf neutron IBT treatment, the whole pelvic cavity was treated with ^60Co y-ray El, applying 2 Gy per fraction, 4 times per week. After 20-25Gy of El, the center of the whole pelvic field was blocked with 4 cm of lead in width. The total dose of El was 45-50 Gy.RESULTS The short-term therapeutic effects were CR 95.3% and PR 4.7%. The 3 and 5-year local control rates were 93.5% and 87.9%. The overall 3-year survival rate was 87.5% and for Stages Ⅱ and Ⅲ , 90.9% and 81.5% respectively; the overall 5-year survival rate was 70% and for Stages II and III, 76.2% and 61% respectively. The rate of radiation complications was 4.7% for radiation cystitis, 7.8% for radiation proctitis, 6.3% for vagina contracture and adhesion and 5.5% for protracted radiation proctitis.CONCLUSION An combination of ^252Cf neutron IBT with El for treatment of cervical carcinoma can be well-tolerated by cervical carcinoma patients. The rate of local tumor control is high and radiation complications are few.