Anatomical Morphology and Related Angles of Foramen Ovale: A Three-dimensional Computed Tomography Reconstruction.

This study aimed to report the three-dimensional reconstruction of the foramen ovale (FO) based on computed tomography angiography and describe its shape and related angles. A retrospective analysis of 199 adult patients who were hospitalised at the Department of Neurosurgery, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, China, from January to December 2020 was conducted. The original DICOM files of patients' computed tomography scans were processed by 3D Slicer software to reconstruct the three-dimensional skull. The morphological characteristics of the FO on both sides were analysed. Their size, related angles and volumes, and the differences between the two sides and gender were compared. A total of 398 FO from 199 patients were studied. The most frequent shape of the FO was oval, accounting for 54.27%. The mean lengths of the right and the left sides were 5.40±1.51 and 5.10±1.18mm, respectively. The mean width on the right and left sides was 3.23±1.16 and 3.33±1.19 mm, respectively. The FO is most commonly oval in shape. Clinicians may use the anatomical characteristics regarding the size and shape of the FO for diagnosis and treatment. Key Words: Foramen ovale, Computed tomographic angiography, 3-Dimensional anatomy.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.

Use of preoperative clinicopathologic characteristics to identify patients with low-risk cervical cancer suitable for Piver class II radical hysterectomy.

OBJECTIVE: To investigate the long-term efficacy of Piver-Rutledge class II radical hysterectomy (Piver II RH) for treatment of early-stage cervical cancer and to identify suitable candidates for this procedure. METHODS: A retrospective study was conducted of 432 cervical cancer patients (tumor size ≤4 cm) treated with Piver II RH at Sun Yat-sen University Cancer Center, Guangzhou, China, between January 1, 1999, and June 30, 2005. The correlation of preoperative and postoperative characteristics with recurrence and survival was analyzed. RESULTS: Median follow-up was 72 months; the overall recurrence rate was 14.6%. The 5-year recurrence-free survival (RFS) was 88.0% and the 5-year overall survival (OS) was 93.0%. Significant differences were observed between patients with small (≤2 cm) and large (>2 cm) tumors with regard to intra-pelvic recurrence (2.5% vs 13.4%; P=0.001), extra-pelvic recurrence (3.4% vs 9.9%; P=0.028), RFS (95.0% vs 86.0%; P=0.005), and OS (95.0% vs 87.0%; P=0.005). Preoperative tumor size was the only factor that correlated with recurrence (P=0.018), RFS (P=0.038), and OS (P=0.029) in a multivariate analysis. CONCLUSION: Cervical cancer patients with tumors of 2 cm or less were identified as candidates for Piver II RH, which promoted excellent local tumor control and long-term survival.

Clinical significance of peritumoral lymphatic vessel density and lymphatic vessel invasion detected by D2-40 immunostaining in FIGO Ib1-IIa squamous cell cervical cancer.

The clinical significance of lymphangiogenesis in cervical cancer remains controversial. Our aim was to investigate the correlation between lymphangiogenesis, lymphatic vessel invasion (LVI) and tumor metastasis, invasion and prognosis in squamous cell cervical cancer. Paraffin sections of 90 patients with FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) Ib1-IIa squamous cell cervical cancer were stained for immunohistochemistry with a D2-40 monoclonal antibody against the carcinoembryonic antigen M2A. The lymphatic vessel density (LVD) and LVI were measured, and their relationship with the clinicopathological data was analyzed. D2-40-positive lymphatic vessels were found in 75 of the 90 patients (83.3 %). All D2-40-positive vessels were located in peritumoral areas. The mean±SD of the peritumoral LVD was 10.08±4.16. The positive rate of LVI was 32.0 % (24/75). The recurrence rate of patients with LVD >10 (62.1 %, 18/29) was significantly higher than that of patients with LVD ≤10 (34.8 %, 16/46, P = 0.021). The 5-year recurrence-free survival rate of patients with LVD >10 (41.0 %) was significantly lower than that of patients with LVD ≤10 (67.0 %, P = 0.045). Univariate analysis showed that the peritumoral LVD (≤10 vs >10) was correlated with LVI (absent vs present, P = 0.016). The peritumoral LVD and LVI showed no correlation with age, FIGO stage, tumor size, tumor grade, depth of invasion, or pelvic lymph node metastasis (all: P > 0.05). Peritumoral lymphangiogenesis was correlated with the recurrence and recurrence-free survival in patients with squamous cell cervical cancer. Examination of peritumoral LVD in these patients might therefore help to estimate the risk of recurrence.

Clinical effects of irinotecan hydrochloride in combination with cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer.

OBJECTIVE: To evaluate the toxicity and efficacy of irinotecan plus cisplatin neoadjuvant chemotherapy (NACT) for cervical cancer. METHODS: A total of 120 cases with cervical cancer were divided into 2 groups and retrospectively reviewed: Sixty FIGO IB2-IIB patients in NACT group were treated with 2 cycles of irinotecan 60 mg/m(2) on days 1 and 8 plus cisplatin 60 mg/m(2) on day 1 followed by surgery. Sixty FIGO IB2-IIB patients in control group were treated directly with surgery. RESULTS: The 60 patients in NACT group received a total of 120 cycles. Grades III and IV neutropenia and diarrhea were seen in 15.8% and 11.7%, respectively, of all chemotherapy cycles. Six (10.0%) patients achieved complete remission, 33 (55.0%) achieved partial remission, 21 (35.0%) remained stable, and none had disease progression. Postoperatively the deep cervical stromal invasion and positivity of surgical margins were significantly fewer in the NACT group. The pelvic lymph node metastasis rate of responders to NACT was significantly lower than that of non-responders (12.8% vs 38.1%). With a median follow-up of 29 and 30 months, the intra-pelvic recurrence rate of the NACT group was significantly lower than that of the control group (3/60 vs 11/60, p=0.023), the 2-year recurrence-free survival and the 2-year overall survival was 82.3% and 86.1% in the NACT group, and 86.3%, 87.9% in the control group with no significant difference. Multivariate analysis showed that response to NACT was the only factor associated with survival (p=0.036). CONCLUSION: Irinotecan plus cisplatin NACT for cervical cancer has high efficacy and tolerable toxicity, and can significantly reduce the rates of deep cervical stromal invasion and positive surgical margins. Pelvic lymph node metastasis decreases significantly in responders compared with non-responders. The response to NACT can be considered as an independent prognostic factor.

Clinical significance of combined examination of pretreatment serum CYFRA21-1 and SCCAg in cervical cancer patients.

BACKGROUND AND OBJECTIVE: Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) can be used for the quantitative examination of fragment of cytokeratin 19, and is a valuable tumor marker in various malignancies. This study was to investigate the significance of pretreatment serum CYFRA21-1 and squamous cell carcinoma antigen (SCCAg) in diagnosis and their correlations to the clinicopathologic features of cervical carcinoma. METHODS: One hundred cervical carcinoma patients underwent pretreatment serum CYFRA21-1 and SCCAg evaluation; 20 healthy women were subjected as control. The specificity and sensitivity of CYFRA21-1 and SCCAg as diagnostic indexes were analyzed; their correlations to clinicopathologic features were investigated through univariate and multivariate analyses. RESULTS: The specificity of CYFRA21-1 and SCCAg in diagnosing cervical cancer were both 100%. The sensitivity of CYFRA21-1 and SCCAg in diagnosing cervical cancer were 36.0% and 47.0% respectively, without significant difference. The combined examination of CYFRA21-1 and SCCAg elevated the sensitivity to 60.0%, which was significantly higher than that of examining CYFRA21-1 alone. Univariate analysis showed elevation of CYFRA21-1 was related with FIGO stage and tumor size; elevation of SCCAg was related with pathologic type, tumor size, deep stromal invasion and pelvic node metastasis. Multivariate analysis showed that elevation of CYFRA21-1 had no relationship with any factors, while elevation of SCCAg was related with deep stromal invasion and pelvic node metastasis. The sensitivity of SCCAg in predicting pelvic node metastasis and deep stromal invasion were significantly higher than those of CYFRA21-1 (75.0% vs. 29.2%, p = 0.001; 55.8% vs. 26.9%, p = 0.024), and the addition of CYFRA21-1 to SCCAg could not significantly improve the sensitivity compared with SCCAg alone (79.2% vs. 75.0%, p > 0.05; 63.5% vs. 55.8%, p > 0.05). CONCLUSION: The value of pretreatment serum CYFRA21-1 as predictor of pelvic node metastasis and deep stromal invasion is less significant compared with that of SCCAg. For cervical squamous cell cancer, SCCAg is the preferred tumor marker.

[Analysis of recurrence pattern and prognosis of patients with cervical carcinoma and pelvic lymph node metastasis].

OBJECTIVE: To investigate the pattern of disease relapse and prognostic risk factor of patients with cervical carcinoma and pelvic lymph node metastasis. METHODS: A total of 124 cases of International Federation of Gynecology and Obstetrics (FIGO) Ib1-IIa cervical carcinoma with pelvic node metastasis who were treated at the Cancer Center of Sun Yat-sen University during January 1994 to December 2001 were selected for this study. Prognosis and recurrence were retrospectively analyzed using the clinico-pathological data RESULTS: The overall 5 year survival and 5 year disease-free survival were 63.3% and 61.4%, respectively. Overall recurrence rate was 39.5% (49/124), among which intra-pelvic relapse (61.0%, 25/41) was significantly more common than extra-pelvic relapse (31.7%,13/41; P=0.008). Multivariate analysis identified involvement of common iliac node as an independent prognostic factor (P=0.035). According to this factor, node-positive patients could be divided into low risk group (without common iliac node involvement, 104 cases) and high risk group (with common iliac node involvement, 20 cases). The 5 year disease-free survival were 69.4% and 24.5% respectively, with a significant difference (P=0.003). Intra-pelvic relapse was observed in 22.1% (23/104) of low risk and 25.0% (5/20) of high risk group respectively, with no significant difference (P>0.05). However extra-pelvic relapse was seen in 7.7% (8/104) of low risk and 40.0% (8/20) of high risk group, with a significant difference (P<0.01). CONCLUSIONS: Common iliac node involvement is a significant factor influencing the prognosis of patients with cervical carcinoma and pelvic lymph node metastasis. Patients with positive common iliac nodes have significantly decreased 5 year disease-free survival and higher extra-pelvic disease recurrence rates compared with those whose common iliac nodes are negative. These findings provide important data for design of individualized treatment mode.

Molecular diagnosis of sentinel lymph node metastases in cervical cancer using squamous cell carcinoma antigen.

PURPOSE: To clarify the prognostic value of molecular diagnosis of SLN metastases in cervical cancer using SCCA. EXPERIMENTAL DESIGN: All SLNs and primary tumors, part of non-SLNs, were harvested from 36 patients with cervical cancer. Expression levels of SCCA, cytokeratin 19 (CK19), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 178 samples (29 primary tumors, 5 histologic positive nodes, 60 histologic negative SLNs, 69 non-SLNs, and 15 normal nodes) were assessed by quantitative reverse transcription-PCR assay. The quantitative value of SCCA or CK19 mRNA was described as each value relative to GAPDH mRNA. The cutoff value was set at the upper limit of the quantitative value of nodes from noncancer patients, and those above this value constituted the molecular metastasis group. RESULTS: The SCCA mRNA expression values were more than 1 x 10(3) in 28 primary tumors and all histologic positive nodes, and its expression levels in SLNs were higher than in non-SLNs. SLNs from patients with adverse prognostic features had higher SCCA mRNA expression levels. Four histologic negative SLNs were diagnosed molecular metastases based on SCCA mRNA. Two cases with histologically uninvolved pelvic nodes recurred. Survival analysis indicates that molecular lymphatic metastasis based on elevated SCCA mRNA level is the best predictor of recurrence. However, CK19 is not a suitable marker due to its low specificity and relative higher baseline expression in normal nodes. CONCLUSIONS: SCCA mRNA levels for molecular diagnosis of SLN metastases in cervical cancer more accurately identifies patients at risk for recurrence than the routine histology does.

[Expression and clinical significance of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 in epithelial ovarian cancer].

BACKGROUND & OBJECTIVE: Some studies have showed that changes of autophagic capacity may be correlated to tumorigenesis and tumor development. This study was to investigate the expression of microtubule-associated protein 1 light chain 3 (LC3) and autophagy-related gene Beclin1 in ovarian tumor tissues, and explore their correlations to the tumorigenesis and development of epithelial ovarian carcinoma. METHODS: Expressions of LC3 and Beclin1 in 25 specimens of benign ovarian tumor, 25 specimens of borderline ovarian tumor, and 75 specimens of epithelial ovarian carcinoma were detected by immunohistochemistry. The correlations of LC3 and Beclin1 expression to the clinicopathologic characteristics of the 75 epithelial ovarian cancer patients were analyzed. RESULTS: The positive rates of LC3 and Beclin1 were significantly higher in benign and borderline ovarian tumors than in epithelial ovarian carcinoma (100% and 96% vs. 57%, P<0.001; 100% and 84% vs. 57%, P<0.001). The expression of LC3 was associated with FIGO stage and histological grade (P=0.017;0.001). The expression of Beclin1 was related to FIGO stage (P=0.04). The expression of LC3 was not correlated to Beclin1 (P=0.875). CONCLUSIONS: Expressions of LC3 and Beclin1 are down-regulated in epithelial ovarian cancer tissues. The decrease of autophagic capacity may relate to tumorigenesis and the development of epithelial ovarian cancer.

Sentinel lymph node detection using methylene blue in patients with early stage cervical cancer.

OBJECTIVE: To evaluate the feasibility of sentinel lymph node (SLN) detection in patients with cervical cancer using the low-cost methylene blue dye and to optimize the application procedure. PATIENTS AND METHODS: Patients with stage Ib(1)-IIa cervical cancer and subjected to abdominal radical abdominal hysterectomy and pelvic lymphadenectomy were enrolled. Methylene blue, 2-4 ml, was injected into the cervical peritumoral area in 77 cases (4 ml patent blue in the other four cases) 10-360 min before the incision, and surgically removed lymph nodes were examined for the blue lymph nodes that were considered as SLNs. RESULTS: High SLN detection rate was successfully achieved when 4 ml of methylene blue was applied (93.9%, 46/49). Bilaterally SLN detection rate was significantly higher (78.1% vs. 47.1% P=0.027) in cases when the timing of application was more than 60 min before surgery than those with timing no more than 30 min. The blue color of methylene blue-stained SLNs sustained both in vivo and ex vivo, compared with the gradually faded blue color of patent blue that detected in 3 of 4 cases unilaterally. In the total of 112 dissected sides, the most common location of SLNs was the obturator basin (65.2%, 73/112), followed by external iliac area (30.4%, 34/112) and internal iliac area (26.8%, 30/112). Three patients who gave false negative results all had enlarged nodes. CONCLUSION: Methylene blue is an effective tracer to detect SLNs in patients with early stage cervical cancer. The ideal dose and timing of methylene blue application are 4 ml and 60-90 min prior surgery, respectively.

[Correlation of serum squamous cell carcinoma antigen with clinico-pathological features and prognosis of squamous cell carcinoma of uterine cervix].

OBJECTIVE: To investigate the correlation of pretreatment serum squamous cell carcinoma antigen (SCCAg) with the clinico-pathological features of squamous cell carcinoma of uterine cervix and its significance as a prognostic factor. METHODS: One hundred and fourteen patients of squamous cell carcinoma of the uterine cervix (Ib1-IIa), who underwent pretreatment serum SCCAg evaluation and long-term follow-up after treatment were selected for this study. Clinical data were used to investigate the correlation between SCCAg and clinico-pathological features and factors that influence prognosis through univariate and multivariate analysis. RESULTS: Univariate analysis showed elevation of SCCAg (using < or = 1.5 mg/L as the cut-off value) was correlated with tumor size, deep stromal invasion and pelvic node metastasis (P < 0.05). Multivariate analysis revealed significant correlations between elevation of SCCAg and deep stromal invasion (P = 0.029) and pelvic node metastasis (P = 0.049). The 5 years disease-free survival (DFS) was 78.6%, and recurrence rate was 27.2%. Univariate analysis revealed that elevated pretreatment SCCAg and pelvic node metastasis were significantly correlated with DFS and recurrence (P < 0.05). Multivariate analysis identified elevated pretreatment SCCAg (P = 0.030), pelvic node metastasis (P = 0.003) as independent prognostic factors, and pelvic node metastasis (P = 0.006) as a factor significantly correlated with recurrence after treatment. Comparison between pelvic node metastasis + elevated SCCAg cases and pelvic node metastasis + normal SCCAg cases showed no significant difference in DFS (50.9% vs 50.0%), recurrence rate (47.1% vs 60.0%), local recurrence (20.0% vs 3/8) and distant recurrence (20.0% vs 1/8; all P > 0.05). However, between no pelvic node metastasis + elevated SCCAg cases and no pelvic node metastasis + normal SCCAg cases, there was a significant difference in DFS (71.8% vs 98.0%, P = 0.003), recurrence rate (33.3% vs 9.8%, P = 0.006) and local recurrence (26.5% vs 2.1%, P = 0.001). CONCLUSIONS: The independent prognostic factors for Ib1-IIa squamous cell carcinoma of uterine cervix include elevated pretreatment SCCAg and pelvic node metastasis. Patients with elevated pretreatment serum SCCAg and no metastasis to pelvic lymph node (s) are at significantly elevated risk of local recurrence, and therefore need individualized treatment to improve local control and long-term survival.

[Correlation of CXCR4/CXCL12 overexpression to lymph node metastasis and chronic inflammation in cervical adenocarcinoma].

BACKGROUND & OBJECTIVE: CXCL12 is a kind of chemokine. CXCR4, the specific receptor of CXCL12, is involved in metastasis of tumors. CXCR4/CXCL12 expression in cervical adenocarcinoma has seldom been reported. This study was to investigate the correlation of CXCR4/CXCL12 overexpression to lymph node metastasis and chronic inflammation in cervical adenocarcinoma. METHODS: CXCR4 and CXCL12 immunohistochemical staining and HE staining were performed in 35 specimens of cervical adenocarcinoma, including 8 with lymph node metastasis and 27 without. Marked expression of CXCR4 or CXCL12 observed in more than 90% tumor cells was defined as overexpression. Fisher's exact test, Chi-square test, and Pearson correlation test were used to analyze the results. RESULTS: All 35 specimens of cervical adenocarcinoma expressed CXCR4. The overexpression rate of CXCR4 was significantly higher in the cases with lymph node metastasis than in those without (62.50% vs. 22.00%, P<0.05), slightly higher in the IB cases with lymph node metastasis than in those without (33.33% vs. 26.01%, P>0.05), and significantly higher in the IIB cases with lymph node metastasis than in those without (80.00% vs. 0.00%, P<0.05). The positive predictive value of CXCR4 overexpression to assess lymph node metastasis was 45.45%, and the negative predictive value was 87.50%. A variable number of tumor cells in 33 specimens expressed CXCL12. The overexpression rate of CXCL12 was significantly higher in IB cases than in IIB cases either in tumors with lymph node metastasis (0.00% vs. 80.00%, P<0.05) or without (21.73% vs. 75.00%, P<0.05). CXCR4 overexpression was positively correlated to CXCL12 overexpression in the 23 IB cases without lymph node metastasis; but the correlation did not exist in the 3 IB cases with lymph node metastasis and the 9 IIB cases. All the 35 specimens were accompanied with chronic inflammation; the infiltrates were mainly lymphocytes. CXCL12 overexpression was not correlated to the infiltration degree of chronic inflammation. CONCLUSIONS: CXCR4 overexpression indicates a higher lymph node metastasis potential of cervical adenocarcinoma. The overexpression rate of CXCL12 is increasing by the progression of tumors. The chronic inflammatory cells in cervical adenocarcinoma are not attracted by CXCL12.

[Effect of survivin shRNA on chemosensitivity of human ovarian cancer cell line OVCAR3 to paclitaxel].

BACKGROUND & OBJECTIVE: Drug resistance is a major obstacle to the successful chemotherapy of ovarian cancer. Recent studies have shown overexpression of Survivin in ovarian cancer tissues and cell lines, which may play an important role in the drug resistance of ovarian cancer. This study was to explore the effects of Survivin short hairpin RNA (shRNA) on Survivin expression, apoptosis, and chemosensitivity of human ovarian cancer cell line OVCAR3. METHODS: OVCAR3 cells were transfected with Survivin shRNA. Untransfected, lip-transfected, and mU6-transfected cells were set as controls. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of Survivin mRNA. Flow cytometry was applied to examine the expression of Survivin protein and cell apoptosis. MTT assay was used to examine the effect of Survivin shRNA on chemosensitivity of OVCAR3 cells. RESULTS: The mRNA and protein levels of Survivin were obviously lower in Survivin shRNA-transfected OVCAR3 cells than in untransfected cells, lip-transfected cells, and mU6-transfected cells 24 h after transfection. The apoptotic rates of OVCAR3 cells 12 h, 24 h, 36 h, 48 h after Survivin shRNA transfection were 20.7%, 31.9%, 39.0%, and 46.7%, respectively, that showed a time-dependent manner. The 50% inhibitory concentrations (IC50) of paclitaxel were (0.305+/-0.032) micromol/L for untransfected cells, (0.157+/-0.031) micromol/L for lip-transfected cells, (0.175+/-0.010) micromol/L for mU6-transfected cells, and (0.019+/-0.001) micromol/L for Survivin shRNA-transfected cells; and the IC50 of cisplatin were (9.410+/-0.796) micromol/L, (6.675+/-1.739) micromol/L, (6.930+/-1.273) micromol/L, and (7.862+/-0.081) micromol/L, respectively. Survivin shRNA increased the sensitivity of OVCAR3 cells to paclitaxel by 16 folds (P<0.01), but had no significant effect on the sensitivity to cisplatin (P>0.05). CONCLUSION: Sequence-specific shRNA targeting Survivin can suppress the expression of Survivin gene effectively in OVCAR3 cells, and sensitize OVCAR3 cells to paclitaxel, but has no significant effect on the sensitivity to cisplatin.

[Influence of short hairpin RNA on survivin mRNA expression and chemosensitivity to paclitaxel in ovarian cancer cells].

OBJECTIVE: To investigate the influence of short hairpin RNA (shRNA) expression plasmid against gene survivin (mU(6)/survivin) on survivin mRNA expression and chemosensitivity to paclitaxel in ovarian cancer cells OVCAR3. METHODS: OVCAR3 cells were transfected with plasmid pEGFPC(2) formulated with lipofectamine 2000 at different concentrations. The transfection efficiency was examined by flow cytometry. The expression of survivin mRNA of OVCAR3 cells after transfection with the plasmid mU(6)/survivin with the high efficiency ratio was observed by RT-PCR. The effect of the plasmid on the cell cycle and apoptosis was analyzed by flow cytometry. The chemosensitivities of transfected cells to paclitaxel were determined by methyl thiazolyl tetrazolium (MTT). RESULTS: The optimal transfection efficiency was obtained when pEGFPC(2): lipofectamine 2000 was 1: 2. Compared with the non-transfected groups, 0.81 +/- 0.05, the mRNA of survivin in OVCAR3 cells was reduced clearly after transfection with mU(6)/survivin, 0.26 +/- 0.04. shRNA reduced the expression level of survivin mRNA to 32% of non-transfected groups (P < 0.01). The apoptotic rate of survivin shRNA group reached (31.9 +/- 1.2)%, which was much higher than those of non-transfected (4.9 +/- 0.7)% and lip alone groups (5.6 +/- 0.5)% (P = 0.000). Cell cycle analysis showed that survivin shRNA induced accumulation of cells in G(0)/G(1) phase with a decrease of cells in G(2)/M phase after being cultured for 24 hours compared with non-transfected group (P < 0.01). MTT results showed that the 50% inhibiting concentration (IC(50)) of paclitaxel in non-transfected, lip alone and survivin shRNA transfected groups was (0.305 +/- 0.032), (0.157 +/- 0.031), and (0.019 +/- 0.001) micromol/L respectively. Compared with non-transfected group, shRNA increased the chemosensitivity of OVCAR3 cells to paclitaxel by 16 fold (P = 0.000). CONCLUSION: Sequence specific shRNA targeting survivin can effectively suppress the expression of survivin mRNA and enhance the chemosensitivity to paclitaxel in ovarian cancer cells significantly.

[Recurrence risk factors of platinum-sensitive epithelial ovarian cancer].

BACKGROUND & OBJECTIVE: The prognosis of platinum-sensitive ovarian cancer patients was better than that of chemoresistant ones. However, platinum-sensitive ovarian cancer patients still have a high recurrence rate, which affects their prognosis. This study was designed to analyze clinical features and recurrence risk factors of platinum-sensitive epithelial ovarian cancer. METHODS: Factors that might relate to recurrence of 90 platinum-sensitive epithelial ovarian cancer patients, admitted in Cancer Center of Sun Yat-sen University from 1993 to 1999, with complete remission of more than 6 months, were assessed. Univariate analysis was performed using Chi(2) test; while multivariate analysis was carried out using Cox proportional hazard model. RESULTS: Among the 90 patients, 36(40.0%) relapsed with the median recurrence-free interval of 20 months. Pelvic cavity (18/36, 50.0%) was the most frequently involved. The 3-and 5-year survival rates of all patients were 79.6% and 69.5%; while those of the recurrent ones were 62.3% and 39.6%. Univariate analysis showed that the early FIGO stage group, mucinous type group, and no neoadjuvant chemotherapy group had lower recurrence rates than advanced FIGO stage group, non-mucinous type group, and neoadjuvant chemotherapy group, respectively (P=0.001, P=0.002, and P=0.025). Cox multivariate analysis showed that only FIGO stage was the independent risk factor of recurrence of ovarian cancer (risk ratio=1.771, P=0.003). There was no significant difference in recurrence rate between CBP and other postoperative chemotherapy regimen groups. More cycles of chemotherapy could not reduce the recurrence rate. CONCLUSION: Since FIGO stage is an independent recurrence risk factor of platinum-sensitive epithelial ovarian cancer patients, early diagnosis is the key point to decrease the recurrence rate.

[Expression of metastasis suppressor gene KAI1/CD82 in cervical squamous cell carcinoma and its clinical significance].

BACKGROUND & OBJECTIVE: Metastasis suppressor gene KAI1/CD82 plays an important role in infiltration and metastasis of several types of human cancers, while the researches on its relation with cervical carcinoma are far from adequate now. Therefore, immunohistochemical techniques were employed in this study to determine the expression of KAI1 gene, and explore its clinical significance in cervical squamous cell carcinoma. METHODS: SP immunohistochemistry was used to detect the expression of KAI1 gene in 99 specimens of cervical squamous cell carcinoma, 25 specimens of cervical intraepithelial neoplasm (CIN) II-III, and 18 specimens of normal cervix. Correlations of expression of KAI1 gene to clinicopathologic factors, and prognosis of cervical squamous cell carcinoma were statistically analyzed. RESULTS: The rates of negative, weak, moderate, and strong expression of KAI1 in cervical squamous cell carcinoma were 52.5% (52/99), 16.2% (16/99), 15.2% (15/99), and 16.2% (16/99), respectively, significantly lower than those in normal cervix, and CIN II-III (P=0.000). Expression of KAI1 has no correlation with FIGO stage, age, pelvic lymph node metastasis, tumor histological grade, depth of cervical infiltration, serum squamous cell carcinoma antigen (SCC) level, tumor size, and gross type of cervical lesion (P>0.05). Both univariate and multivariate analyses showed expression of KAI1 has no correlation with prognosis of cervical squamous cell carcinoma (P>0.05). CONCLUSION: KAI1 gene may be an early event in development of cervical cancer, and has no correlation with prognosis of cervical squamous cell carcinoma.

Up-regulated expression of cytoplasmic clusterin in human ovarian carcinoma.

BACKGROUND: Recently, tumorigenic roles of the clusterin gene in several human malignancies have been suggested, but its potential role in the development and progression of ovarian carcinoma is unclear. METHODS: In the current study, immunohistochemistry was used to examine the expression status of clusterin in 10 normal ovaries, 20 ovarian cystadenomas, 15 borderline ovarian tumors, and 240 ovarian carcinomas (nonmetastatic and metastatic) by tissue microarray. In addition, the apoptotic index of each tumor was assessed with a terminal deoxyuridine triphosphate nick-end labeling assay. RESULTS: Positive staining for clusterin in different ovarian tissues was observed primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal ovaries, in 17% of cystadenomas, in 38% of borderline tumors, and in 58% of invasive ovarian carcinomas. A significant association was observed (P < 0.001) between the overexpression of clusterin and late clinical stage according to the International Federation of Gynecology and Obstetrics staging system. In addition, the overexpression of clusterin was detected more frequently in metastatic lesions than that in their matched primary tumors. The current results also provided evidence that the overexpression of cytoplasmic clusterin in carcinomas was correlated inversely with the tumors' apoptotic index, demonstrating an antiapoptotic function of cytoplasmic clusterin in ovarian carcinomas. CONCLUSIONS: The current results suggested that the overexpression of cytoplasmic clusterin may represent an acquired malignant phenotypic feature of ovarian carcinoma and may be one of the important factors in determining the aggressive nature of ovarian carcinoma.

[Comparison of pelvic transarterial chemoembolization with lipiodol ultra-fluid carboplatin and transarterial carboplatin through experiment in dogs].

BACKGROUND & OBJECTIVE: Transarterial chemoembolization, based on transarterial chemotherapy, is a new treatment for malignant neoplasms. This study was to investigate distribution of platinum (Pt) in blood and uterine tissue after infusing different carboplatin arterially. METHODS: Fourteen female dogs were randomly divided into 2 groups: embolizational group (group A, 7 dogs),and chemotherapy group (group B, 7 dogs). In group A, carboplatin (12 mg/kg), mingled with lipidol ultra-fluid (0.2 ml/kg), was injected into dogs' iliac arteries. In group B, carboplatin (12 mg/kg), dissolved in 5% glucose, was injected into the same arteries. The uterine tissues and blood samples were collected at different time points, concentrations of Pt in samples were measured by atomic absorption method. RESULTS: Peak concentration of Pt in uterine tissues of group A was (215.0+/-17.6) microg/g, that of group B was (211.3+/-40.1) microg/g (P >0.05), the peak appeared at 0 min in both groups. Area under concentration-time curve (AUC) of Pt in tissues of group A was (13.9+/-3.9) mg x min x g(-1), significantly larger than that of group B (5.9+/-0.6) mg x min x g(-1). Peak concentration of Pt in plasma of group A was (8.7+/-12.5) microg/g, that of group B was (16.7+/-3.6) microg/g. AUC(0-240 min) was (0.5+/-0.1) mg x min x g(-1) in group A,and (1.2+/-0.4) mg x min x g(-1) in group B (P< 0.05). CONCLUSION: Compared with arterial chemotherapy, arterial chemo- embolization may result in higher Pt concentration in local area, and lower Pt concentration in plasma, it may reduce the systemic toxicities, and enhance local effect on tumor.

[Sentinel lymph node identification with methylene blue in cervical cancer].

BACKGROUND & OBJECTIVE: Study of sentinel lymph node(SLN) in cervical cancer has been initiated since recent years, and there are still a lot of unknown factors about SLN identification in cervical cancer. This study was to investigate influential factors of identifying SLN with methylene blue in cervical cancer. METHODS: For 41 patients with cervical cancer enrolled from Jun. 2002 to May 2003, 2-4 ml of methylene blue was injected into cervix at 4-6 sites around the tumor about 90-400 min before operation. The blue-dyed lymph node (BDLN) was considered as SLN. HE staining in step sections, and immunohistochemistry were applied to detect SLN. The influential factors of using methylene blue to detect SLN in cervical cancer were assessed based on the identification rate of SLN, and its false negative rate. RESULTS: SLNs were detected in 31 of 41(75.6%) patients with cervical cancer of stage Ib1-IIb. A total of 85 SLNs were identified,and most frequently located in obturator fossa. SLNs were successfully detected in 20 of 23 (87.0%) patients who had no preoperative radiotherapy or chemotherapy, while in only 11 of 18 (61.1%) patients who had preoperative radiotherapy and/or chemotherapy. SLNs were detected in only 17 of 27(63.0%) patients who were injected with 2-3 ml of methylene blue, while in all of 14 patients whose dose was 3.4-4 ml. Eight patients were confirmed of lymph node metastases by pathology. CONCLUSIONS: The dose of methylene blue recommended to detect SLN in cervical cancer is 3-4 ml. SLN varies in different sites, but most frequently located in obturator fossa.

[Clinical analysis of 8 cases of vulvar Paget's disease].

BACKGROUND & OBJECTIVE: Vulvar Paget's disease is a rare disease. It has a relatively high misdiagnosis rate and there are still controversies regarding its treatment. The objective of this study was to investigate its clinical features and summarize the experience of the management of this disease in order to gain a better acknowledge of this rare disease and improve its cure rate. METHODS: The clinical records of 8 cases of vulvar Paget's disease admitted in Cancer Center, Sun Yet-sen University from January 1964 to December 2001 were analyzed. RESULTS: The average age of 8 cases was 66.5 years, and the mean time from the onset of the disease to diagnosis was 5 years. Pathologically, intraepithelial Paget's disease was the commonest (5/8), followed by invasive Paget's disease (2/8) and Paget's disease with underlying adenocarcinoma (1/8). Eight cases underwent altogether 10 times of surgery, and radical vulvectomy was the most frequently used procedure (6/10). One case of Paget's disease with underlying adenocarcinoma died 21 months after surgery and 1 case of intraepithelial Paget's disease died of other etiology, 5 cases achieved long-term disease free survival, 1 case developed recurrence. CONCLUSION: Surgery is the first choice for the patients of vulvar Paget's disease. For those patients whose lesions are extensive,or old aged,or not suitable for long-term follow-up, a radical vulvectomy is more preferable and a lower recurrence rate is expected.