A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors.

Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination (HR) deficiency. However, many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin. The biomarker responsible for this mechanism remains unclear. Here, we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients. PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage (ATM) signaling-induced pro-apoptotic ribosomal stress, which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage. Therefore, the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin. The gene panel as an independent biomarker was validated by multiple published clinical datasets, as well as by an ovarian cancer organoids library we established. More importantly, its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data. Furthermore, we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines. These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance. Together, our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.

Obtaining Greatly Improved Dielectric Constant in BaTiO3-Epoxy Composites with Low Ceramic Volume Fraction by Enhancing the Connectivity of Ceramic Phase.

Ceramic-polymer dielectric composites show promising potential as embedded capacitors, whereas it is a great challenge to obtain a high dielectric constant (εr) at a low ceramic volume fraction (Vc). This work demonstrates a strategy for overcoming this challange. By employing a high sintering temperature (Ts) and introducing porogen, BaTiO3 ceramics with both great connectivity and high porosity are obtained, and the composites with improved εr at a low Vc are prepared after curing the epoxy monomer, which is infiltrated into the porous ceramic bodies. For the composite with a Ts of 1300 °C and a Vc of 38.1%, the εr is as high as 466.8 at 1 kHz, which is improved by about nine times compared to the 0-3 counterpart with a higher Vc of 60.8%. Furthermore, the composite exhibits low dielectric loss and good frequency and temperature stability of εr, indicating the great potential for practical applications. Finite element simulation shows that the enhanced connectivity of BaTiO3 increases the electric field intensity in high-εr BaTiO3 dramatically and therefore plays a key role in the dielectric response of the composite. This work not only sheds light on the high-εr ceramic-polymer composites but also deepens the understanding on the relationship between their properties and microstructures.

Management of pelvic organ prolapse of ruptured and extruded bladder from a rare complication of vaginal hysterectomy: a case presentation.

BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

Survivin Promotes Piperlongumine Resistance in Ovarian Cancer.

Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway in vitro, while exerting a remarkable inhibitory influence on the proliferation of ovarian cancer cells. Overexpression of survivin raises the survival rate of ovarian cancer cells to PL. Moreover, PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin in vivo. Our findings reveal a previously unrecognized mechanism of PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer and suggest that ROS-mediated proteasome-dependent pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin.

Celastrol Inhibits the Growth of Ovarian Cancer Cells in vitro and in vivo.

Celastrol is a natural triterpene isolated from the Chinese plant Thunder God Vine with potent antitumor activity. However, the effect of celastrol on the growth of ovarian cancer cells in vitro and in vivo is still unclear. In this study, we found that celastrol induced cell growth inhibition, cell cycle arrest in G2/M phase and apoptosis with the increased intracellular reactive oxygen species (ROS) accumulation in ovarian cancer cells. Pretreatment with ROS scavenger N-acetyl-cysteine totally blocked the apoptosis induced by celastrol. Additionally, celastrol inhibited the growth of ovarian cancer xenografts in nude mice. Altogether, these findings suggest celastrol is a potential therapeutic agent for treating ovarian cancer.

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer.

Overexpression of drug efflux transport ABCB1 is correlated with multidrug resistance (MDR) among cancer cells. Upregulation of ABCB1 accounts for the recurrence of resistance to docetaxel therapy in ovarian cancer with poor survival. Erastin is a novel and specific small molecule that targets SLC7A11 to induce ferroptosis. In the present research, we explored the synergistic effect of erastin and docetaxel in ovarian cancer. We confirmed that the co-delivery of erastin with docetaxel significantly decreased cell viability, promoted cell apoptosis, and induced cell cycle arrest at G2/M in ovarian cancer cells with ABCB1 overexpression. Mechanistically, erastin dominantly elevated the intracellular ABCB1 substrate levels by restricting the drug-efflux activity of ABCB1 without alteration of the expression of ABCB1. Consequently, erastin can reverse ABCB1-mediated docetaxel resistance in ovarian cancer, revealing that the combination of erastin and docetaxel may potentially offer an effective administration for chemo-resistant patients suffering from ovarian cancers.

YM155 enhances docetaxel efficacy in ovarian cancer.

YM155 (Sepantronium bromide) is a potent small molecule inhibitor of survivin by suppression of survivin expression and shows the promising anticancer activity in many types of cancers. Docetaxel (Taxotere®) is a member of the taxane drugs used in the treatment of a number of cancers in clinic. Despite the therapeutic efficacy of docetaxel is encouraging, the emergent resistance is an urgent issue. In this study, we investigate the effect of YM155 on docetaxel efficacy in ovarian cancer cells. Our data showed that YM155 actively induced cell growth inhibition, cell cycle arrest and apoptosis with downregualtion of survivin in ovarian cancer cells. Moreover, YM155 increased the intracellular ROS levels, and pretreatment with either NAC or GSH partially reversed the YM155-induced ROS accumulation and apoptosis only in the parental A2780 cells, but not in the resistant A2780/Taxol cells. Furthermore, YM155 enhanced docetaxel efficacy to inhibit the growth and induce apoptosis in ovarian cancer cells. Take together, our results suggested that combination of YM155 and docetaxel may be a feasible strategy for the treatment of ovarian cancer.

Crizotinib synergizes with cisplatin in preclinical models of ovarian cancer.

Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells. Crizotinib also increases the intracellular reactive oxidative species (ROS) levels, and pretreating with ROS scavenger N-acety-L-cysteine partially reverses crizotinib-induced apoptosis. Moreover, crizotinib can synergistically inhibit ovarian cancer cells growth in vitro and in vivo when combines with cisplatin. Altogether, crizotinib potently potentiates the activity of cisplatin in ovarian cancer, suggesting the synergistic effect of crizotinib and cisplatin may be valuable for ovarian cancer patients' treatment.

Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer.

Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic outcome currently is unsatisfied. Dinaciclib, a novel small molecule inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the treatment of several types of cancers. In this study, we investigated the anticancer effects and mechanisms of dinaciclib alone or combined with cisplatin in ovarian cancer. Dinaciclib alone actively induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular ROS levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins, Mcl-1, XIAP and survivin. Pretreatment with N-acety-L-cysteine significantly blocked ROS generation but only partially rescued apoptosis triggered by dinaciclib. Moreover, the combination of dinaciclib with cisplatin synergistically promoted cell cycle arrest and apoptosis, and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Altogether, dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer, indicating this beneficial combinational therapy may be a promising strategy for treatment of ovarian cancer.

Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer.

Volasertib (BI 6727), a highly selective and potent inhibitor of PLK1, has shown broad antitumor activities in the preclinical and clinical studies for the treatment of several types of cancers. However, the anticancer effect of volasertib on cervical cancer cells is still unknown. In the present study, we show that volasertib can markedly induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreased protein expressions of PLK1 substrates survivin and wee1 in human cervical cancer cells. Furthermore, volasertib also enhances the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine totally blocks ROS generation but partly reverses volasertib-induced apoptosis. In addition, volasertib significantly potentiates the activity of cisplatin to inhibit the growth of cervical cancer in vitro and in vivo. In brief, volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer, suggesting the combination of volasertib and cisplatin may be a promising strategy for the treatment of patients with cervical cancer.

Piperlongumine induces apoptosis and synergizes with cisplatin or paclitaxel in human ovarian cancer cells.

Piperlongumine (PL), a natural alkaloid from Piper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.

Triterpenoids as reversal agents for anticancer drug resistance treatment.

Overexpression of ATP-binding cassette (ABC) transporters in cancer cells results in multidrug resistance (MDR), which is one of the major obstacles in the treatment of cancer patients. None of the strategies to overcome MDR has been successfully applied in the clinic until now. Plenty of evidence shows that some triterpenoids function as reversal agents of MDR for anticancer drug resistance treatment. Here, we review the latest findings of reversing cancer MDR with triterpenoids. Findings are summarized showing that triterpenoids are MDR modulators and potential chemosensitizers. Finally, we contemplate future prospects of modulating MDR in the clinic.

Recombinant bactericidal/permeability-increasing protein inhibits endotoxin-induced high-mobility group box 1 protein gene expression in sepsis.

We investigated in vivo the effect of recombinant bactericidal/permeability-increasing protein (rBPI21) on high-mobility group box 1 protein (HMGB1) expression in sepsis and its potential mechanism. Using a sepsis model induced by cecal ligation and puncture (CLP), rats were randomly divided into four groups as follows: normal control group, sham-operated group, CLP group, and BPI treatment group. Animals were killed at designated time points, and blood and tissue samples from liver, lungs, kidneys, and small intestine were harvested to determine related variables. In addition, we observed the effect of treatment with rBPI21 on survival rate in septic rats. The results showed that endotoxin content and expression levels of HMGB1 and LPS binding protein/CD14 mRNA in various organs were significantly increased at 12 and 24 h after CLP, which can be attenuated by treatment with rBPI21 (P<0.05-0.01). Meanwhile, treatment with rBPI21 in septic rats can markedly reduce serum alanine aminotransferase, creatinine levels, and pulmonary myeloperoxidase activity at 12 and 24 h after CLP, increase diamine oxidase activity at both time points (P<0.05-0.01), and improve the 1- to 10-day survival rates in animals subjected to CLP (P=0.012). These findings suggest that treatment with rBPI21 can significantly reduce endotoxin contents and expression levels of HMGB1 and LPS binding protein/CD14 mRNA in various organs in sepsis induced by CLP, and can protect against multiple organ damage resulting from sepsis. The effect of rBPI21 inhibiting HMGB1 gene expression in sepsis might be associated with endotoxin-dependent mechanisms.

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.

Sodium butyrate prevents lethality of severe sepsis in rats.

This study was performed to investigate a novel strategy to pharmacologically inhibit high-mobility group box 1 protein (HMGB1) expression with sodium butyrate, a short-chain fatty acid. Using a sepsis model induced by cecal ligation and puncture (CLP), 100 male Wistar rats were randomly divided into 4 groups as follows: control group (10 rats), sham operation group (10 rats), CLP group (further randomized into 2, 6, 12, 24, 48, and 72 h post-CLP subgroups, each 10 rats), and sodium butyrate treatment group (further randomized into 12 and 24 h post-CLP subgroups, each 10 rats). Animals of all groups were killed at designated time points, and blood and tissue samples from livers, lungs, kidneys, and small intestines were harvested to determine organ damage-related variables, and HMGB1 mRNA expression was assessed by the reverse-transcription-polymerase chain reaction. In addition, we observed the effect of treatment with sodium butyrate on survival rate in septic rats. The results showed that early treatment with sodium butyrate can markedly reduce serum alanine aminotransferase, creatinine levels at 12 h, and pulmonary myeloperoxidase activity at 24 h post-CLP, and significantly improve the 1- to 6-day survival rates in animals subjected to CLP (P < 0.05-0.01). These findings suggest that HMGB1 is excessively expressed and produced in sepsis. Sodium butyrate can markedly inhibit HMGB1 mRNA expression and may have protective effect on multiple organ damage in sepsis.

[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.

[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.