Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.

Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.

Predictive factors for residual disease in hysterectomy specimens after conization in early-stage cervical cancer.

OBJECTIVE: To identify predictive factors for residual disease in hysterectomy specimens after a loop electrical excision procedure (LEEP) or cold knife conization in early-stage cervical cancer. STUDY DESIGN: A retrospective review was undertaken of the clinical records and pathology reports of 108 consecutive patients who were diagnosed with early invasive cervical cancer stage IA1 to IB1 by cold knife conization or LEEP, and underwent subsequent hysterectomy or radical hysterectomy at the Gynae-oncology Unit, Queen Elizabeth Hospital between 2000 and 2012. Residual disease was defined as the presence of cervical intra-epithelial neoplasia (CIN) 2-3 or invasive carcinoma in hysterectomy specimens. Clinicopathological factors associated with residual disease were analyzed. Risk factors for the prediction of residual disease were identified by univariate and multivariate analysis. RESULTS: Residual disease was found in 32 (29.7%) patients. Stage, tumour size, depth of invasion, lymphovascular space invasion, ectocervical margin, endocervical margin, and combined ectocervical and endocervical margin were significantly associated with residual disease in hysterectomy specimens on univariate analysis. On multivariate analysis, depth of invasion (odds ratio 2.1, p=0.033) and combined margin status (odds ratio 10.8, p≤0.001) were independent risk factors for residual disease. In a subgroup analysis using depth of invasion ≤5mm and a negative combined margin, none (0%) of the 52 patients who met the criteria had residual disease. CONCLUSIONS: Conization (combined ectocervical and endocervical) margin and tumour depth of invasion are independent predictors of residual disease in hysterectomy specimens. A negative conization margin and depth of invasion ≤5mm are associated with low risk of residual disease in patients with early-stage cervical cancer.

A novel miR-193a-5p-YY1-APC regulatory axis in human endometrioid endometrial adenocarcinoma.

Aberrant expression and altered function of transcription factors (TFs) have vital roles in many aspects of tumor development and progression. In this study, we investigated the functional significance of a TF, Yin Yang1 (YY1) in tumorigenesis of endometrioid endometrial carcinoma (EEC). We demonstrated that YY1 is upregulated in EEC cell lines and primary tumors; and its expression is associated with tumor stages. Depletion of YY1 inhibits EEC cell proliferation and migration both in vitro and in vivo, whereas overexpression of YY1 promotes EEC cell growth. These results suggest that YY1 functions as an oncogenic factor in EEC. Transcriptome analysis revealed a significant effect of YY1 on critical aspects of EEC tumorigenesis through inhibition of APC expression. Further mechanistic investigation uncovered a new epigenetic silencing mode of APC by YY1 through recruitment of EZH2 and trimethylation of histone 3 lysine 27 on its promoter region. Moreover, YY1 overexpression was found to be a consequence of miR-193a-5p downregulation through direct miR-193a-5p-YY1 interplay. Our results therefore establish a novel miR-193a-5p-YY1-APC axis, which contributes to EEC development, and may serve as future intervention target.

Fos expression in the prefrontal cortex and ventral striatum after exposure to a free-operant timing schedule.

It has been proposed that cortico-striato-thalamo-cortical circuits that incorporate the prefrontal cortex and corpus striatum regulate interval timing behaviour. In the present experiment regional Fos expression was compared between rats trained under an immediate timing schedule, the free-operant psychophysical procedure (FOPP), which entails temporally regulated switching between two operanda, and a yoked variable-interval (VI) schedule matched to the timing task for food deprivation level, reinforcement rate and overall response rate. The density of Fos-positive neurones (counts mm(-2)) in the orbital prefrontal cortex (OPFC) and the shell of the nucleus accumbens (AcbS) was greater in rats exposed to the FOPP than in rats exposed to the VI schedule, suggesting a greater activation of these areas during the performance of the former task. The enhancement of Fos expression in the OPFC is consistent with previous findings with both immediate and retrospective timing schedules. Enhanced Fos expression in the AcbS was previously found in retrospective timing schedules based on conditional discrimination tasks, but not in a single-operandum immediate timing schedule, the fixed-interval peak procedure. It is suggested that the ventral striatum may be engaged during performance on timing schedules that entail operant choice, irrespective of whether they belong to the immediate or retrospective categories.

Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1.

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3'-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.

CHD5 Downregulation Associated with Poor Prognosis in Epithelial Ovarian Cancer.

BACKGROUND: The CHD5 gene located on 1p36 encodes a protein-chromodomain helicase DNA-binding protein 5. CHD5 has been shown to be a tumor suppressor gene candidate. This study investigated the involvement of CHD5 in ovarian cancer and its clinicopathological significance. METHODS: CHD5 expression in ovarian cancer and its counterpart were determined by quantitative RT-PCR. The correlation of CHD5 expression to clinicopathological features of the tumor was analyzed. RESULTS: CHD5 expression was downregulated by at least twofold in 32 of 72 (41%) invasive epithelial ovarian carcinomas when compared to 12 controls in Hong Kong Chinese women. CHD5 downregulation was correlated to clinical status (p < 0.05), but not to patient age, tumor type and grade, recurrence and clinical stage (p > 0.05). Survival analysis showed that patients with CHD5 downregulation in their tumors were associated with shorter disease-free and total survival times compared to those without CHD5 downregulation (p < 0.05). Cox proportional-hazards regression analysis indicated that downregulation of CHD5 is an independent adverse prognostic factor in ovarian cancer. CONCLUSION: This study shows that CHD5 is downregulated in a certain number of ovarian cancers and appears to be an adverse predictor candidate of ovarian cancer disease-free and total survival.

Nicotine-induced plasma corticosterone is attenuated by social interactions in male and female adolescent rats.

Most smokers begin smoking during adolescence, a period during which social reward is highly influential. Initial exposure to nicotine can produce anxiogenic effects that may be influenced by social context. This study examined play behavior and plasma corticosterone following nicotine administration (0.6 mg/kg, s.c.) in both male and female adolescent (PND39) Sprague-Dawley rats in either isolate or social contexts. In blood samples collected immediately following the 15-min test session, nicotine increased plasma corticosterone relative to saline in both male and female isolate rats, but failed to do so in both males and females placed together in same-sex pairs. Nicotine also attenuated several indices of play behavior including nape attacks, pins and social contact. In isolate rats, nicotine selectively increased locomotor activity in females; however, when administered to social pairs, nicotine decreased locomotion in both sexes. These findings suggest that the presence of a social partner may decrease the initial negative, stress-activating effects of nicotine, perhaps leading to increased nicotine reward.

T-cell response to human papillomavirus type 52 L1, E6, and E7 peptides in women with transient infection, cervical intraepithelial neoplasia, and invasive cancer.

The E6 and E7 proteins encoded by human papillomaviruses (HPV) are prime targets for therapeutic vaccine development. Ninety-five women with HPV 52 infection (33 transient infections, 17 cervical intraepithelial neoplasia grade II, 15 cervical intraepithelial neoplasia grade III, and 30 invasive cervical cancers) were examined for T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay. Of the 29 peptides (13 L1, 10 E6, and 6 E7) screened positive by an in vitro peptide-binding assay, 14 were positive by the IFN-γ ELISPOT assay. Positive epitopes for HLA A11 were located at amino acid positions 103-111, 332-340, 342-350, and 373-381 of the L1 protein; and at 27-35 and 86-94 of the E6 protein; and at 1-9 and 27-35 of the E7 protein. A24-specific epitopes included 60-68 and 98-106 of the L1 protein, 42-50 and 59-67 of the E6 protein, and 24-32 of the E7 protein. Only one epitope (99-107) of the E6 protein showed positive responses for HLA A2 subjects. Overall, T-cell responses against L1 were observed mainly in subjects who had cleared infection; whereas responses against E6 and E7 were confined mainly to subjects who had developed cervical neoplasia. The proportion of subjects showing detectable T-cell responses was low across all grades of cervical neoplasia suggesting that immune evasion mechanisms had set on early in the course of disease progression. This study provides the first set of T-cell epitopes mapped for HPV 52, which can be considered for further evaluation as targets for immunotherapy.

Laparoscopic sacrocolpopexy for the treatment of vaginal vault prolapse: with or without robotic assistance.

OBJECTIVE: To assess perioperative and medium-term outcome after laparoscopic sacrocolpopexy with or without robotic assistance for vaginal vault prolapse in a Hong Kong tertiary centre. DESIGN: Retrospective study. SETTING: An urogynaecology unit in Hong Kong. PATIENTS: All women who underwent laparoscopic sacrocolpopexy with or without robotic assistance for vaginal vault prolapse from March 2005 to May 2010. MAIN OUTCOME MEASURES: The perioperative and medium-term outcomes. RESULTS: A total of 36 women underwent the operation during the study period. The mean operating time was 205 minutes, mean blood loss was 144 mL. The median hospital stay was 4 days. Two women required early re-operation but recovered fully. In all, 35 women were followed up for 29 (standard deviation, 19) months. Three of them (9%) had a recurrence of stage II prolapse, but there was statistically significant improvement in the pelvic organ prolapse quantification assessment for all three compartments of the vagina, and the length of vagina was well preserved. There were no mesh exposure or erosions. The overall objective cure rate of 91% (32/35) was high, and 91% (32/35) were satisfied with the operative outcome. Stress incontinence and voiding difficulty were significantly reduced. CONCLUSION: Laparoscopic sacrocolpopexy for vaginal vault prolapse is safe, although complications arising from concomitant surgery should not be neglected. High rates of objective cures and patient satisfaction were achieved. There were no mesh exposure or erosions. Laparoscopic sacrocolpopexy should be considered an option for women with vaginal vault prolapse.

T-cell response to human papillomavirus type 58 L1, E6, And E7 peptides in women with cleared infection, cervical intraepithelial neoplasia, or invasive cancer.

Human papillomavirus type 58 (HPV-58) exists in a relatively high prevalence in certain parts of the world, including East Asia. This study examined the T-cell response to HPV-58 L1, E6, and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3, or invasive cervical cancer (ICC). Peptides found to be reactive in the in vitro peptide binding assay or mouse-stimulating study were tested with a gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay to detect peptide-specific responses from the peripheral blood mononuclear cells (PBMC) collected from 91 HPV-58-infected women (32 with cleared infection, 16 CIN2, 15 CIN3, and 28 ICC). Four HLA-A11-restricted HPV-58 L1 peptides, located at amino acid positions 296 to 304, 327 to 335, 101 to 109, and 469 to 477, showed positive IFN-gamma ELISPOT results and were mainly from women with cleared infection. Two HLA-A11-restricted E6 peptides (amino acid positions 64 to 72 and 94 to 102) and three HLA-A11-restricted E7 peptides (amino acid positions 78 to 86, 74 to 82, and 88 to 96) showed a positive response. A response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA-A2-restricted E6 peptide, located at amino acid position 99 to 107, elicited a positive response in two CIN2 subjects. One HLA-A24-restricted L1 peptide, located at amino acid position 468 to 476, also elicited a positive response in two CIN2 subjects. In summary, this study has identified a few immunogenic epitopes for HPV-58 E6 and E7 proteins. It is worthwhile to further investigate whether responses to these epitopes have a role in clearing an established cervical lesion.

Increase of integration events and infection loads of human papillomavirus type 52 with lesion severity from low-grade cervical lesion to invasive cancer.

Infection load and the integration of human papillomaviruses (HPV) have been implicated as determinants for oncogenesis, but whether variation among different HPV types exists remains unclear. We investigated 91 women infected with HPV type 52 (HPV-52), a type that is rare worldwide but common in East Asia. The median viral load increased with the severity of the lesion (248 copies/cell equivalent for normal/cervical intraepithelial neoplasia [CIN] grade 1, 402 copies/cell equivalent for CIN 2, 523 copies/cell equivalent for CIN 3, and 1,435 copies/cell equivalent for invasive cancer). The proportion of specimens with integration increased significantly with the severity of the lesion (P < 0.001). The viral load was associated with the physical status of the viral genome, with higher levels for the pure episomal form (P = 0.001). Infection status should be considered when interpreting viral load data for HPV-52, as single infections with this HPV type were found to have marginally higher viral loads than coinfections (P = 0.051). All except one sample had E2 disruption restricted to only a part of the gene. Integration is a critical step in HPV-52-induced carcinogenesis. The profile of E2 disruption was different from that described for HPV-16, with the amino-terminal region being most frequently involved. Selecting the appropriate E2 region for amplification is critical in studying the integration of HPV-52. In summary, the HPV-52 viral load and the integrated proportion increased with the severity of the cervical lesions but had a different pattern than that of HPV-16.

Patients with malignant or pre-malignant cervical lesion have increased risk of becoming hepatitis B carrier.

Human Papillomavirus (HPV) and Hepatitis B virus (HBV) are known aetiology of cervical and hepatocellular carcinoma, respectively. Both diseases share a similar clinical course, that is, the vast majority of those infected by these two viruses can eradicate the viruses spontaneously. A small sub-group who fails to clear the virus becomes chronic carrier and can progress to carcinoma many years later. We postulated that patients with pre-malignant or malignant cervical lesion are at increased risk of becoming chronic HBV carrier if infected, which may be attributed to inherent immunological deficiency against viral infection. We tested HBV carrier status from 288 patients with cervical carcinoma, 242 patients with high grade cervical intra-epithelial neoplasia (CIN) and 311 women with neither of the above conditions as control subjects. The HBV carrier rate in the Cancer Group, CIN Group and Control Group was 21.4%, 24.1% and 10.6%. The carrier rate was significantly higher in both the Cancer Group (p<0.01) and the CIN Group (p<0.01), compared to the Control Group. Our study suggests that a common immunological mechanism is involved in eradication of HBV and HPV infections and inherent immuno-deficiency might lead to an association of HBV carrier status with cervical carcinoma. Further studies are needed to confirm our findings and delineate the mechanism involved.

Is aortic lymphadenectomy necessary in the management of endometrial carcinoma?

OBJECTIVE: To evaluate the role of aortic lymphadenectomy in the management of endometrial carcinoma. METHODS: Clinical notes of 163 patients with endometrial carcinoma were reviewed. All patients had peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy with or without aortic lymphadenectomy. RESULTS: Seventy-five (46.0%) patients had pelvic lymphadenectomy alone whereas 88 (54.0%) had both pelvic and aortic lymphadenectomy. Thirty-five (21.5%) patients had nodal metastases with positive pelvic and aortic nodes in 26 (16.0%) and 24 (27.3%) patients, respectively. Isolated aortic metastases were found in 17 cases (19.3%). Among 35 patients with nodal metastases, recurrence developed in 15 (42.9%) patients and all except one died within five to 50 months. The remaining patients had a median disease-free period of 55 months (13-93 months). The recurrence rate was higher (63.6%) among patients with upper aortic lymph node metastases, and all those who recurred died of disease within seven to 28 months. CONCLUSIONS: Our data suggest that aortic lymphadenectomy provides both diagnostic and therapeutic value in the management of endometrial carcinoma with high metastatic risk. After surgical removal and adjuvant radiotherapy, patients with nodal metastases achieved a better survival chance.

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling.

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (>or=4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.

Gene expression pattern associated with radiotherapy sensitivity in cervical cancer.

UNLABELLED: The objective of the present preliminary study was to determine if a difference in the pattern of gene expression exists between tumors that were subsequently found to be sensitive to radiotherapy and tumors found to be resistant to radiotherapy. PATIENTS AND METHODS: A total of 16 patients with invasive squamous cell carcinoma of the uterine cervix were included in this study. All patients were treated with standardized radiotherapy alone. Ten of the tumors were clinically radiosensitive and six were radioresistant. Total RNA, extracted from tumor specimens obtained prior to treatment, was hybridized onto an oligonucleotide microarray with probe sets complementary to over 20,000 transcripts. The genes were first subjected to a statistical filter to identify genes with statistically significant differential expression levels between those that were radiosensitive and those that were radioresistant. A back-propagation neural network was then constructed to model the differences so that patterns could be easily identified. RESULTS: Although a number of genes were found to express differentially between radiosensitive and radioresistant tumors; the 10 most discriminating genes were used to construct the model. Using the expressions from these 10 genes, we found that neural networks constructed from random subsets of the whole data were capable of predicting radiotherapy responses in the remaining subset, which appears stable within the dataset. DISCUSSION: This study shows that such an approach has the potential to differentiate tumor radiosensitivity, although confirmation of such a pattern using other larger independent datasets is necessary before firm conclusions can be drawn.

Prospective self-controlled study on prevention of hysteroscopic dissemination in endometrial carcinoma.

Patients diagnosed to have endometrial carcinoma without prior hysteroscopic examination were recruited from March 2000 to August 2003. Normal saline was used to distend the uterine cavity during the hysteroscopic examination to look for endocervical spread before the definitive surgical treatment. We performed laparotomy, clamped both fallopian tubes, and collected peritoneal washing before the hysteroscopic examination was performed. Peritoneal washing was collected once more after the hysteroscopic examination. Hysteroscopic assessment was performed in 103 patients. Of them, 10 patients were excluded from the study due to previous history of tubal sterilization or blockage. The final analysis was confined to 93 patients. Positive peritoneal cytology was found in 10 (10.8%) patients and this finding was significantly related to the tumor grading (P = 0.023), adnexal involvement (P = 0.003), cervical invasion (P = 0.01), and the presence of peritoneal seedlings (P = 0.001). In five of the 10 patients with positive peritoneal cytology before the hysteroscopic examination, malignant cells could also be recovered in the peritoneal washing collected after the hysteroscopic examination. For patients with negative peritoneal cytology before hysteroscopy, none exhibited positive peritoneal cytology after the procedure. Our data suggested that complete occlusion of both fallopian tubes can effectively prevent the dissemination of endometrial malignant cells into the peritoneal cavity during hysteroscopy.

Protein profiling of cervical cancer by protein-biochips: proteomic scoring to discriminate cervical cancer from normal cervix.

Analysis of multiple proteins is thought to be essential for establishment of signature proteomic patterns that may distinguish cancer from non-cancer. Surface-enhanced laser desorption/ionization (SELDI) is an affinity-based mass spectrometric method in which proteins of interest are selectively absorbed to a chemically modified surface on a biochip. This technology may provide protein profiling of a variety of biological specimens. In this study, we explored whether the protein biochip SELDI approach could differentiate cervical cancer from non-cancer cohorts. We screened protein profiles generated by SELDI in 62 cervical epithelial cell samples microdissected from 35 invasive cervical cancer and 27 age-matched normal cervix tissue specimens, respectively. The cell lysates of pure populations of cervical cells were applied onto Ciphergen ProteinChip WCX2 Arrays. Proteins bound to the chips were analyzed on a ProteinChip Reader Model PBS II. Derived proteomic patterns were converted to a simple proteomic scoring for distinguishing cancer from non-cancer cohorts. SELDI protein profiles of cell lysates from 20 cervical cancer and 15 normal cervix tissue specimens were used to train and develop a classification scoring system that used a seven-protein mass pattern. The training samples could be correctly discriminated. When a test set of 27 samples was used for evaluation of this scoring system to distinguish cervical cancer from non-cancer, a sensitivity of 87%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 86% for the test population were obtained. All seven proteins appeared to be down regulated in cervical cancer. The results from this study indicate that the proteomics approach of SELDI mass spectrometry, in combination with a simple scoring system, may distinguish cervical cancer from its normal counterpart. If this approach is also workable in the analysis of cervical exfoliated cell lysate, it might potentially be used in the early diagnosis of invasive cervical cancer. In addition, the identification of these specific proteins in cervical cancer may also facilitate the discovery of new cervical tumor marker(s).

Patient-controlled analgesia versus conventional intramuscular injection: a cost effectiveness analysis.

BACKGROUND: In previous studies comparing patient-controlled-analgesia and intramuscular pain management have been unable to provide conclusive evidence of the benefits of either method of postoperative pain control. AIM: The purpose of the study was to compare the efficacy and cost-effectiveness of intravenous patient-controlled-analgesia with intermittent intramuscular morphine for Chinese women in the first 24 hours following elective gynaecological surgery. METHODS: A randomized control design was used. The main outcomes were level of pain and cost for the two types of pain management. Participants indicated their level of pain at rest and when deep breathing or coughing on a 100 mm Visual Analogue Scale, on seven occasions within 24 postoperative hours. Costs for the two types of pain management were based on the costs of equipment, drugs and nursing time. RESULTS: A total of 125 women participated in the study. Mean pain level over the 24 hours in the patient-controlled-analgesia group was significantly lower than in the intramuscular group (P < 0.001). Mean pain level over the seven occasions for the patient-controlled-analgesia group was 11.83 points (95% CI 7.14-16.52) lower when at rest and 11.73 points (95% CI 5.96-17.50) lower during motion than the intramuscular group. Cost per patient was $81.10 (Hong Kong) higher for patient-controlled-analgesia than for intramuscular pain management. Women in the patient-controlled-analgesia group had significantly greater satisfaction with pain management than those in the intramuscular group (P < 0.001), but reported significantly more episodes of nausea (P < 0.05). CONCLUSIONS: While patient-controlled-analgesia was more costly, it was also more effective than conventional on-demand intramuscular opioid injections after laparotomy for gynaecological surgery.