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1.
Cancers (Basel) ; 13(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203201

RESUMO

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient's circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women's cancer.

2.
J Clin Virol ; 114: 32-36, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30913520

RESUMO

BACKGROUND: A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. OBJECTIVES: To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. STUDY DESIGN: Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. RESULTS: The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 µL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. CONCLUSIONS: HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , DNA Viral/análise , Biópsia Líquida/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Proteínas do Capsídeo/genética , Carcinoma de Células Escamosas/virologia , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/complicações , Recidiva , Estudos Retrospectivos , Neoplasias do Colo do Útero/virologia , Carga Viral
3.
Gynecol Oncol ; 146(2): 334-339, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28587748

RESUMO

INTRODUCTION: Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. METHODS: One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. RESULTS: PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size (p<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05). CONCLUSIONS: As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , DNA de Neoplasias/sangue , Fosfatidilinositol 3-Quinases/genética , Neoplasias do Colo do Útero/sangue , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Povo Asiático , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Carga Tumoral , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
4.
PLoS One ; 11(8): e0160412, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27494141

RESUMO

We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients' plasma: 60-64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Osteopontina/metabolismo , Neoplasias do Colo do Útero/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/metabolismo , Biomarcadores Tumorais/sangue , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Osteopontina/genética , Osteopontina/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Trombina/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
5.
Hong Kong Med J ; 21(4): 333-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26183453

RESUMO

OBJECTIVES: To compare the 5-year subjective and objective outcomes of transobturator tension-free vaginal tape alone versus the same procedure with concomitant pelvic floor repair surgery for pelvic organ prolapse in women with urinary stress incontinence. DESIGN: Prospective cohort study. SETTING: Urogynaecology unit at a university hospital in Hong Kong. PATIENTS: Of 218 women, 96 (44%) received transobturator tension-free vaginal tape alone and 122 (56%) received transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery from September 2004 to December 2009. The women were followed up annually for up to 5 years after the operation. MAIN OUTCOME MEASURES: The 5-year subjective and objective cure rates were assessed. Subjective cure was defined as no urine loss during physical activity and objective cure was defined as no urine leakage on coughing during urodynamic study. RESULTS: Overall, 88 women receiving transobturator tension-free vaginal tape alone and 101 women receiving transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery were followed up for 5 years after operation. The subjective and objective cure rates of the two groups were 70.5% versus 94.1% (P<0.01) and 80.3% versus 85.7% (P=0.58), respectively. CONCLUSIONS: Transobturator tension-free vaginal tape is an effective treatment for urinary stress incontinence in women who received it alone or with concomitant pelvic floor repair surgery for pelvic organ prolapse, providing high subjective and objective efficacy for up to 5 years after operation. Transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery achieved similar, if not better, long-term outcome compared with transobturator tension-free vaginal tape alone.


Assuntos
Diafragma da Pelve/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Slings Suburetrais/estatística & dados numéricos , Incontinência Urinária por Estresse/cirurgia , Vagina/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
6.
Int J Cancer ; 137(4): 776-83, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25626421

RESUMO

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.


Assuntos
Adenocarcinoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias do Colo do Útero/genética , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adulto , Idoso , Exoma , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
7.
Endocr Relat Cancer ; 21(3): R227-33, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24623744

RESUMO

Each year, ∼25 000 women are newly diagnosed with ovarian cancer in the USA. The vast majority (>90%) of cases are of epithelial origin. This highly lethal cancer carries a mortality rate of >50% and a high risk of recurrence after conventional, first-line chemotherapy. Müllerian-inhibiting substance (MIS) is a gonadal hormone that causes regression of the Müllerian ducts. A series of studies have demonstrated that MIS also has multiple extra-Müllerian functions including inhibition of epithelial ovarian cancer cells in vitro and in vivo. Accumulating evidence has shown that many human cancers are organized hierarchically and contain a small population of cancer stem cells (CSCs) that are inherently resistant to common chemotherapy and radiation therapy. The effect of MIS on ovarian CSC seems to be particularly useful in rescuing ovarian cancer patients with resistance to conventional treatment. Based on recent studies evaluating MIS, this review updates our current understanding of the molecular genetic aspects of MIS, its pathophysiology, as well as its potential to treat chemoresistant epithelial ovarian cancer.


Assuntos
Hormônio Antimülleriano/uso terapêutico , Ductos Paramesonéfricos/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Animais , Feminino , Humanos
8.
J Pediatr Adolesc Gynecol ; 27(3): 166-71, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24656700

RESUMO

OBJECTIVE: To investigate the effects of 4-month treatment of medroxyprogesterone acetate (MPA) and Diane-35 on the clinical and biochemical features of hyperandrogenism and quality of life of adolescent girls with polycystic ovarian syndrome (PCOS). DESIGN: A prospective, randomized, cross-over study. SETTING: An accredited pediatric and adolescent gynecology clinic of a university-affiliated tertiary hospital. PARTICIPANTS: 76 adolescents girls aged 14 to 19 years old with PCOS were recruited from July 2007 to July 2010. INTERVENTIONS: Girls were randomized into 2 groups. Group 1 received oral MPA for 4 months, followed by a washout period of 4 months, and then Diane-35 for another 4 months. Group 2 received the same combination but in the reverse order. MAIN OUTCOME MEASURES: Clinical and biochemical features of hyperandrogenism and quality of life were assessed. RESULTS: There was no significant difference between the 2 groups at baseline. No significant difference was found in the clinical and biochemical parameters of hyperandrogenism before and after treatment with MPA. Significant reduction of the acne score, LH/FSH ratio, and testosterone level was seen after taking Diane-35. Hirsutism was also improved but it did not reach statistical significant. When comparing post-MPA and post-Diane-35, the post-Diane-35 group had significantly improved acne score and LH/FSH ratio. No significant difference was found on quality of life between both groups after treatment. CONCLUSION: Diane-35 may be a more suitable treatment option in adolescent girls diagnosed with PCOS when compared to MPA.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Acetato de Ciproterona/uso terapêutico , Etinilestradiol/uso terapêutico , Hiperandrogenismo/tratamento farmacológico , Acetato de Medroxiprogesterona/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Qualidade de Vida , Acne Vulgar/tratamento farmacológico , Adolescente , Estudos Cross-Over , Combinação de Medicamentos , Feminino , Hormônio Foliculoestimulante/sangue , Hirsutismo/tratamento farmacológico , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/etiologia , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Estudos Prospectivos , Índice de Gravidade de Doença , Testosterona/sangue , Adulto Jovem
9.
Hong Kong Med J ; 19(6): 511-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23784533

RESUMO

OBJECTIVE: To assess perioperative and short-term outcomes after tension-free vaginal mesh repair of pelvic organ prolapse in local Chinese women. DESIGN: Case series. SETTING: The urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS: All women with stage III or more pelvic organ prolapse who underwent tension-free vaginal mesh repair with or without vaginal hysterectomy from May 2007 to June 2011. MAIN OUTCOME MEASURES: Perioperative and short-term outcomes. RESULTS: In all, 47 women underwent the procedure during the study period. The mean operating time was 94 minutes, the mean estimated blood loss was 163 mL, and the mean hospital stay was 4 days. Four patients had visceral injuries, all of which were identified and repaired during the operation; all four patients recovered uneventfully. The mean duration of follow-up was 25 (standard deviation, 13) months. Pelvic organ prolapse quantification improved significantly; nine (19%) of the patients had recurrent stage II prolapse but only one was symptomatic, six (13%) had postoperative mesh exposure, three of whom underwent mesh excision. There were five (11%) who had de-novo urodynamic stress incontinence, which was mostly mild and managed conservatively. Overall 91% (43/47) were satisfied with their operative outcome. CONCLUSIONS: The success rate of tension-free vaginal mesh repair for the treatment of pelvic organ prolapse in local Chinese women was comparable to rates reported internationally. There was a high degree of subjective satisfaction with the procedure. There were low rates of mesh exposure and de-novo stress incontinence that was mostly asymptomatic or mild.


Assuntos
Histerectomia Vaginal , Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas , Incontinência Urinária por Estresse/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Hong Kong , Humanos , Pessoa de Meia-Idade , Duração da Cirurgia , Satisfação do Paciente , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Urodinâmica
10.
Aust N Z J Obstet Gynaecol ; 53(2): 190-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23316927

RESUMO

AIMS: To evaluate the risk of missing a malignancy in surgical specimens following hysterectomy for uterine prolapse if routine pathological examination is not performed. Additionally, information on the risk of missing an hitherto unsuspected malignancy if uterine preservation is the preferred management option will be provided. MATERIALS AND METHODS: A retrospective study was performed on all cases of surgery performed for uterine prolapse in a tertiary referral institution from 2003 to 2011. Those with confirmed malignancy before operation were excluded. The study subjects had their clinical history, investigations, the type of operations and histopathology report analysed. They were classified into symptomatic or asymptomatic, depending on whether they reported symptoms that were suggestive of uterine malignancy. RESULTS: A total of 640 women were studied. Three cases of hitherto unsuspected uterine malignancy were found, giving an incidence of 0.47%. Among the 456 asymptomatic women, both pre- and postmenopausal, the risk of incidental malignancy was 0.22%. Within the postmenopausal group, risk of incidental malignancy was 0.26%. Another 3 cases of uterine premalignant conditions were identified, giving an overall risk of premalignant and malignant uterine condition of 0.94%. Five cases of cervical intra-epithelial neoplasia were found, contributing to a risk of 0.78%. CONCLUSIONS: The risk of missing an uterine malignancy in patients with uterine prolapse is low if appropriate investigations are carried out prior to surgery. If hysterectomy is to be performed, we recommend that all surgical specimens be subjected to histopathological examination.


Assuntos
Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Leiomiossarcoma/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Prolapso Uterino/cirurgia , Útero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Feminino , Humanos , Histerectomia , Achados Incidentais , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Cell Cycle ; 11(15): 2876-84, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22801550

RESUMO

MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.


Assuntos
MicroRNAs/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Transformação Celular Neoplásica/genética , Colo do Útero/metabolismo , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia
12.
Hong Kong Med J ; 18(3): 214-20, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22665685

RESUMO

OBJECTIVES: To evaluate the quality of life in women with urinary incontinence (categorised by urodynamic findings). DESIGN: Prospective cohort study on patients. SETTING: Urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS. Female patients presenting to our clinic from July 2008 to December 2009 and having their urinary incontinence categorised by urodynamic study. MAIN OUTCOME MEASURES: Patient's quality of life was assessed using the Medical Outcomes Study Short Form, Urogenital Distress Inventory Short Form, and Incontinence Impact Questionnaire Short Form. Their quality of life was compared according to their urodynamic category and a subgroup analysis was performed on patients having continence surgery for urodynamic stress incontinence. RESULTS: Among the 223 women studied, 46% had urodynamic stress incontinence, 18% had detrusor overactivity, 2% had both urodynamic stress incontinence and detrusor overactivity, and 34% had no urodynamic abnormality. In all, the Medical Outcomes Study Short Form scoring was lower than normal local population. The Medical Outcomes Study Short Form score in detrusor overactivity group was significantly lower than urodynamic stress incontinence group in vitality and mental health domains. Detrusor overactivity group also had higher scores in Incontinence Impact Questionnaire Short Form in travel, social and emotional health subscales and total score (46.3 vs 29.1; P<0.01). Women with urodynamic stress incontinence and required continence surgery had higher scores in Incontinence Impact Questionnaire Short Form. CONCLUSION: Women with urinary incontinence had impaired quality of life and it was comparable to other chronic medical diseases. Women with detrusor overactivity have more impaired quality of life than women with urodynamic stress incontinence. Severity of urodynamic stress incontinence did not correlate with quality of life. Women who opted for continence surgery had poorer quality of life.


Assuntos
Doença Crônica/psicologia , Qualidade de Vida , Incontinência Urinária/psicologia , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Urodinâmica
13.
Hong Kong Med J ; 17(5): 391-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21979477

RESUMO

OBJECTIVE. To study the presentations, diagnoses, and outcomes in adolescents with menstrual disorders. DESIGN. Prospective cohort study. SETTING. Paediatric and Adolescent Gynaecology Clinic, Hong Kong. PARTICIPANTS. A total of 577 adolescents aged 14 to 19 years. MAIN OUTCOME MEASURES. The presentations and diagnoses of adolescents with menstrual disorders were reviewed and their menstrual outcomes determined by a telephone survey. RESULTS. In all, 47% presented with menorrhagia, prolonged menstruation, and short menstrual cycles; 27% had secondary amenorrhoea, 12% had dysmenorrhoea, 11% had oligomenorrhoea, and 3% had primary amenorrhoea. Significant diagnoses included congenital genital tract anomalies, premature ovarian failure, anorexia nervosa, and polycystic ovarian syndrome. Polycystic ovarian syndrome was diagnosed in 16% of the cohort. In all, 24% of these 577 patients had abnormal menstrual cycles 4 years later. Direct logistic regression analysis indicated a cycle length of more than 35 days at presentation (adjusted odds ratio=2.8; 95% confidence interval, 1.8-4.5), previous diagnosis of polycystic ovarian syndrome (adjusted odds ratio=2.0; 95% confidence interval, 1.1-3.4), and current body mass index of 23 kg/m(2) or higher (adjusted odds ratio=1.8; 95% confidence interval, 1.0-3.0) were risk factors for persistently long menstrual cycle exceeding 35 days. Adolescents who were screened out with a definitive diagnosis after initial assessment were at low risk of persistently long menstrual cycles at follow-up (adjusted odds ratio=0.3; 95% confidence interval, 0.1-0.8). CONCLUSIONS. Adolescent menstrual disorders should not be ignored. Long cycle, diagnosis of polycystic ovarian syndrome at first consultation, and a current body mass index of 23 kg/m(2) or higher were statistically associated with persistent problems.


Assuntos
Ciclo Menstrual , Distúrbios Menstruais/diagnóstico , Distúrbios Menstruais/etiologia , Transtornos 46, XX do Desenvolvimento Sexual/complicações , Anormalidades Múltiplas , Adolescente , Adulto , Anorexia Nervosa/complicações , Índice de Massa Corporal , Anormalidades Congênitas , Exercício Físico , Feminino , Humanos , Rim/anormalidades , Modelos Logísticos , Estudos Longitudinais , Ductos Paramesonéfricos/anormalidades , Síndrome do Ovário Policístico/complicações , Insuficiência Ovariana Primária/complicações , Estudos Prospectivos , Fatores de Risco , Somitos/anormalidades , Coluna Vertebral/anormalidades , Estresse Psicológico/complicações , Inquéritos e Questionários , Fatores de Tempo , Útero/anormalidades , Vagina/anormalidades , Redução de Peso , Adulto Jovem
14.
Gynecol Obstet Invest ; 72(3): 203-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21860208

RESUMO

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.


Assuntos
DNA Helicases/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Epiteliais e Glandulares/genética , Proteínas do Tecido Nervoso/genética , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida
15.
Qual Life Res ; 19(7): 931-41, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20449666

RESUMO

PURPOSE: The aim of the study was to examine the role of neuroticism and mastery in predicting the quality of life (QOL) among Chinese gynecologic cancer survivors. METHODS: A total of 184 women participated in this prospective longitudinal study. Participants were to rate their quality of life at baseline (T1) and one year later (T2). Neuroticism as a predictor of QOL was examined by controlling for baseline QOL, sociodemographic, and disease variables using hierarchical linear regression modeling. Mastery as a mediator between the relationship of neuroticism and QOL was also examined. RESULTS: Bivariate correlations showed that the cancer site, time since diagnosis, neuroticism, and mastery at T1 were related to various aspects of QOL at T1 and T2. After controlling for cancer site, time since diagnosis, QOL at T1, high levels of neuroticism at T1 predicted poor physical and emotional QOL at T2, but mastery at T1 did not mediate the relationship between neuroticism at T1 and QOL at T2. CONCLUSIONS: Neuroticism is a salient personality variable that predicts poor emotional and physical well-being over time. Gynecologic cancer survivors high on neuroticism should be the target for intervention to reduce negative effects during the course of recovery.


Assuntos
Adaptação Psicológica , Neoplasias dos Genitais Femininos/psicologia , Transtornos Neuróticos , Qualidade de Vida , Adulto , Feminino , Hong Kong , Humanos , Entrevistas como Assunto , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Estresse Psicológico , Sobreviventes/psicologia
16.
Arch Sex Behav ; 39(5): 1191-200, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19757013

RESUMO

This study investigated sexual drive and satisfaction of Chinese gynecologic cancer survivors. It also examined the extent to which personal mastery, adaptive coping, and perceived spousal support would exert direct and/or indirect influences on sexual outcomes. The cancer survivor group included 134 Chinese women who had received treatment for gynecologic cancer, while the healthy control group included 105 Chinese women who did not have a known history or current diagnosis of cancer. Compared to healthy women, cancer survivors reported lower levels of sexual drive and sexual satisfaction. Among sexually active participants, cancer survivors relative to healthy women engaged in less masturbation, less kissing and caressing, and less sexual fantasy in the past month. Hierarchical multiple regression analyses showed that mastery and spousal support, but not adaptive coping, had a direct influence on sexual outcomes in cancer survivors. Contrary to moderation hypotheses, the three psychological factors did not interact with each other to influence sexual drive and satisfaction. Mediation analyses showed that spousal support fully mediated the influence of mastery on sexual satisfaction. Routine assessment of sexual functioning prior to and following treatment of gynecologic cancer is suggested. Sexual rehabilitation should also aim to enhance personal mastery and spousal support.


Assuntos
Adaptação Psicológica , Neoplasias dos Genitais Femininos/psicologia , Libido , Satisfação Pessoal , Cônjuges/psicologia , Adulto , Idoso , Povo Asiático , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Análise de Regressão , Autoimagem , Comportamento Sexual/psicologia , Saúde da Mulher
17.
Support Care Cancer ; 17(3): 271-8, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18581149

RESUMO

GOALS OF WORK: The objective of the study was to examine quality of life (QOL) and its age-specific factors in cervical cancer patients at different stages of life. MATERIALS AND METHODS: One hundred and seventy-three Chinese patients with cervical cancer were surveyed by telephone. QOL was assessed with the WHO Quality of Life Scale-Chinese/Hong Kong (HK) version (WHOQOL-BREF-HK) and compared across age groups. Using multiple regression analyses, demographic and medical factors that were independently associated with QOL outcomes in each age group were identified. MAIN RESULTS: The age groups did not differ in the level of QOL, except for the social relationship domain. Older patients reported poorer social functioning than younger patients. Different factors were associated with QOL outcomes in different age groups. For patients in young adulthood, employment and education level were positively associated with QOL. For patients in midlife adulthood, time since diagnosis and stage of cancer were positively associated with QOL. For patients in aging adulthood, QOL was negatively associated with age, physical morbidity, and a history of termination of pregnancy. However, having a partner and possessing religious belief were positively associated with QOL. CONCLUSIONS: Patient's age had a significant impact on the experience of QOL. Older patients had poorer social relationships than younger patients. Religion seemed to have a protective effect against poor social functioning in aging patients.


Assuntos
Qualidade de Vida , Neoplasias do Colo do Útero/psicologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , China , Demografia , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Regressão , Inquéritos e Questionários
18.
Int J Cancer ; 124(6): 1358-65, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19065659

RESUMO

The objective of this study, a parallel study to global gene expression profiling, was to identify dysregulated microRNAs (miRNAs) associated with endometrioid endometrial adenocarcinoma (EEC), examine their correlation with clinico-pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome-wide gene expression had been previously profiled and reported. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub-group of miRNAs was significantly correlated with clinico-pathological characteristics including stage, myometrial invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets that were linked to the dysregulated genes previously identified, 68 genes were predicted as candidate targets of these 30 dysregulated miRNAs. miR-205 was significantly overexpressed in EECs compared with normal controls. After transfection of a miR-205 inhibitor, the expression of miR-205 in endometrial cancer cell line RL95-2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression. JPH4 seems to be a real miR-205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based on this study in EEC, miRNAs predicted to be involved in tumorigenesis and tumor progression have been identified and placed in the context of the transcriptome of EEC. This work provides a framework on which further research into novel diagnosis and treatment of EEC can be focused.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Carcinoma Endometrioide/patologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/patologia , Endométrio/citologia , Endométrio/patologia , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Valores de Referência
19.
Gynecol Oncol ; 105(3): 736-41, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17379283

RESUMO

OBJECTIVES AND METHODS: HLA II DQB1 polymorphisms have been shown to associate with cervical cancer risk, but results varied among different populations. In this study, the HLA DQB1 alleles among 221 southern Chinese women with cervical intraepithelial neoplasia grade III (CIN III)/invasive cervical carcinoma (ICC) were compared to 191 controls. RESULTS: The frequency of DQB1*03 was significantly lower among ICC overall as compared to controls (65.4% vs. 79.1%, odds ratio [95% confidence interval]: 0.50 [0.28-0.88], corrected p-value: 0.04). The protective association of DQB1*03 remained significant for human papillomavirus (HPV) 16-positive ICC, but not for HPV16-negative cases. This is in contrast to studies on European populations where DQB1*03 was associated with an increased risk for ICC. In the current study, 70.1% of the HPV16 isolates were Asian variants, and 28.0% were European variants. However, no significant association between HPV16 variant and DQB1*03 distribution was observed. HPV52 and HPV58 were found respectively in 16.3% and 10.0% of CIN III/ICC, which were higher compared to that of Europe and North America. Further analyses revealed a positive risk association between DQB1*06 and HPV58-positive CIN III/ICC (3.68 [1.37-9.92], corrected p-value: 0.012). CONCLUSION: The host genetics and the distribution of HPV types/variants may account for the observed differences among southern Chinese and other populations.


Assuntos
Antígenos HLA-DQ/genética , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/imunologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Adulto , Idoso , Alelos , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Cadeias beta de HLA-DQ , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Polimorfismo Genético , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/virologia
20.
Methods Mol Biol ; 385: 87-101, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18365706

RESUMO

Cervical cancer is still the leading cause of gynecological cancer deaths worldwide in spite of the advent of early diagnosis with the Pap smear. Ninety-five percent of cervical cancers are of squamous cell origin. Cervical carcinoma is almost always associated with infection from oncogenic subtypes of human papillomavirus (HPV). However, HPV infection alone is insufficient for malignant transformation; other genetic events independent or in conjunction with HPV infection are required. The early studies of genetics in cervical cancer were often hampered because only a few genes or genetic events could be evaluated at a time. Therefore, the interactions of multiple genes throughout the genome could not be evaluated. Gene-expression profiling utilizing microarrays allows quantitative measurement of the expression of thousands to all human expressed genes simultaneously. Here we describe how to obtain information on global genetic events in cervical cancer using oligonucleotide microarrays in combination with real-time reverse transcriptase polymerase chain reaction (RT-PCR). This facilitates understanding of the gene expression differences that underlie cervical neoplastic development and progression and can identify molecular signatures that can potentially be used in cervical cancer diagnosis and prognosis. This technology also represents a leap forward in the goal to eventually provide tailored therapy to individual patients and offers a genetic blueprint for gauging the potential effectiveness of all common cervical cancer treatments.


Assuntos
Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Feminino , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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