BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma.

Patients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapies. We report here the identification and characterisation of BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealed BCL11A to be upregulated in LUSC but not in lung adenocarcinoma (LUAD). Experimentally we demonstrate that non-physiological levels of BCL11A in vitro and in vivo promote squamous-like phenotypes, while its knockdown abolishes xenograft tumour formation. At the molecular level we found that BCL11A is transcriptionally regulated by SOX2 and is required for its oncogenic functions. Furthermore, we show that BCL11A and SOX2 regulate the expression of several transcription factors, including SETD8. We demonstrate that shRNA-mediated or pharmacological inhibition of SETD8 selectively inhibits LUSC growth. Collectively, our study indicates that BCL11A is integral to LUSC pathology and highlights the disruption of the BCL11A-SOX2 transcriptional programme as a novel candidate for drug development.

Lipschütz Genital Ulceration as Initial Manifestation of Primary Sjögren's Syndrome.

Genital ulcers are challenging to any clinician and causes transcend many specialties. Skin ulceration in patients with primary Sjögren's syndrome is infrequent but an established feature of cutaneous involvement. Although gynecological symptoms, such as vulvovaginal dryness, dyspareunia, and pruritus, are common in women with primary Sjögren's syndrome, patients affected by vulvar ulcers are unknown. We describe an exceptional case of necrotic aphthous-type vulvar ulceration as initial presentation of primary Sjögren's syndrome that was possibly triggered by an infectious agent. Successful healing was achieved with oral corticosteroids, despite some loss of labia minora and labia majora as sequelae of the necrotizing process. Reactive acute genital ulcers (Lipschütz ulcers) should be considered as a possible manifestation of many autoimmune/inflammatory disorders, beyond the classic associations such as Behçet's syndrome or Crohn's disease.

SOX2 Drives Bronchial Dysplasia in a Novel Organotypic Model of Early Human Squamous Lung Cancer.

RATIONALE: Improving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown that amplification of sex-determining region Y-box 2 (SOX2) is an early and consistent event in the pathogenesis of this disease, but its functional oncogenic potential remains uncertain. We tested the impact of deregulated SOX2 expression in a novel organotypic system that recreates the molecular and microenvironmental context in which squamous carcinogenesis occurs. OBJECTIVES: (1) To develop an in vitro model of bronchial dysplasia that recapitulates key molecular and phenotypic characteristics of the human disease; (2) to test the hypothesis that SOX2 deregulation is a key early event in the pathogenesis of bronchial dysplasia; and (3) to use the model for studies on pathogenesis and chemoprevention. METHODS: We engineered the inducible activation of oncogenes in immortalized bronchial epithelial cells. We used three-dimensional tissue culture to build an organotypic model of bronchial dysplasia. MEASUREMENTS AND MAIN RESULTS: We recapitulated human bronchial dysplasia in vitro. SOX2 deregulation drives dysplasia, and loss of tumor promoter 53 is a cooperating genetic event that potentiates the dysplastic phenotype. Deregulated SOX2 alters critical genes implicated in hallmarks of cancer progression. Targeted inhibition of AKT prevents the initiation of the dysplastic phenotype. CONCLUSIONS: In the appropriate genetic and microenvironmental context, acute deregulation of SOX2 drives bronchial dysplasia. This confirms its oncogenic potential in human cells and affords novel insights into the impact of SOX2 deregulation. This model can be used to test therapeutic agents aimed at chemoprevention.

ASC-H cytological result: clinical relevance and accuracy of colposcopy in predicting high-grade histological lesions-a 7-year experience of a single institution in Portugal.

INTRODUCTION: Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) represents an interpretative challenge in clinical practice. We aimed to evaluate the histological outcome of ASC-H cytology and to evaluate the accuracy of colposcopy in predicting high-grade histological lesions. MATERIALS AND METHODS: Retrospective study of ASC-H cervical cytology results, from January 2010 to December 2016, at a tertiary hospital. Demographic characteristics, colposcopic findings, diagnostic procedures, and histological outcomes were analyzed using SPSS, version 22.0. RESULTS: ASC-H prevalence was 0.25%. Patient mean age was 42.02 ± 12.8 years. The overall incidence of cervical dysplasia of any grade was 83.6% (n = 56) and the incidence of high-grade lesions was 50.8% (n = 34) (including 1 case of in situ adenocarcinoma and 2 cases of squamous cell carcinoma). Among patients with type 1 or 2 transformation zone (TZ), 84.9% (n = 45) had abnormal colposcopic findings, with 62.2% (n = 28) corresponding to grade 2 and 37.8% (n = 17) to grade 1. Colpo-histologic concordance was 85.4% (82.1% for grade 2 lesions and 100% for grade 1 lesions). The sensitivity, specificity, positive predicted value (PPV) and negative predictive value (NPV) was 100%, 75%, 82.1%, and 100%, respectively. The histological study of patients with type 3 TZ revealed 45.8% (n = 11) of high-grade lesions. CONCLUSIONS: ASC-H is strongly associated with high-grade histological lesions. Immediate evaluation of patients with this cytology abnormality is therefore mandatory. Colposcopy, when performed by expert clinicians, has great accuracy in detecting high-grade lesions. Histological evaluation of patients with type 3 TZ is extremely important because almost 50% of patients have this type of lesion.

Glassy cell carcinoma of the cervix and metastasis in episiotomy scar: a case report.

OBJECTIVE: The authors describe the 20th known case of cervical cancer with metastasis in an episiotomy scar, being the first case describing an implant of malignant cells in the episiotomy scar associated with glassy cell carcinoma. MATERIALS AND METHODS: One case report. RESULTS: We describe the case of a 34-year-old woman, with cervical cancer diagnosed 1 month after delivery. Four months later, a radical hysterectomy was performed. During surgery, a nodule at the site of the episiotomy scar was identified and removed. The histologic diagnosis revealed a glassy cell carcinoma of the cervix, with metastasis in the episiotomy scar. After surgery, chemotherapy and radiotherapy were performed. The disease progressed rapidly, and the patient died 9 months after surgery. CONCLUSIONS: The implantation of neoplastic cells in the perineum is a potential risk of vaginal delivery, with a 40% mortality rate. It thus seems advisable to avoid vaginal delivery as much as possible when cervical cancer is diagnosed during pregnancy. Given the rarity, there are no studies on the most effective treatment in such situations.

Cervical cancer in pregnancy: 3 cases, 3 different approaches.

OBJECTIVE: Cervical cancer is one of the most common malignancies in pregnancy and one percent of women diagnosed with cervical cancer are pregnant or postpartum at the time of the diagnosis. We discuss how pregnancy will affect the management of cancer, and cancer will affect the management of the pregnancy. MATERIAL AND METHODS: Three case reports. RESULTS: We report three cases, with three different approaches of pregnant patient with cervical carcinoma stage IB1, diagnosed below-20 weeks gestation. In two cases, the patients decided to continue the pregnancy. CONCLUSIONS: Cervical cancer in pregnancy is a clinical challenge. Once the diagnosis, the stage and the extent of invasive cervical cancer have been established, a multidisciplinary approach is required. Decisions regarding timing of treatment and delivery require careful considerations, as well as the trimester in which the diagnosis is made. Delaying definitive treatment to improve fetal outcome, may carry an additional risk of tumor progression, although a delay in definitive treatment is regarded as feasible. Delayed treatment is safe in patients with small sized, early stage disease, if there is no evidence of disease progression. Neoadjuvant chemotherapy during pregnancy is still controversial. Cesarean delivery followed by radical hysterectomy is recommended. The effect of cervical cancer on pregnancy outcome is still not clear.

Magnetic resonance imaging and gynecological devices.

BACKGROUND: Performing magnetic resonance imaging (MRI) on women with gynecological devices is a completely accepted practice. The goal of our review is to assess how safe it is to perform MRI on women using contraceptive implants or devices. STUDY DESIGN: Literature review, searching in PubMed-Medline/Ovid for the following keywords: magnetic resonance imaging, intrauterine devices, Implanon(®) and Essure(®). RESULTS: Though plastic devices do not represent a contraindication to the use of the technique, those including metallic components have been submitted to several tests, after which they were classified as MR Conditional (devices presenting no risks in MR-specific environments) by the Food and Drug Administration. Thus, the use of MRI can be safely advised to women with this type of device as long as the magnetic resonance equipment is ≤3.0 T. CONCLUSIONS: Presently, there is no scientific evidence that contraindicates performing MRI on women with any kind of gynecological device. Therefore, this procedure is safe as long as it is performed under previously tested conditions.

Gestational diabetes mellitus complicating twin pregnancies.

OBJECTIVE: To compare outcomes of twin pregnancies with and without gestational diabetes mellitus (GDM). STUDY DESIGN: We compared 105 twin pregnancies with GDM (7.8% of all twin pregnancies) to 315 controls without GDM, matched for gestational age, chorionicity and year of birth. RESULTS: Pre-gravid obesity appears to predispose women to GDM during twin pregnancy [odds ratio (OR) 3.5; 95% confidence interval (CI) 1.7, 7.0]. Overweight and obese women that subsequently developed GDM during their twin gestation were less likely to conceive spontaneously (OR 0.4; 95% CI 0.3, 0.7). Twins from the GDM group had more respiratory distress syndrome (RDS, OR 2.2; 95% CI 1.3, 3.7) and had a three-fold, but not significantly increased perinatal mortality rate. Birth weight characteristics were similar in both groups. CONCLUSION: Twin pregnancies complicated by GDM might be associated with pre-pregnancy maternal obesity and are at increased risk of RDS and non-significant increased risk of perinatal death.

Inovação na tela metálica utilizada no preparo de material para exame parasitológico de fezes através do método de sedimentação em copo / Inovation of the metallic sieve used in the preparation of samples for parasitological examination of feces by a cup sedimentation method

Em face do crescente custo da gaze em rolo, tipo queijo, usada na tarnisação da emulsão de fezes no método de sedimentação em copo, procurou-se uma alternativa que redundou numa volta ao passado - o uso de tela metálica em vez de gaze, tal como assinalou Adolfo Lutz, em 1919. Após uma série de experimentos com telas dotadas de diferentes números de malhas por polegada linear, selecionou-se a tela ideal que, retendo os detritos, permite a passagem de ovos e larvas de helmintos e cistos de protozoários. Essa tela possui 200 malhas por polegada linear e está adaptada a um aro de peneira, mediante técnica adequada; sendo de aço inoxidável e alumínio, é de duração prolongada, e de limpeza e manuseio fáceis. Foi efetuado estudo comparativo de 300 materiais fecais examinados após o método de sedimentação em copo, utilizando gaze e a peneira metálica acima relatada. Os dados obtidos patentearam a Superioridade da tela metálica, traduzi da por maior número de exames parasitológicos de fezes positivos, quer para ovos ou larvas de helmintos, quer para cistos de protozoários (AU).