Integrative proteomic profiling of ovarian cancer cell lines reveals precursor cell associated proteins and functional status.

A cell line representative of human high-grade serous ovarian cancer (HGSOC) should not only resemble its tumour of origin at the molecular level, but also demonstrate functional utility in pre-clinical investigations. Here, we report the integrated proteomic analysis of 26 ovarian cancer cell lines, HGSOC tumours, immortalized ovarian surface epithelial cells and fallopian tube epithelial cells via a single-run mass spectrometric workflow. The in-depth quantification of >10,000 proteins results in three distinct cell line categories: epithelial (group I), clear cell (group II) and mesenchymal (group III). We identify a 67-protein cell line signature, which separates our entire proteomic data set, as well as a confirmatory publicly available CPTAC/TCGA tumour proteome data set, into a predominantly epithelial and mesenchymal HGSOC tumour cluster. This proteomics-based epithelial/mesenchymal stratification of cell lines and human tumours indicates a possible origin of HGSOC either from the fallopian tube or from the ovarian surface epithelium.

Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis.

The cross-talk between ovarian cancer (OvCa) cells and the metastatic microenvironment is an essential determinant of successful colonization. MicroRNAs (miRNAs) have several critical roles during metastasis; however, the role of microenvironmental cues in the regulation of miRNAs in metastasizing cancer cells has not been studied. Using a three-dimensional culture model that mimics the human omentum, one of the principal sites of OvCa metastasis, we identified and characterized the microenvironment-induced downregulation of a tumor suppressor miRNA, miR-193b, in metastasizing OvCa cells. The direct interaction of the OvCa cells with mesothelial cells, which cover the surface of the omentum, caused a DNA methyltransferase 1-mediated decrease in the expression of miR-193b in the cancer cells. The reduction in miR-193b enabled the metastasizing cancer cells to invade and proliferate into human omental pieces ex vivo and into the omentum of a mouse xenograft model of OvCa metastasis. The functional effects of miR-193b were mediated, in large part, by the concomitant increased expression of its target, urokinase-type plasminogen activator, a known tumor-associated protease. These findings link paracrine signals from the microenvironment to the regulation of a key miRNA in cancer cells. Targeting miR-193b, which is essential for metastatic colonization of cancer cells could prove effective in the treatment of OvCa metastasis.

MicroRNAs 10a and 10b are potent inducers of neuroblastoma cell differentiation through targeting of nuclear receptor corepressor 2.

MicroRNAs function as negative regulators of posttranscriptional gene expression, having major roles in cellular differentiation. Several neuroblastoma cell lines can be induced to undergo differentiation by all-trans-retinoic acid (ATRA) and are used for modeling signaling pathways involved in this process. To identify miRNAs contributing to differentiation, we profiled 364 loci following ATRA treatment of neuroblastoma cell lines and found miR-10a and miR-10b to be highly overexpressed in SK-N-BE, LAN5 and SHSY-5Y. Ectopic overexpression of these miRNAs led to a major reprogramming of the transcriptome and a differentiated phenotype that was similar to that induced by ATRA in each of these cell lines. One of the predicted downregulated miR-10a/b targets was nuclear receptor corepressor 2 (NCOR2), a corepressor of gene transcription, which is known to suppress neurite outgrowth. NCOR2 was experimentally validated as a direct target of miR-10a/b, and siRNA-mediated inhibition of this mRNA alone resulted in neural cell differentiation. Moreover, induction of differentiation could be blocked by ectopic upregulation of NCOR2 using an expression construct lacking the miR-10a/b 3' untranslated region target site. We conclude that miR-10a/b has major roles in the process of neural cell differentiation through direct targeting of NCOR2, which in turn induces a cascade of primary and secondary transcriptional alterations, including the downregulation of MYCN.

Validation study of the s classification for melanoma patients with positive sentinel nodes: the Montreal experience.

BACKGROUND: Standard of care is to perform a complete lymph node dissection (CLND) in melanoma patients with positive sentinel lymph nodes (SLNs). However, less than 20% will have metastases in non-SLNs. The S classification was described to predict the non-SLN status, hoping to identify a subset of patients who can be spared the CLND. We tried to validate the feasibility and usefulness of this classification. MATERIALS AND METHODS: We performed a retrospective chart review. All melanoma cases between 1996 and 2006 were included, and 359 patients with SLN biopsies were identified. All pathology slides were reviewed with an emphasis on the S classification. RESULTS: There were 365 SLN biopsies performed. A total of 82 patients (22.8%) had positive SLNs, while 277 patients (77.2%) had negative SLNs. There were 22 patients classified as SI, 18 as SII, 37 as SIII, and 5 were unclassified. On CLND, only 10 patients (12.2%) had positive non-SLNs. None of these were classified as SI while 2 patients (11%) were classified as SII and 8 (22%) as SIII. The S category was found to be a predictor of non-SLN status, and this reached statistical significance (P = 0.044). On univariate analysis, only an increasing Breslow depth and ulceration were predictive of a non-SI status. CONCLUSION: Our results suggest that the S classification is easily feasible and predicts the status of non-SLNs. No patient with SI status was found to have additional non-SLN positive nodes. A larger-scale, prospective trial should be done to confirm these results and possibly spare patients the morbidity of CLND with a positive SLN.

Penetrating air gun wound in the neck.

BACKGROUND: Injuries from air weapons can be serious and potentially fatal. It has been estimated that up to four million such weapons exist in UK households. CASE REPORT: We present the case of an 8-year-old boy who sustained a penetrating neck wound from an air gun. Use of the flexible laryngoscope in the resuscitation room allowed localization of the gun pellet in the airway. CONCLUSIONS: This approach, combined with careful clinical assessment led to immediate removal by direct laryngoscopy, thus avoiding the morbidity of unnecessary surgical exploration.

Cost and morbidity of MRSA in head and neck cancer patients: what are the consequences?

Methicillin resistant Staphylococcus aureus (MRSA) has become a prevalent nosocomial pathogen worldwide. The objectives of this study were to assess the morbidity and cost associated with the treatment of head and neck cancer patients who become colonized or infected with MRSA following major surgical procedures. We present a retrospective review of patients who underwent major surgery for head and neck cancer over a one year period and who then became MRSA positive in the post-operative period. MRSA affected 25/55 (45 per cent) patients who underwent major head and neck procedures during the period studied. The mean time of diagnosis was 13 days post-surgery. Morbidity included cellulitis, osteomyelitis and MRSA pneumonia. Thirteen of the patients who became MRSA positive (52 per cent of the MRSA group) required further surgery including plate removal, new flap formation and wound debridement as a result of the infection. Average in-hospital stay was almost three times more prolonged for patients who became MRSA positive compared to those who did not have MRSA. The costs of the first hospital stay were over three times more in the MRSA-positive group of patients. Antibiotic costs were increased by pound 2470 per patient because of MRSA. The extra stay in hospital, together with extra days in intensive care, extra medical and nursing care and additional costly antibiotic treatment, led to major cost implications and loss of health service resources in the unit. MRSA infection is a serious cause of morbidity in any surgical group of patients and this study focuses on the consequences for treatment of head and neck cancer patients in particular.

Massive subcutaneous emphysema following routine endotracheal intubation.

Upper aerodigestive tract injury after endotracheal intubation is a rare but serious complication. The case of a 57-year-old female, who developed extensive neck and pneumomediastinum following a knee arthroscopy under general anaesthesia, is presented. Possible mechanisms of injury and management options are discussed.

Management of a large bronchial haemangioma in an infant.

Haemangiomas are the most common soft tissue tumor of infancy. Despite the benign and trivial nature of most cutaneous haemangiomas, airway haemangiomas are rare but potentially life threatening. We report the case of a 9-week-old infant with a left main stem bronchial haemangioma. This was successfully treated with the oral corticosteroids. We discuss the current available treatments for haemangiomas and highlight that treatment should be specific to each individual case.

Translevator anal anomalies with cutaneous fistulae passing deep to the scrotum.

METHODS: The authors present a series of 9 patients collected from 4 centers with translevator anal anomalies, each of which has a fistula tracking forward deep to the scrotum and opening at the peno-scrotal junction. Whereas some would appear to be covered ani in type, others are deeper and would appear to fit in with an intermediate type of classification emphasizing the idea of a "spectrum" of malformation. RESULTS: The anatomic arrangement, associated anomalies (eg, 2 had hypospadias), and surgical management is described briefly in each case. Careful examination may be necessary to identify the fistula. CONCLUSIONS: It is recommended that the surgery be individualized depending on the findings. On a theoretical embryologic basis there is abnormality in the formation of the outer genital folds, and there also may be abnormality in some cases of the inner genital folds.

A holistic approach to meeting students' needs: using hypnotherapy techniques to assist students in managing their health.

Nursing education has long been holistic in its approach to aiding the client or family. Further, most nurses, especially school nurses, are holistic by nature. That is, school nurses see a person as a whole being, physical, emotional, mental, and spiritual. The more conscious nurses become of their holistic nature and the more they expand their knowledge and skills in holistic methods, the more they can assist students and families in having greater control over their health. Examples of selected holistic techniques and their positive effects when used by students with diabetes and asthma are illustrated in case studies.

The current family planning debate in Soviet Central Asia.

PIP: This paper reviews the debate that occurred in the press of the Soviet Central Asian republics during 1988 and 1989 on the issue of family planning. The author identifies three basic opinion groups, those in favor of family planning, those in favor of family planning with certain reservations, and those opposed to family planning. The role this debate has played in bringing into the open a number of political, cultural, economic, and social issues, together with data to support the positions taken that are now possible with glasnost, is noted.^ieng

Reduction of glycemic and lipid levels in db/db diabetic mice by psyllium plant fiber.

The soluble plant fiber psyllium significantly reduced fasting glucose and total cholesterol levels in the C57BL/KsJ db/db diabetic mouse relative to placebo-fed mice. Insulin levels were significantly higher in psyllium-fed than placebo-fed animals, indicating this fiber may delay the progression of diabetes in the animal model. High-density lipoprotein cholesterol levels rose moderately in both psyllium- and placebo-fed animals during the study, whereas triglyceride levels remained unchanged in both groups. Psyllium's effect on glycemic, lipid, and hormone parameters was not explained by weight loss or reduced food intake; these were similar in psyllium- and placebo-fed animals during the study. Our results show that psyllium fiber can beneficially moderate glycemic and lipid parameters in the db/db diabetes model.

Congenital leukonychia striata.

Leukonychia striata of a unique appearance and distribution is described in a 51-year-old woman. Histopathologic examination of a specimen from the nail plate revealed a transverse band of parakeratosis on the ventral surface. Disturbance in keratinization on the nail plate is presumed to be secondary to abnormalities in the nail matrix. We review briefly the classification and pathogenesis of leukonychia, an interesting aberration in nail plate keratinization.