Benign endocervical cystic glandular change mimicking minimal deviation adenocarcinoma of the cervix on magnetic resonance imaging: a case report.
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Adenocarcinoma↗
Biomedical subjects
Michael Quinn
Publications and source records attributed to Michael Quinn.
Embodied changes and the search for gynecological cancer diagnosis.
The detection and successful treatment of cancers is dependent on timely presentation with abnormal and often subtle symptoms. In this article, we draw on research conducted with Australian immigrant women in 2001-02 who experienced delays in diagnosis of gynecological cancer. Data from in-depth interviews with women with gynecological cancer indicated a common trajectory of an "illness career" whereby the search for diagnosis was often painful and lengthy, either because women normalized the abnormal signs or because their experiences of bodily abnormality, pain, and dysfunction contrasted with medical explanations. This delay was sometimes exacerbated by structural barriers. As a result, diagnosis was often protracted, during which time women presented with symptoms that were dismissed or resulted in the misdiagnosis, with a resultant loss of confidence in clinical services.
Aged↗
An approach to remove albumin for the proteomic analysis of low abundance biomarkers in human serum.
Proteomic technologies are being used to discover and identify disease-associated biomarkers. The application of these technologies in the search for potential diagnostic/prognostic biomarkers in the serum of patients has been limited by the presence of highly abundant albumin and immunoglobulins that constitute approximately 60-97% of the total serum proteins. The purpose of the study was to evaluate whether treatment of human serum with Affi-Gel Blue alone or in combination with Protein A (Aurum serum protein mini kit, Bio-Rad) before two-dimensional gel electrophoresis (2-DE) analysis removed high abundance proteins to allow the visualization of low abundant proteins. Serum samples were treated with either Affi-Gel Blue or Aurum kit and then subjected to 2-DE using 11 cm, pH 4-7 isoelectric focussing strips for the first dimension and 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis for second dimension. Protein spots were visualized using a fluorescent protein dye (SYPRO Ruby, Bio-Rad). Comparison between treatment methods showed significant removal of albumin by both Affi-Gel Blue and Aurum kit and considerable differences in the protein profile of the gels after each treatment. Direct comparison between treatments revealed twenty-eight protein spots unique to Affi-Gel Blue while only two spots were unique after Aurum kit treatment. Unique spots in Affi-Gel Blue and Aurum kit treated serum were not visualized in untreated serum. Sixteen hours of Affi-Gel Blue treatment resulted in enhanced visualization of fifty-three protein spots by two-fold, thirty-one by five-fold, twelve by ten-fold and six by twenty-fold. In parallel after Aurum kit treatment two-, five-, ten- and twenty-fold enhancements of thirty, thirteen, eight and five protein spots, respectively, were observed. The pattern of increased visualization of protein spots with both treatment methods was similar. In conclusion, treatment of serum samples with Affi-Gel Blue or Aurum kit before 2-DE analysis can be used to remove high abundance proteins in order to increase the detection sensitivity of proteins present in low abundance.
Biomarkers↗
Proteomic profiling of proteins associated with urokinase plasminogen activator receptor in a colon cancer cell line using an antisense approach.
Expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) strongly correlates with a malignant tumour cell phenotype. In the multistep process of metastasis, uPA binding to uPAR influences different cellular functions. In the present study, a highly metastatic colon cancer cell line, HCT116 was transfected with an expression vector containing a 5' uPAR cDNA fragment in an antisense orientation. This construct was most effective in reducing uPAR cell surface expression as confirmed by flow cytometry analysis. Antisense transfection of HCT116 cells had no effect on proliferation but the following effects were observed: (1) a 1.3-fold decreased adhesion; (2) a two-fold decreased Erk MAP kinase activity; (3) a 2.7-fold decrease in Src kinase activity; (4) a 1.5- and two-fold decrease in uPA cell surface expression and secretion; (5) abrogation of promatrix metalloproteinase-9 secretion; and (6) a complete suppression of plasminogen-dependent matrix degradation. Using proteomic analysis, we demonstrate loss of approximately 200 proteins and quantitative differences in the expression of 141 other proteins in an antisense-clone compared to wild-type and mock-transfected control. Such changes in protein expression with the down-regulation of uPAR may be an important contributor in colon cancer progression and metastasis and may not only provide a basis to develop a proteomic data bank of uPAR-mediated signaling molecules but may also lead to the development of therapeutic approaches for the cure and better management of colon cancer.
5' Untranslated Regions↗
Alopecia neoplastica caused by desmoplastic melanoma.
A 50-year-old man presented with a 6-month history of localized alopecia on the left frontal area of the scalp. Biopsy revealed desmoplastic melanoma with associated neurotropism. Wide excision was performed and showed desmoplastic melanoma extending to excision margins. Hair follicles were focally reduced in number and were infiltrated by melanoma cells. He has subsequently required multiple wide excisions, exenteration of the left eye and radiotherapy. He has had multiple recurrences and has developed involvement of the first division of the trigeminal nerve intracranially. To the authors' knowledge, this is the first reported case of desmoplastic melanoma presenting as alopecia.
Alopecia Areata↗
Incidence of microsatellite instability in synchronous tumors of the ovary and endometrium.
PURPOSE: Families with hereditary nonpolyposis colorectal cancer (HNPCC) have an increased lifetime risk of endometrial (40%) and ovarian (10%) carcinomas. Endometrial and ovarian carcinomas from members of these families frequently display a mutator phenotype as manifest by high levels of microsatellite instability (MSI-H). Microsatellite instability (MSI) occurs in 17-32% of sporadic endometrial carcinomas and 3-17% of sporadic ovarian carcinomas. We hypothesized that there might be a higher rate of MSI in tumors from women with synchronous primary carcinomas of the ovary and endometrium. EXPERIMENTAL DESIGN: We identified 52 cases of synchronous tumors of the ovary and endometrium from the databases of four gynecological oncology units. Archival material and clinical data were available on 45 of these patients. We examined DNA extracted from ovarian and endometrial tumor tissue for MSI using DNA extracted from normal tissue of that patient as a germ-line DNA control. MSI was assessed using a panel of five standard microsatellite markers: D2S123, D5S346, D17S250, BAT25, and BAT26. MSI-H was defined by more than two markers being positive. Low-level MSI (MSI-L) was defined as one or two markers positive and microsatellite stable (MSS) was defined as no markers positive. RESULTS: The 45 patients had a median age at diagnosis of 53 years. Of a total of 134 samples analyzed, only three samples (3.3%) were MSI-H. No patient had high levels of MSI in both ovarian and endometrial tumors. One ovarian carcinoma had five of five markers positive with the corresponding endometrial carcinoma being MSI-L. Two endometrial carcinomas were MSI-H, and the corresponding ovarian carcinomas were MSI-L and MSS, respectively. Seven ovarian tumors and seven endometrial tumors were MSI-L. The majority of patients had early-stage ovarian carcinoma [International Federation of Gynecology and Obstetrics (FIGO) stage I, 44.4%; stage II, 26.7%; and stage III, 26.6%]. Eighty-two % of the endometrial primaries were FIGO stage I. Progression-free survival was significantly better for patients with synchronous primaries than those presenting with ovarian carcinoma alone [adjusted hazards ratio, 1.94; P = 0.023; 95% confidence interval, 1.096-3.44]. CONCLUSION: Synchronous primary carcinomas of the ovary and endometrium are unlikely to be part of the HNPCC syndrome unless the family history is in keeping with the modified Amsterdam criteria.
Colorectal Neoplasms, Hereditary Nonpolyposis↗
Cotyledonoid dissecting leiomyoma.
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CA-125 Antigen↗
Association between alphavbeta6 integrin expression, elevated p42/44 kDa MAPK, and plasminogen-dependent matrix degradation in ovarian cancer.
Altered expression of alphav integrins plays a critical role in tumor growth, invasion, and metastasis. In this study, we show that normal human epithelial ovarian cell line, HOSE, and ovarian cancer cell lines, OVCA 429, OVCA 433, and OVHS-1, expressed alphav integrin and associated beta1, beta3, and beta5 subunits, but only ovarian cancer cell lines OVCA 429 and OVCA 433 expressed alphavbeta6 integrin. The expression of alphavbeta6 in OVCA 429 and OVCA 433 was far higher than alphavbeta3 and alphavbeta5 integrin and correlated with high p42/p44 mitogen activated protein kinase (MAPK) activity and high secretion of high molecular weight urokinase plasminogen activator (HMW-uPA), pro-metalloproteinase 2 and 9 (pro-MMP-9 and pro-MMP-2). In contrast to HOSE and OVHS 1, OVCA 433 and OVCA 429 exhibited approximately 2-fold more plasminogen-dependent [3H]-collagen type IV degradation. Plasminogen-dependent [3H]-collagen IV degradation was inhibited by inhibitor of uPA (amiloride) and MMP (phenanthroline) and by antibodies against uPA or MMP-9 or alphavbeta6 integrin, indicating the involvement of alphavbeta6 integrin, uPA and MMP-9 in the process. The alphavbeta6 correlated increase in HMW-uPA and pro-MMP secretion could be inhibited by tyrosine kinase inhibitor genistein or the MEK 1 inhibitor U0126, consistent with a role of active p42/44 MAPK in the elevation of uPA, MMP-9, and MMP-2 secretion. Under similar conditions, genistein and U0126 inhibited plasminogen-dependent [3H]-collagen type IV degradation. These data suggest that sustained elevation of p42/44 MAPK activity may be required for the co-expression of alphavbeta6 integrin, which in turn may regulate the malignant potential of ovarian cancer cells via proteolytic mechanisms.
Antigens, Neoplasm↗
Conventional approach to glucose management for diabetic patients undergoing coronary artery bypass surgery.
Continuous insulin infusion was not an effective mode of treatment in maintaining safe blood glucose levels (<200 mg/dl) during the intraoperative period of diabetic patients requiring open-heart surgery. The two modifications investigated to gain better control of the blood glucose were a change in the base solution of the cardioplegia and the use of a sliding insulin scale. Fifty patients including Type I and Type II diabetics were selected for the purpose of this study. The patients were then randomly divided into two groups categorized by the type of cardioplegic solution administered and the mode of insulin treatment. Group I patients received a dextrose 5%-based cardioplegic solution and blood glucose was treated via continuous intravenous insulin infusion. Group II patients received normal saline 0.9%-based cardioplegic solution and blood glucose was treated via sliding scale. Blood glucose levels were monitored pre- and postcardiopulmonary bypass (CPB) and every 30 min while on CPB. Glucose values were analyzed by group t test. A p value of <0.05 was considered statistically significant. When comparing Group I (mean=258 mg/dl) with Group II (mean=158 mg/dl), there was a statistically significant difference between the glucose values at each of the time intervals when the glucose values were recorded. In conclusion, Group II maintained an acceptable blood glucose level (<200 mg/dl) throughout the entire intraoperative period, which suggests that the combination of the sliding insulin scale and modification of the base cardioplegic solution was an effective mode of treatment.
Aged↗
Screening the high risk patient for gynaecological cancer.
It is often difficult to conclude that improvements in survival with time are due to a screening programme alone. Although a reduction in the death rate from a given cancer may reflect the benefits of early detection or improved treatment, the benefits may also result from lead time bias and over-diagnosis, the former resulting in longer survival of screen-identified cancers because the time before the cancer would have been clinically diagnosed is included in calculations. Furthermore, recent reviews on randomised clinical trials of cancer screening have provided strong evidence that misclassifications in causes of death have been a major problem, leading to an over-estimation of the effectiveness (or alternatively an under-estimation of potential harm) of screening.
Endometrial Neoplasms↗
Reproductive consequences of EDCs in birds: what do laboratory effects mean in field species?
The varied reproductive strategies of birds present a challenge in developing reliable indices for the assessment of effects of endocrine disrupting chemicals (EDCs). Precocial species, such as quail, appear to be most sensitive to EDC effects during embryonic development. Although the Japanese quail (Coturnix japonica) is a nonnative lab species, its reproductive strategy is similar to that of many free-ranging species. Because a great deal is known about the reproductive biology of this species and Japanese quail have a short generation time, this species is an ideal candidate for testing EDC effects. In this review, we present data collected in a two-generation design with embryonic exposure to estradiol benzoate (EB). This study was conducted to provide fundamental information for establishing reliable reproductive endpoints associated with estrogenic EDC exposure. Data were collected for a variety of endpoints, which were chosen as measures of reproductive capability and success. These reproductive fitness measures included fertility, hatching success, and offspring viability. Endocrine measures consisted of plasma hormone levels and gonad weight/condition. Neuroendocrine systems, such as the monoamine neurotransmitter systems, regulate hypothalamic gonadotropin releasing hormone (GnRH) and reproductive behavior. Therefore, these variables should potentially be very sensitive indicators. Behavioral measures included reproductive behavior. Results showed that embryonic estradiol exposure affected endocrine and behavioral responses in males and impacted productivity in females. Therefore, quails provide an excellent model to determine fundamental actions of EDCs. The laboratory trials then serve as a basis for the extrapolation of findings of controlled laboratory studies to effects that may be observable in free-ranging species.
Animals↗