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PURPOSE: Overall survival (OS) is the primary end point in phase III oncology trials. Given low success rates, surrogate end points, such as progression-free survival or objective response rate, are used in early go/no-go decision making. Here, we investigate whether early trends of OS prognostic biomarkers, such as the ROPRO and DeepROPRO, can also be used for this purpose. METHODS: Using real-world data, we emulated a series of 12 advanced non-small-cell lung cancer (aNSCLC) clinical trials, originally conducted by six different sponsors and evaluated four different mechanisms, in a total of 19,920 individuals. We evaluated early trends (until 6 months) of the OS biomarker alongside early OS within the joint model (JM) framework. Study-level estimates of early OS and ROPRO trends were correlated against the actual final OS hazard ratios (HRs). RESULTS: We observed a strong correlation between the JM estimates and final OS HR at 3 months (adjusted R2 = 0.88) and at 6 months (adjusted R2 = 0.85). In the leave-one-out analysis, there was a low overall prediction error of the OS HR at both 3 months (root-mean-square error [RMSE] = 0.11) and 6 months (RMSE = 0.12). In addition, at 3 months, the absolute prediction error of the OS HR was lower than 0.05 for three trials. CONCLUSION: We describe a pipeline to predict trial OS HRs using emulated aNSCLC studies and their early OS and OS biomarker trends. The method has the potential to accelerate and improve decision making in drug development.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Prognosis , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Disease-Free Survival , BiomarkersABSTRACT
PURPOSE: Galectins are carbohydrate-binding proteins with multiple effects on cell biology. Research shows that they play an important role in tumor development and progression. Therefore, in this study, the presence of Galectin-8 and -9 (Gal), both already known as prognostic factors in other tumor entities, were investigated in cervical cancer. Our aim was to examine the association of Gal-8 and -9 expression with histopathological markers and survival of the patients. METHODS: Gal-8 and -9 expression was investigated in 250 cervical cancer samples by immunohistochemistry. The staining was evaluated using the immunoreactive score (IRS). The results were correlated to clinical and pathological data. The correlation of Gal-8 and -9 expression with overall and relapse-free survival was analyzed. RESULTS: Expression of Gal-8 was associated with negative N-status and lower FIGO status. Detection of Gal-9 was connected to negative N-status and lower grading regarding all specimens. A correlation of Gal-9 with lower FIGO status was detected for squamous cell carcinoma (SCC) only. Expression of Gal-8 was associated with relapse-free survival of SCC patients in a positive manner. Gal-9 expression was associated with better overall survival. CONCLUSION: Our results suggest that expression of both galectins is inversely associated with tumor stage and progression. Gal-8 expression is associated with relapse-free survival of patients with SCC, while presence of Gal-9 in cervical cancer is associated with a better prognosis in regard of overall survival.
Subject(s)
Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Carcinoma, Squamous Cell/pathology , Female , Galectins , Humans , Immunohistochemistry , Neoplasm Recurrence, Local , Prognosis , Uterine Cervical Neoplasms/pathologyABSTRACT
OBJECTIVE: Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. STUDY DESIGN: 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting RESULTS: A correlation of nuclear Sirt1 and RXRα expression could be detected (p = 0.006). Co-expression of nuclear RXRα and cytoplasmic (p = 0.026) or nuclear (p = 0.041) Sirt1 was associated with significantly increased overall survival in advanced tumour stages. Viability was decreased in all cell lines after stimulation with resveratrol, while cell apoptosis was increased. RSV treatment led to significant lower Sirt1 expression in A2780 cells (p = 0.025) and significant increased RXR expression in cisA2780 cells (p = 0.012) CONCLUSION: In order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.
Subject(s)
Ovarian Neoplasms , Resveratrol , Retinoid X Receptor alpha , Sirtuin 1 , Cell Line, Tumor , Female , Humans , Ovarian Neoplasms/drug therapy , Prognosis , Resveratrol/pharmacology , Retinoid X Receptor alpha/genetics , Sirtuin 1/geneticsABSTRACT
INTRODUCTION: Breast cancer (BC) is the most common cancer in women worldwide. Despite screening and information efforts, about 10% of patients present with tumor size T3 or T4 at primary diagnosis. Late presentation is associated with more advanced tumor stage and consecutively with worse survival rates. OBJECTIVE: This study aimed to evaluate whether patients with a late presentation at primary BC diagnosis differ in their personality from those with early diagnosis. METHODS: In this bicentric, observational study, personality traits, positive and negative affectivity, anxiety, spirituality, illness beliefs, and sociodemographic characteristics were assessed in BC patients who presented with T-stages 3 or 4 (late presenters) and T-stages 1 or 2 (controls) at initial diagnosis. RESULTS: Forty patients (20 controls, 20 late presenters) were interviewed. "Late presenters" perceived their disease as long lasting and had significantly more "positive affectivity" in the current trait. Although no significant associations were found, there was a trend for late presenters to have higher education levels, less spiritual longing, less accurate explanation of their illness, less anxiety in the trait scale, and more conscientiousness than the controls. CONCLUSION: As patients with late presentation for BC differ in specific psychological and sociodemographic characteristics from patients with early BC, the findings of this pilot project warrant additional investigations to identify further specific characteristics and motivations. Identifying patients at risk for late presentation and encouraging them to accept an earlier diagnosis could help to improve their therapy and, finally, their outcome.
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BACKGROUND: Maternal immunological rejection of the semi-allogenic fetus is discussed as one of the significant factors involved in early pregnancy loss. An array of cytokines secreted by both maternal and fetal cells is involved in generating a delicate maternal immune tolerance. Interleukin-7 (IL-7) is discussed to play a key role in pro-inflammatory processes, but there is still limited insight into the pathophysiological input on placentation and embryonic development in early pregnancy loss. PATIENTS AND METHODS: Cytokine level differences were identified with quantitative real-time PCR in placental tissue from spontaneous abortions (SA) (n = 18), recurrent spontaneous abortions (RSA) (n = 15), and healthy pregnancies (n = 15) at gestational weeks 7 to 14. Protein expression of IL-7 in the decidua was investigated by immunohistochemistry. IL-7-expressing cells were identified with double-immunofluorescence. RESULTS: Decidua of women with RSA expressed almost 51-times higher values of IL-7 in gene expression analysis. Immunohistochemistry identified a significant upregulation of IL-7 in the decidua of RSA specimens (p = .013) and in the decidua of women with SA (p = .004). Double-immunofluorescence confirmed decidual stroma cells as IL-7-expressing cells. CONCLUSION: Significantly elevated IL-7 values in the decidua of spontaneous and recurrent miscarriages imply a crucial role of the cytokine in the signaling at the feto-maternal interface of the placenta. An overexpression of IL-7 could result in early pregnancy loss by inducing a pro-inflammatory environment. Proven to be valuable in other autoimmune diseases, targeting IL-7 signaling therapeutically may prove to be a very beneficial treatment option for RSA patients.
Subject(s)
Abortion, Spontaneous/immunology , Decidua/immunology , Interleukin-7/immunology , Adult , Female , Humans , Interleukin-7/metabolism , Pregnancy , Up-RegulationABSTRACT
PURPOSE: Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (MBC) is an important consideration for subsequent use in clinical practice. Unfortunately, such subgroup analyses often are exploratory and rarely statistically adequately powered and may thus be misleading. This analysis aimed to explore a potentially different treatment response to i.v. therapies between visceral and non-visceral MBC. METHODS: In a systematic literature analysis (PubMed) comprising phase III registration studies for MBC from 1994 to 2014, differences in outcome were evaluated regarding progression-free survival, time to progression, overall survival (OS), and visceral versus non-visceral disease. The impact of HER2 and hormone receptor status was also considered. A total of 16 studies comprising 13,083 patients were selected by considering the information given in the medical product's professional information and the decision of the US Food and Drug Administration or the European Medicine Agency for approval of the respective therapeutic agents now used in the treatment of MBC. RESULTS: No statistically significant differences regarding treatment response and therapy benefit were found in MBC patients with visceral versus non-visceral metastases based on reported hazard ratios and confidence intervals in registration trials. Interesting but nonsignificant differences were found regarding a distinct therapy benefit regarding different metastasis locations in 4 studies. CONCLUSION: For targeted i.v. therapies based on biomarker selection, there is a trend - although not significant - toward a benefit (OS) from combination therapies favoring visceral disease. However, at the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in MBC.
ABSTRACT
Gestational diabetes mellitus (GDM) is known to increase the risk for feto-maternal complications during pregnancy. A state of low-grade inflammation, with elevated levels of proinflammatory molecules, similar to patients with obesity or diabetes mellitus type 2 has also been partly described in GDM. The placenta, as unique interface between mother and fetus, is not only passively affected by changes in one of these organisms, but also acts as a modulator by expressing hormones and cytokines. This study aimed to investigate the expression of the proinflammatory cytokines Interleukin (IL) 7, 8 and 15 in GDM in placental tissue. A total number of 80 placentas were included (40 GDM/40 control group). The expression of IL-7, 8 and 15 was investigated in extravillous trophoblast (EVT) and syncytiotrophoblast (SCT) by immunohistochemistry and immunofluorescence double staining. The immunohistochemical staining was evaluated with the semiquanitfied immunoreactive score (IRS). While the expression IL-15 was significantly upregulated in EVTs of women with GDM. The expression of IL-8 was significantly decreased in EVT of the GDM group. Furthermore, significant fetal sex specific differences were detectable in all three cytokines. Our findings suggest an involvement of the investigated cytokines in the maintenance of a state of chronic low-grade inflammation on placental level in patients suffering from GDM.
Subject(s)
Diabetes, Gestational/metabolism , Interleukin-15/metabolism , Interleukin-7/metabolism , Interleukin-8/metabolism , Placenta/metabolism , Trophoblasts/metabolism , Diabetes, Gestational/pathology , Female , Humans , Male , Pregnancy , Sex FactorsABSTRACT
Several risk factors like obesity and hyperlipidemia were described for endometrial cancer. Here, the nuclear NAD-dependent histone-deacetylase Sirtuin1 (SIRT1) seems to be important. SIRT1 is also involved in cell regulatory mechanisms and can serve as tumor promotor or suppressor. Its role in tumor biology is not clear yet. In this study, we evaluated and correlated the SIRT1 expression with patients' tumor characteristics in endometrioid and clear-cell cancer of the uterus. 65 paraffin-embedded samples of patients with endometrial and clear-cell cancer of the uterus were immunohistochemically stained and SIRT1 expression was evaluated by immunoreactive score. The results were correlated to clinical and pathological tumor characteristics as well as to the expression of ARID1A and ß-Catenin. The staining was significantly more intensive in uterine endometrioid carcinoma compared to uterine clear-cell carcinoma (p = 0.007). The expression of SIRT1 correlated significantly with the membranous expression of ß-Catenin (p = 0.028) and ARID1A (p = 0.021). Patients with positive Sirtuin1 expression had a significantly better progression-free survival (p = 0.042), the overall survival showed a trend towards a better prognosis (p = 0.070). SIRT1 expression seems to be associated with improved progression-free survival in uterine cancer (endometrioid and clear-cell) and is correlated to the tumor suppressors ß-Catenin and ARID1A. Further studies are necessary to elucidate the role of SIRT1 in uterine and ovarian cancer and its potential as a therapeutic target.
Subject(s)
Adenocarcinoma, Clear Cell/metabolism , Endometrial Neoplasms/metabolism , Sirtuin 1/biosynthesis , Uterine Neoplasms/metabolism , Adenocarcinoma, Clear Cell/pathology , Aged , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Survival Analysis , Uterine Neoplasms/pathologyABSTRACT
PURPOSE: Breast cancer is the leading cause of cancer death in females. Histone modifications have been shown to have an influence on the gene expression. This study focusses on the histone modifications H3K9ac and H3K4me3 in breast cancer and their impact on survival METHODS: H3K4me3 and H3K9ac expression was immunohistochemically examined in 235 tissue samples. RESULTS: Positive estrogen receptor status was correlated with a higher IRS of the nuclear (p = 0.033), and of the cytoplasmic H3K4me3 staining (p = 0.009). H3K9ac intensity was associated to the Her2 status (p = 0.045) and to poor prognosis in cells with positive Ki67 status (p = 0.013). A high intensity of nuclear H3K4me3 staining was found to be correlated with a lower 10-year-survival (p = 0.026) and with lower breast cancer-specific survival (p = 0.004). High percentage score (> 190) of H3K9ac expression was correlated to worse breast cancer-specific survival (p = 0.005). Shorter progression-free survival was found in patients with nuclear (p = 0.013) and cytoplasmic H3K4me3expression (p = 0.024) and H3K9ac expression (p = 0.023). CONCLUSION: This analysis provides new evidence of histone modifications in breast cancer. High H3K4me3 and H3K9ac expression was correlated with survival rates. Further investigation of histone modifications in breast cancer could lead to a more profound understanding of the molecular mechanisms of cancer development and could result in new therapeutic strategies.
Subject(s)
Breast Neoplasms/metabolism , Histones/biosynthesis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Female , Gene Expression , Histones/genetics , Histones/metabolism , Humans , Immunohistochemistry , Middle Aged , Progression-Free Survival , Survival RateABSTRACT
Breast cancer (BC) is the most frequent cancer in women and the leading cause of cancer death in females worldwide. Rapid research advancements add to the complexity of treatment options for this disease. It is known that the quality of patients' care is deeply affected by healthcare professionals following these advancements. There is a growing need for academic education to increase clinical knowledge and skills of physicians treating BC patients. The certificate of Competence in Breast Cancer Program (CCB) is a Certificate in Advanced Studies (CAS) organized by the European School of Oncology in cooperation with Ulm University (Germany), which focuses on both the clinical and scientific competence required for improving quality in the management of BC patients. This paper describes the experience of the second CCB cohort (CCB2), which brought together 24 physicians from four continents who shared the common will to improve their competence and skills in BC treatment.
Subject(s)
Breast Neoplasms/therapy , Clinical Competence , Medical Oncology/education , Specialization , Adult , Certification , Curriculum , Female , Humans , Male , Pathology, Clinical/education , Radiology/educationABSTRACT
OBJECTIVES: Arteritic anterior ischemic optic neuropathy (A-AION) caused by inflammatory occlusion of the posterior ciliary arteries is the most common reason for irreversible vision loss in patients with giant cell arteritis. Atypical clinical presentation and negative funduscopy can delay systemic high-dose corticosteroid therapy to prevent impending permanent blindness and involvement of the contralateral eye.The purpose of this study was to assess the diagnostic accuracy of 3-dimensional (3D) high-resolution T1-weighted black-blood magnetic resonance imaging (T1-BB-MRI) for the detection of posterior ciliary artery involvement in patients with giant cell arteritis and funduscopic A-AION. MATERIALS AND METHODS: After institutional review board approval and informed consent, 27 patients with suspected giant cell arteritis and vision disturbances were included in this monocentric prospective cohort study. Giant cell arteritis was diagnosed in 18 patients according to the diagnostic reference standard (6 men, 73.8 [69.0-78.0] years); 14 of those were positive for A-AION. Precontrast and postcontrast 3D T1-BB-MRI was performed in all 27 patients. Two radiologists separately assessed image quality and local fat suppression (4-point scale), visual contrast enhancement (3-point scale), and diagnostic confidence (5-point scale) regarding arteritic posterior ciliary artery involvement. Magnetic resonance imaging findings were assessed in comparison to funduscopy. Statistical analysis included accuracy parameters and interrater agreement. RESULTS: Sensitivity of 3D T1-BB-MRI was 92.9% (95% confidence interval, 66.1%-99.8%) and specificity was 92.3% (95% confidence interval, 64.0%-99.8%) for detection of A-AION-positive patients. Image quality and local fat suppression were assessed with 3.2 ± 0.8 (median 3) and 3.8 ± 0.5 (median 4). Visual contrast enhancement with 2.3 ± 0.8 (median 3) and diagnostic confidence was rated at 4.7 ± 0.5 (median 5). Interrater agreement was high (κ = 0.85, P < 0.001). Three-dimensional T1-BB-MRI displayed bilateral findings in 50% of the cases, whereas only unilateral A-AION was detected in funduscopy as a possible indication for the contralateral eye at risk. CONCLUSIONS: Three-dimensional T1-BB-MRI allows accurate detection of arteritic posterior ciliary artery involvement in patients with A-AION. Further, 3D T1-BB-MRI seems to display arteritic involvement of the posterior ciliary arteries earlier than funduscopy and might, therefore, display "vision-at-risk" in patients with visual impairment and suspected giant cell arteritis but unremarkable funduscopy.
Subject(s)
Giant Cell Arteritis/complications , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Optic Neuropathy, Ischemic/complications , Optic Neuropathy, Ischemic/diagnostic imaging , Aged , Cohort Studies , Female , Humans , Magnetic Resonance Angiography , Male , Optic Nerve/diagnostic imaging , Prospective Studies , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
PURPOSE: The purpose of this study was the evaluation of risk factors for local recurrence after breast conserving surgery (BCS) with special focus on the impact of residual disease in specimens of simultaneous additional excisions (AE) from the tumor cavity on patients' outcome in patients with negative final margin status after one-step BCS. METHODS: This study was designed as a single center retrospective cohort study. Patients with primary non-metastatic breast cancer treated by one-step BCS with pathologically confirmed negative resection status between 1990 and 2006 were included. Ipsilateral breast tumor recurrence (IBTR) and overall survival (OS) were evaluated by Kaplan-Meier-estimates. A multivariate Cox proportional hazards regression model was used to identify potential independent prognostic factors associated with the risk of IBTR. RESULTS: A total of 1081 patients were included in this analysis. Simultaneous additional excisions were performed in 79.4% of patients (tumor positive: 12.2%). Median follow-up after primary diagnosis was 124 months. The IBTR rate after 15 years was significantly higher in the group with tumor positive AE (no AE (10.2%) vs. AE tumor positive (27.5%) p = 0.002; AE tumor negative (14.0%) vs. AE tumor positive (27.5%) p = 0.008). The OS rate did not differ significantly between groups. Multivariate analysis revealed residual cancer in AE being associated with a significantly increased relative risk of IBTR of 2.0 (p = 0.014). CONCLUSION: In the current analysis residual disease in simultaneous additional excisions was associated with an increased risk for IBTR despite negative final margin status. This should be considered in the overall therapeutic concept.
Subject(s)
Breast Neoplasms/surgery , Mastectomy, Segmental/methods , Neoplasm Staging , Neoplasm, Residual/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Margins of Excision , Middle Aged , Prognosis , Retrospective Studies , Survival Rate/trendsABSTRACT
PURPOSE: The Fas-antigen is a cell surface receptor that transduces apoptotic signals into cells. The purpose of this study was to evaluate FasL expression in breast cancer and to elucidate the role of its signaling in different breast cancer cell lines. METHODS: T47D and MCF7 cells were used and cultured in Dulbecco's modified Eagle's medium. FasL translocation to the membrane was achieved by culturing the cells in the presence of human interferon-γ (IFNγ). Translocation was detected by immunofluorescence. The ability of a Fas:Fc fusion protein to trigger apoptosis in these cells was investigated by cell death detection ELISA. After incubation with IFNγ for 4 h and 18 h, apoptosis was assessed in response to treatment with Fas:Fc. RESULTS: Immunofluorescence revealed that the used cell lines were positive for FasL which was increased and changed to more membrane-bound FasL expression after IFNγ stimulation. After stimulation with 50 IU/ml IFNγ, Fas:Fc significantly increased MCF7 apoptosis (1.39 ± 0.06-fold, p = 0.0004) after 18 h. After stimulation with 100 IU/ml, Fas:Fc significantly increased apoptosis both after 4 h (1.49 ± 0.15-fold, p = 0.018) and 18 h (1.30 ± 0.06-fold, p = 0.013). In T47D cells this effect was seen after 4 h of stimulation with 50 IU/ml and addition of Fas:Fc (1.6 ± 0.08-fold, p = 0.03). CONCLUSION: Membrane-bound FasL expression could be induced by IFNγ in a breast cancer cell model. More importantly, in the presence of IFNγ the Fas:Fc fusion protein was able to transmit pro-apoptotic signals to T47D and MCF7 cells, significantly inducing apoptosis. The current findings support further in vivo studies regarding FasL activation as a potential target for therapeutic intervention in breast cancer.
Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Fas Ligand Protein/metabolism , Apoptosis/drug effects , Apoptosis/physiology , Breast Neoplasms/drug therapy , Enzyme-Linked Immunosorbent Assay , Fas Ligand Protein/genetics , Female , Fluorescent Antibody Technique , Humans , Immunoglobulin Fc Fragments/genetics , Interferon-gamma/pharmacology , MCF-7 Cells , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/pharmacology , Signal Transduction/drug effectsABSTRACT
PURPOSE: A repeat Pap smear is sometimes necessary after a short time interval or even immediately, when patients seek for a second opinion or due to study participation. Only limited information is available on the possible impact of a short interval between two Pap smears. Most institutions therefore practice a minimum time span of 6-8 weeks before obtaining a second smear since a short interval is commonly believed to be associated with an increase of false negative results in the second smear. METHODS: Two consecutive Pap smears were obtained from 81 women. 41 smears were processed using the conventional technique, whereas liquid-based cytology was used in the remaining 40 women. Smears were independently evaluated by four different cytopathologists. We analyzed the effect of time interval, both processing techniques and inter-observer variance in cytological evaluation. RESULTS: While the result of the second smear shows a tendency towards a more benign outcome (odds ratio (OR) 1.436, 95% CI 0.972-2.121), this difference was not statistically significant (p = 0.07). No significant differences were observed between conservative and liquid-based cytology (OR 1.554, 95% CI 0.659-3.667, p = 0.31). There was considerable inter-observer variability, and the observer was a strong predictor of the cytological result (OR 0.632-5.083, 95% CI 0.355-8.975, p < 0.01). CONCLUSIONS: We document a tendency towards a more benign outcome without statistical significance in the second smear. Inter-observer variability of different cytopathologists is high and should be kept in mind when evaluating cytology results.
Subject(s)
Cervix Uteri/pathology , Papanicolaou Test/methods , Vaginal Smears/methods , Adult , Aged , False Negative Reactions , Female , Humans , Logistic Models , Middle Aged , Observer Variation , Odds Ratio , Prospective Studies , Sensitivity and Specificity , Time Factors , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Dysplasia/diagnosisABSTRACT
AIM: Cervical intraepithelial neoplasia (CIN) is commonly divided into three grades. Guidelines increasingly recommend surgery only in CIN 3 lesions. We investigated markers to evaluate differences in CIN 2 and 3 lesions as well as possible predictors for regression/progression in CIN 2 lesions. MATERIALS & METHODS: Biopsies (n = 128) of healthy cervical tissue and CIN 1-3 were stained for Sialyl Lewis a, Sialyl Lewis x, Lewis y, Gal-3, Gal-7, STMN1 and p16. RESULTS: We observed significant differences between CIN 2 and 3 lesions for Sialyl Lewis a, Sialyl Lewis x, Gal-3, Gal-7, STMN1 and p16. Expression of Sialyl Lewis a was significantly higher in CIN 2 patients who progressed during follow-up. CONCLUSION: Significant differences in marker expression support the differentiation of CIN 2 and 3. Lewis a may help to predict progression/regression in CIN 2 patients.
Subject(s)
Biomarkers, Tumor , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Oligosaccharides/metabolism , Stathmin/metabolism , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Dysplasia/pathology , CA-19-9 Antigen , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p16/genetics , Disease Progression , Female , Gene Expression , Humans , Immunohistochemistry , Neoplasm Grading , Sialyl Lewis X Antigen , Stathmin/genetics , Uterine Cervical Dysplasia/geneticsABSTRACT
OBJECTIVES: The incidence of cardiovascular morbidity and mortality in premenopausal women is comparatively low, but increases sharply after menopause. The principal aim of this study was to determine whether women with ascending aortic disease (AAD) have a different reproductive history from that of an age-matched control group. METHODS: In this retrospective study, women who had undergone ascending aortic aneurysm (AscAA) repair between 2000 and 2010 were asked to complete a questionnaire concerning risk factors and reproductive history. Data from 142 women with AAD were evaluated, and a subgroup (n = 64) with AscAA ≥5 cm was analyzed and compared to an age-matched random control group without known aortic diseases. RESULTS: Almost all women were menopausal at the time of the questionnaire (98.4% vs. 90.6%, AscAA ≥5 cm subcohort vs. control, p = 0.12) and all subjects presented with a comparable age of menarche (13.7 ± 2.6 years vs. 14.2 ± 1.8 years, AscAA ≥5 cm subcohort vs. control, log-rank 0.04, p = 0.84). However, mean menopausal age was significantly lower in the case subcohort than in controls (48.1 ± 4.8 years vs. 50.6 ± 5.8 years, AscAA ≥5 cm subcohort vs. control, log-rank 8.35, p = 0.004), and reproductive life span was correspondingly shorter (34.2 ± 5.2 years vs. 36.2 ± 5.7 years, p = 0.04). Furthermore, hypertension was more prevalent in women with AscAA ≥5 cm compared to controls (89.1% vs. 61.9%, AscAA ≥5 cm subcohort vs. control, p < 0.001). CONCLUSION: Women who experience menopause at an earlier age than the regional mean could profit from screening for cardiovascular disease in general and particularly for AAD. Screening would enable early aneurysm detection and could, therefore, reduce morbidity and mortality.
Subject(s)
Aortic Diseases/physiopathology , Menopause , Reproductive History , Age Factors , Aged , Case-Control Studies , Female , Germany , Humans , Menarche , Middle Aged , Retrospective Studies , Risk Factors , Surveys and QuestionnairesABSTRACT
BACKGROUND: This study aimed to identify the association of local surgery of the primary tumor in metastatic breast cancer (MBC) patients with overall survival (OS) and prognostic factors. PATIENTS AND METHODS: Patients with primary MBC (1990-2006) were included in our retrospective analysis (n = 236). 83.1% had surgery for the primary tumor. OS was evaluated using Kaplan-Meier estimates. Predictive factors for OS were determined. RESULTS: Median follow-up was 123 months for all patients still alive at the time of analysis. In univariate analysis, patients with surgery of the primary tumor had significantly prolonged OS (28.9 vs. 23.9 months). Within the surgery group, patients with MBC limited to 1 organ system had a better outcome (39.3 vs. 24.9 months), as did asymptomatic patients. Independent risk factors for shorter OS were hormone receptor negativity, symptoms, and involvement of ≥ 1 organ system. CONCLUSION: Patient selection for local therapy was confounded by a more favorable profile and a lesser tumor burden before surgery, which might implicate a bias. Nevertheless, our univariate results indicate that local surgery of the primary tumor in MBC patients could be considered as part of the therapeutic regimen in selected patients. However, larger patient numbers are needed to prove these findings in the multivariate model.