Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach

Noninvasive biomarkers are urgently needed for early detection of breast cancer since the risk of recurrence, morbidity and mortality are closely related to disease stage at the time of primary surgery. In the past decade, many proteomics-based approaches were developed that utilize the protein profiling of human body fluids or identification of putative biomarkers to obtain more knowledge on the effects of cancer emergence and progression. Herein, we report on an analysis of proteins in the tear fluid from breast carcinoma patients and healthy women using a de novo proteomic approach and 25 mixed samples from each group. This study included 25 patients with primary invasive breast carcinom…

Skin-reducing Mastectomy with Primary Implant Reconstruction

Background: We present a series of skin-sparing mastectomies (SSMs) with skin reduction and immediate breast reconstruction to treat large and ptotic breasts. The technique combines oncological mastectomy with immediate subpectoral implant placement as a single-step procedure. Methods: Data was collected from a prospective database from February 2009 to April 2011. A total of 24 patients with macromastia or pronounced ptosis fulfilled the criteria for skin-saving mastectomy. All operations were carried out as a single-step procedure with adaptation of the contralateral breast by reduction mastopexy. Results: A total of 27 SSMs were performed in 24 patients. The mean implant volume was 265 c…

The prognostic value of four interleukin-1 gene polymorphisms in caucasian women with breast cancer – a multicenter study

Abstract Background The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown. Methods We studied the influence of four common gene polymorphisms (IL1A -889C/T, IL1B -511C/T, IL1B +3953E1/E2, and IL1RN long/2) of the IL-1 family on survival in 262 Caucasian patients with breast cancer by univariate and multivariate survival analysis. The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis. Resu…

Serum proteome profiling of primary breast cancer indicates a specific biomarker profile.

Non-invasive biomarkers for early breast cancer detection are urgently needed, as the risk of recurrent morbidity and mortality is closely related to the stage of the disease at the time of primary surgery. Currently, there are no established clinical biomarkers for breast cancer. Evaluation of protein expression patterns in body fluids using proteomic technologies can be used to discover new biomarkers for the detection of breast cancer. The aim of this study was to identify a biomarker signature identifying primary non-metastatic breast cancer and healthy controls. We screened 91 serum samples including 45 breast cancer patients and 46 healthy women using a proteomic approach. We found 14…

Comparison of Prognostic Signatures in Node-Negative Tamoxifen-Treated Breast Cancer Patients.

Abstract Background: A number of molecular signatures have been published to aid breast cancer prognosis and therapy response prediction. A 76-gene signature has been developed in a node-negative patient cohort that did not receive systemic therapy.1 Another prognostic 97-gene signature measures predominantly proliferation-associated genes.2 Finally, a 21-gene signature has been developed for node-negative and estrogen receptor–positive breast cancer patients treated with tamoxifen in the adjuvant setting.3 Here we compare the prognostic performance of all three published algorithms in a cohort of 189 node-negative breast cancer patients treated with tamoxifen.Materials and Methods: Fresh-f…

[Current developments and perspectives on the diagnosis and treatment of urinary incontinence and genital prolapse in women].

As a key area of gynaecology, urogynaecology has undergone impressive changes in the past few years. Together with the high prevalence of functional pelvic floor disorders, modern anaesthesia procedures and the introduction of new, innovative minimally invasive operation techniques have led to a dramatic increase in the number of operations for incontinence and prolapses. The increasingly subtle diagnostic options, such as, e. g., 2D and 3D sonography of the pelvic floor provide unambiguous findings and facilitate decision making. Tension-free vaginal slings in retro-pubic, trans-obturator or single-incision techniques show a high success rate with few complications and have almost complete…

p53 is correlated with low BMI negative progesterone receptor status and recurring disease in patients with endometrial cancer

Abstract Objective P53 tumor suppressor gene plays a role in endometrial carcinogenesis. Former studies described correlations between p53 protein overexpression in endometrial cancer and prognostic factors, measured by immunohistochemistry. But data is still controversial. The aim of this study was to measure p53 and phospho-p53 overexpression by Western blot and evaluate correlations between overexpression and prognostic and clinical factors. Phospho-p53 seems to be the functional p53 protein and was examined for the first time in endometrial cancer. Methods 40 patients with endometrial cancer were included in the study. A control group of 20 patients with normal endometrial tissue sample…

Prospective randomized comparison of conventional instruments and the Harmonic Focus(®) device in breast-conserving therapy for primary breast cancer.

Abstract Background In recent years, surgeons have utilized Harmonic instruments to perform breast cancer resection. Retrospective and prospective studies have demonstrated that the use of this surgical device for mastectomy and axillary dissection can reduce perioperative blood loss, seroma formation, and duration and total amount of drainage. No study has analyzed the feasibility of Harmonic instruments in breast-conserving surgery. We conducted a prospective, randomized clinical trial comparing Harmonic instrument and conventional surgery in the performance of breast-conserving surgery and axillary procedures to determine differences in surgical procedures, postoperative outcome, and com…

Nuclear expression of apurinic/apyrimidinic endonuclease increases with progression of ovarian carcinomas.

Apurinic/apyrimidinic endonuclease (APE alias Ref-1) is a key enzyme in the base excision repair pathway. Besides its function in DNA repair, APE serves to maintain several transcription factors in an active reduced state such as c-Fos, c-Jun, NF-kappaB, p53 and HIF-1alpha, all of which have been shown to play a role in tumorigenesis. Because of the importance of APE in maintaining genomic stability and gene regulation, we examined whether APE expression is associated with survival and histopathological parameters of patients with ovarian cancer.Tissue sections of primary epithelial ovarian carcinomas from 141 patients were immunostained using a monoclonal antibody directed against APE.Nucl…

Phase II study of fulvestrant 250mg/month in patients with recurrent or metastatic endometrial cancer: A study of the Arbeitsgemeinschaft Gynäkologische Onkologie

Abstract Objectives The aim of this study is to evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). Methods Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250mg by IM injection every 4weeks for at least 12weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. Results Thirty-five patients w…

Operative Therapie bei Genitaldeszensus der Frau: Pro und Kontra der Verwendung von Mesh-Materialien

Die gegenwärtige Entwicklung unterschiedlicher Mesh-Materialien hat zu einer Verbesserung der individuellen operativen Sanierung des Genitalprolapses geführt. Makroporöse monofilamentäre synthetische Netze scheinen geeignet zur Verwendung beim Rezidivprolaps oder bei ausgeprägten Beckenbodeninsuffizienzen zu sein. Die Verwendung von biologischen Netzen zeigt eine deutlich bessere Verträglichkeit mit weniger Infektionen oder Erosionen, bislang ist jedoch nicht das Problem der langfristigen Haltbarkeit geklärt. Die operative Korrektur des Genitalprolapses muss alle Risiken und Nutzen zur Verbesserung der Lebensqualität abwägen, hier können Mesh- Materialien deutliche Vorteile gerade in der Re…

Combination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: A prospective phase II study of the Arbeitsgemeinschaft Gynäekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and Kommission Uterus (AGO-K-Ut)

Abstract Objective. A multicenter non-randomized phase II study was initiated to evaluate tolerability and efficacy of pegylated liposomal doxorubicin (PLD) in combination with carboplatin in gynecologic malignancies. Methods. One hundred forty women with recurrent or advanced endometrial ( n =31), cervical or vaginal cancer ( n =31), uterine sarcomas ( n =11), or recurrent platinum-sensitive ovarian cancer ( n =67) received six courses of PLD 40 mg/m 2 and carboplatin (AUC 6) every 28 days. Results. Hematological toxicities with NCI-CTC grade 3/4 were anemia in 8%, thrombocytopenia in 14%, neutropenia in 24%, and febrile neutropenia in 2% of 652 cycles. Grade 3/4 non-hematological toxiciti…

ERBB2 Induces an Antiapoptotic Expression Pattern of Bcl-2 Family Members in Node-Negative Breast Cancer

AbstractPurpose: Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.Experimental Design: ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis…

Cervical Cancer Screening: Comparison of Conventional Pap Smear Test, Liquid-Based Cytology, and Human Papillomavirus Testing as Stand-alone or Cotesting Strategies

Abstract Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study. Methods: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blottin…

4-Epidoxycycline: an alternative to doxycycline to control gene expression in conditional mouse models

Since the pioneering work by Gossen and Bujard in 1992 demonstrating the usefulness of the Escherichia coli derived tet resistance operon for regulating gene expression a large collection of doxycycline-controlled transgenic mice has been established. Gene switching in eukaryotic tissue culture cells or mice requires administration of tetracycline, anhydrotetracycline or doxycycline to efficiently inactivate the transactivator protein tTA (TET-OFF system) or alternatively to activate the reverse transactivator protein rtTA (TET-ON system). However, the antibiotic activity of doxycycline can create an imbalance of the intestinal flora, resulting in diarrhoea and in a smaller number of animal…

Antibody microarray analysis of the serum proteome in primary breast cancer patients

Noninvasive biomarkers are urgently needed for detecting breast cancer as early as possible since the risk of recurrence, morbidity, and mortality is closely related to disease stage at the time of primary surgery. There are currently no such biomarkers in clinical use as a diagnostic tool. Proteomic analysis of protein expression patterns in body fluids has potential for use in identifying biomarkers of breast cancer. The aim of this study was to compare protein expression levels in the sera of primary breast cancer patients and healthy controls. An antibody microarray tool with 23 antibodies immobilized on nitrocellulose slides was used to determine the levels of acute phase proteins, int…

The humoral immune system has a key prognostic impact in node-negative breast cancer.

Abstract Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with…

Enzyme replacement therapy with agalsidase alfa in pregnant women with Fabry disease

Eminence, or rather eloquence, or rather economy-based medicine?

Dephosphorylation of p-ERK1/2 in relation to tumor remission after HER-2 and Raf1 blocking therapy in a conditional mouse tumor model

Several studies have shown that HER-2/neu (erbB-2) blocking therapy strategies can cause tumor remission. However, the responsible molecular mechanisms are not yet known. Both ERK1/2 and Akt/PKB are critical for HER-2-mediated signal transduction. Therefore, we used a mouse tumor model that allows downregulation of HER-2 in tumor tissue by administration of anhydrotetracycline (ATc). Switching-off HER-2 caused a rapid tumor remission by more than 95% within 7 d of ATc administration compared to the volume before switching-off HER-2. Interestingly, HER-2 downregulation caused a dephosphorylation of p-ERK1/2 by more than 80% already before tumor remission occurred. Levels of total ERK protein…

Lymph node ratio in inguinal lymphadenectomy for squamous cell vulvar cancer: Results from the AGO-CaRE-1 study.

Lymph node ratio (LNR) can predict treatment outcome and prognosis in patients with solid tumors. Aim of the present analysis was to confirm the concept of using LNR for assessing outcome in patients with vulvar cancer after surgery with inguinal lymphadenectomy in a large multicenter project.The AGO-CaRE-1 study multicenter database was used for analysis. LNR was defined as ratio of number of positive lymph nodes (LN) to the number of resected. Previously established LNR risk groups were used to stratify patients. LNR was investigated with respect to clinical parameters. Univariate and multivariable survival analyses were performed to assess the value of LNR in order to predict overall (OS…