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E Kubista

Publications and source records attributed to E Kubista.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-1alpha protein secretion in breast cancer is associated with poor differentiation and estrogen receptor alpha negativity.

While interleukins (IL)-1alpha and beta are thought to play an important role in malignant disease, little is still known about their expression in breast cancer. We have used reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) to analyze the expression of IL-1alpha and beta in breast cancer tissues, and compared their expression to estrogen receptor (ER) status and grading. In breast cancer cell lines, we found an inverse correlation between IL-1alpha and beta gene expression and differentiation, and only one highly invasive tumor cell line expressed IL-1alpha protein, while IL-beta was not detectable. Breast cancer tissue expressed variable amounts of IL-1alpha and beta messenger RNA, but consistently high levels of IL-1 type I receptor. IL-1alpha protein was detectable in malignant epithelium and adjacent stroma in 88% of cases. IL-1alpha expression was correlated with poor differentiation (P= 0.002; r= 0.469) and decreasing ERalpha expression (P= 0.004; r=-0.387). Stromal IL-1alpha was confined to areas with low or absent ERalpha protein expression in adjacent tumor epithelium (P= 0.001; r=-0.457). Taken together, we have demonstrated a functional IL-1 system in breast cancer and observed an inverse correlation between IL-1alpha and sex steroid receptor expression. We suggest that the expression of IL-1alpha in poorly differentiated, ERalpha-negative tumors contributes to their malignant phenotype.

Breast Neoplasms↗
PubMed2006

Jun and Fos family protein expression in human breast cancer: correlation of protein expression and clinicopathological parameters.

OBJECTIVES: The activator protein-1 (AP-1) is a dimeric transcription factor formed by members of the Jun and Fos protein family. AP-1 plays a role in a variety of physiological functions including cell proliferation and differentiation, although both c-Jun and c-Fos have also been implicated in oncogenic transformation and tumor progression. To further elucidate the role of AP-1 in breast cancer, we have investigated the expression of the AP-1 proteins c-Jun, JunB, JunD, phosphorylated c-Jun, c-Fos, Fral, Fra2 and the tumor supressor protein p53. METHODS: Protein expression was evaluated on a breast cancer tissue microarray with 58 lymph node positive or negative breast cancer specimens, 29 corresponding lymph node metastases, and 11 tissue samples from surrounding tumor-free tissue, each cored as triplicate. Jun and Fos protein family expression was evaluated by immunohistochemistry and was correlated with clinicopathological parameters. RESULTS: High expression levels were observed for c-Jun, JunD, c-Fos and Fra2, whereas JunB and Fral exhibited lower staining. c-Jun protein expression was correlated to Fral staining (p = 0.007, Kendall's Tau) and Fral was further associated with c-Fos (p < 0.001), JunD (p = 0.001) and Fra2 (p = 0.011) expression. JunD expression correlated with c-Fos (p < 0.001), JunB (p = 0.035) and c-Jun (p = 0.05). Activated c-Jun correlated with c-Fos expression (p = 0.041). JunB was negatively correlated to tumor stage, (p = 0.093, corr coeff. = -0.293, Spearman's correlation) but was significantly increased in nodal negative tumors (p = 0.004, Mann Whitney test). In addition, increased Fral expression showed a trend towards an increased overall survival (p = 0.077, RR = 0.534, Cox regression). CONCLUSION: Our results suggest an important role for JunB and Fral in the biological behavior of malignant breast tumors.

Biomarkers, Tumor↗
PubMed2005

Interleukin 1alpha and tissue-lytic matrix metalloproteinase-1 are elevated in ectopic endometrium of patients with endometriosis.

BACKGROUND: Matrix metalloproteinases (MMP) play an essential role in tissue remodelling and menstruation and appear to be regulated by cytokines such as interleukin-1alpha (IL-1alpha). In order to investigate their role in the pathogenesis of endometriosis, the aim of the present study was to compare the protein localization of matrix metalloproteinase-1 (MMP-1) and of its main stimulatory cytokine IL-1alpha in eutopic and dystopic endometrium of patients with endometriosis. METHODS: MMP-1 and IL-1alpha protein localization was analysed retrospectively in paired paraffin-embedded tissue biopsies obtained simultaneously from the endometrial cavity and from endometrial lesions of 37 patients with peritoneal or ovarian endometriosis and in cycling endometria from 37 women without endometriosis. Protein localization was demonstrated by immunohistochemistry; antibody specificity was confirmed by western blot analysis. RESULTS: MMP-1 and IL-1alpha protein staining in women suffering from endometriosis was significantly more pronounced in endometriotic lesions than in eutopic endometrium. This held true for both epithelial MMP-1 and IL-1alpha staining (P < 0.006 and P < 0.001), and for stromal MMP-1 and IL-1alpha staining (P < 0.001 and P < 0.001). Furthermore, stromal MMP-1 and IL-1alpha were significantly co-expressed in dystopic endometriotic tissue (P = 0.045). Endometrial MMP-1 and IL-1alpha protein expression pattern in eutopic endometrium from women suffering from endometriosis, however, did not differ significantly from the pattern seen in healthy women. CONCLUSIONS: The increased expression of both matrix-degrading MMP-1 and its major stimulatory cytokine IL-1alpha in endometriotic lesions and the selective co-expression in the stroma of endometriotic foci clearly suggests their involvement in the pathogenic mechanisms leading to local invasion and tissue destruction.

Adult↗
PubMed2005

The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer. DESIGN: Double-blind, randomised, placebo-controlled, multicentre pilot study. SETTING: Hospital outpatient clinic. SAMPLE: Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer. METHODS: Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months. MAIN OUTCOME MEASURES: Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins. RESULTS: Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23% vs 1.4%) and HDL (-12% vs 19%) was seen with tibolone compared with placebo after 12 months. CONCLUSIONS: Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted.

Administration, Oral↗
PubMed2004

Physical state and expression of HPV DNA in benign and dysplastic cervical tissue: different levels of viral integration are correlated with lesion grade.

OBJECTIVE: Human papillomavirus (HPV) infection is the most important event in the malignant transformation of human cervical epithelium. Several high-risk (HR-)HPV subtypes have been identified, which lead to CIN and subsequently to invasive carcinoma. The reason for this phenomenon is still unknown, but it seems to be related to the physical state of HPV DNA. METHODS: Digene HC II test was used to identify HR- and/or low-risk (LR-)HPV infections in cervical swabs of 275 women attending our clinic for routine cytological screening and/or colposcopy because of an abnormal Pap smear comprising low-grade squamous intraepithelial lesions (LGSIL) and high-grade SIL (HGSIL). Specific HR (16, 18, 31, 33, 52b, 58) and LR (6, 11) subtypes were characterized in cervical biopsies of 10 women with benign cellular changes and of 68 women with CIN I-III by the PCR-restriction enzyme method. The physical state of HPV DNA (episomal, mixed and integrated form) was analyzed by bi-dimensional (2D)-gel electrophoresis. In addition, mRNA expression of E6/E7 genes was analyzed by RT-PCR. Furthermore, the relative virus load was determined in nine selected cases. The physical state and transcriptional activity of HPV DNA were then correlated to histopathological results. RESULTS: LR-HPV infection [27 cases (9.8%)] and HR-HPV infection [121 cases (44%)] of cervical swabs were clearly correlated to the degree of SIL. Further HPV typing in cervical biopsies of 78 women showed that HPV6 and 11 were restricted to benign cellular changes, CIN I and II, whereas HPV16 and 18 were observed predominantly in CIN III/CIS (P=0.01). No clear distribution pattern was observed for HPV31, 33, 52b and 58. Expression of HPV E6 and E7 transcripts was uniformly correlated with the different physical state of HPV DNA. Analyzing the physical state of these HPV subtypes, HPV6 and 11 could only be detected as an episomal form, independent of SIL grade. In normal epithelium and in CIN I and II, HPV16 and 18 were exclusively found in the episomal form. In CIN III/CIS, 15 of 30 cases of HPV16 (50%) and 16 of 17 cases of HPV18 (94%) were exclusively integrated into the host genome. Like HPV16/18, HPV31, 33, 52b and 58 were also present in the episomal form in normal epithelium and in CIN I and II, but were integrated in 80% of the CIN III/CIS (4/5) cases. CONCLUSION: Absent integration of HPV16 DNA in some CIN III/CIS suggests that integration is not always required for progression early dysplastic lesions. In contrast, integration of HPV type 18 and others appears to be of major importance for the transforming efficacy of cervical dysplasia. The applied method represents a sensitive instrument to assess the physical state of HPV and is useful to predict the progression of disease.

Adult↗
PubMed2004

Breast cancer size in postmenopausal women is correlated with body mass index and androgen serum levels.

Our objective was to investigate the effects of age, weight, body mass index (BMI), sex steroid receptor status and serum parameters such as estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and leptin on the size of a malignant breast tumor. A total of 62 premenopausal (median age 44.0 years) and 151 postmenopausal (median age 59.1 years) Caucasian women undergoing lumpectomy or mastectomy for invasive breast cancer were examined. Patient parameters (age, body weight, BMI), tumor parameters (tumor size, estrogen and progesterone receptor status) and serum parameters (estradiol, testosterone, androstenedione, DHEAS and leptin) were measured. An increase of BMI and DHEAS levels was associated with larger tumors by partial correlation (rp) analysis (rp = 0.418, p = 0.008; and rp = 0.329, p = 0.041, respectively), whereas higher androstenedione levels corresponded with smaller tumors. Furthermore, BMI, androstenedione and DHEAS levels were correlated: an increase in DHEAS was associated with higher androstenedione serum concentrations (rp = 0.603, p < 0.001), but was also associated with a lower BMI (rp = -0.378, p < 0.001). BMI and androstenedione serum concentrations were also associated (rp = 0.242, p = 0.009), thus closing a circle of mutual interactions. We conclude that, although breast cancer progression is characterized by autonomous growth that has become independent of growth regulatory mechanisms, tumor size at the time of detection is influenced by a complex system of counter-regulatory feedback mechanisms that might represent the body's physiological attempt to control the size of a malignant tumor.

Adult↗
PubMed2004

Presence of nanobacteria in psammoma bodies of ovarian cancer: evidence for pathogenetic role in intratumoral biomineralization.

AIMS: The presence of laminated, calcified extracellular debris known as psammoma bodies is a well-known histomorphological feature of ovarian adenocarcinomas and other human malignancies. Biomineralization has recently been found to be associated with a group of extremely small Gram-negative bacteria capable of precipitating calcium salts. The aim of the present study was to evaluate a possible pathogenic link between the development of psammoma bodies and nanobacteria infection. MATERIAL AND RESULTS: Immunohistochemical staining and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to analyse nanobacterial protein and gene expression in eight psammona body-containing adenocarcinomas and in 10 malignant ovarian tumours without signs of biomineralization. Nanobacterial proteins were detected in eight out of eight (100%) psammoma-positive tumour samples. Conversely, none of the 10 psammoma-negative tissues (0%) was positive for nanobacterial antigens. Furthermore, nanobacterial mRNA was detectable in all of the four tissues (100%) that contained psammoma bodies, but was absent in all 10 ovarian cystadenocarcinomas (0%) that were psammoma negative. CONCLUSIONS: We found a 100% concordance between the expression of nanobacteria and the presence of psammoma bodies in malignant ovarian tumours. Several lines of evidence suggest the involvement of these organisms in the process of biomineralization. We therefore conclude that nanobacterial infection of malignant ovarian tissue contributes to mechanisms leading to the formation of calcified deposits known as psammoma bodies.

Adenocarcinoma↗
PubMed2004

Predicting the clinical course of breast cancer patients undergoing trastuzumab-based therapy: an outlook.

Her-2/neu overexpressing breast cancer is associated with reduced overall survival, sex steroid receptor negativity and increased resistance to antihormonal therapy, and thus represents a subgroup with poor prognosis. The anti Her-2/neu receptor antibody trastuzumab (Herceptin), however, specifically targets this protein and provides a valuable addition to classical systemic therapies. Unfortunately, not all tumors that express Her-2/neu protein are also adequate candidates for trastuzumab therapy. Therefore, most clinicians now consider Her-2/neu oncoprotein overexpression and/or her-2/neu gene amplification a prerequisite for trastuzumab-based antineoplastic therapy. Nevertheless, due to the relatively low response rates that are observed even in this preselected patient cohort, better response predictors are clearly needed. Here, we review established parameters such as Her-2/neu immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and their ability to predict the clinical course of trastuzumab-treated breast cancer. We also evaluate promising parameters such as serum levels of the Her-2/neu extracellular domain (ECD) and the activation status of Her-2/neu oncoprotein (pHer-2/neu), and their use in the clinical setting. Finally, novel tumor-specific such as tumor M2-PK, IGF-IR and p53 are discussed and their potential to predict the efficacy of trastuzumab is assessed.

Animals↗
PubMed2003

Her-2/neu-triggered intracellular tyrosine kinase activation: in vivo relevance of ligand-independent activation mechanisms and impact upon the efficacy of trastuzumab-based treatment.

Proteolytic cleavage of the Her-2/neu extracellular domain (ECD) has been shown to initiate receptor phosphorylation representing Her-2/neu activation in vitro. The present investigation was performed to evaluate the clinical relevance of ECD cleavage for Her-2/neu activation and the consequences of active intracellular Her-2/neu signalling reflected by tyrosine kinase phosphorylation in patients treated with the anti-Her-2/neu antibody trastuzumab. Sera from 62 patients receiving trastuzumab-based treatment for Her-2/neu overexpressing metastatic breast cancer were assessed for pretreatment ECD levels using an enzyme-linked immunosorbent assay. In parallel, Her-2/neu activation status of tumour specimens was assessed by immunohistochemistry using a Her-2/neu phosphorylation state specific antibody (PN2A) and correlated with the patients' ECD levels and clinical course of disease. Serum ECD levels were significantly higher in 15 (24%) patients with tumours exhibiting activated Her-2/neu as compared to those without detectable Her-2/neu phosphorylation (median 148.2 vs 28.5 ng ml(-1), P=0.010). Whereas response rate only showed a trend to be higher in patients with Her-2/neu-phosphorylated breast cancer (47 vs 34%, P=0.197), both uni- and multivariate analyses revealed that the median progression-free survival under trastuzumab-based treatment was significantly longer in patients with Her-2/neu-phosphorylated breast cancer-11.7 (95% CI 5.2-18.3) months-when compared to the progression-free survival of 4.5 (95% CI 3.4-5.6) months observed in patients with tumours lacking phosphorylated Her-2/neu (P=0.001). Proteolytic cleavage of the ECD represents a biologically relevant ligand-independent mechanism of Her-2/neu activation in vivo. The influence of Her-2/neu activation status upon the outcome of trastuzumab-based therapies merits further investigation in larger prospective trials.

Adult↗
PubMed2003

Co-expression of ErbB-family members in human breast cancer: Her-2/neu is the preferred dimerization candidate in nodal-positive tumors.

Over-expression of members of the ErbB-receptor family has been associated with malignant transformation. The amplification of Her-2/neu in tumor tissue is now an established prognostic factor in breast cancer. In order to initiate signal transduction, ErbB-receptor monomers need to form homo- or heterodimers. The composition of these dimers is thought to influence both quality and quantity of downstream signaling pathways, and to determine the biological response. We have investigated the protein expression pattern of the four ErbB-receptors EGFR, Her-2/neu, Her-3 and Her-4, and correlated it with their putative ligands EGF, TGF-alpha and HRG in 74 women with invasive breast cancer. Using western blot-analysis on cell membrane isolates, we detected the co-expression of all four ErbB-family members in 79.7% of cases, and of all of the three investigated ligands in 82.4%. We did not observe a correlation between EGFR and Her-2/neu or Her-4 protein expression, EGFR and Her-3 (p = 0.005), and Her-3 and Her-4 (p = 0.05) were clearly co-expressed. The strongest overall correlation, was found between Her-2/neu and Her-3 (p < 0.001) and between Her-2/neu and Her-4 (p = 0.001). This was particularly true in nodal-positive tumors (p < 0.001 and p = 0.002) whereas in nodal-negative tumors the co-expression was either less significant (Her-2/neu and Her-3; p = 0.01) or not significant (Her-2/neu and Her-4). The co-expression of EGFR/Her-3 was associated with the expression of all ligands, whereas the Her-2/neu/Her-3 was correlated with HRG (p = 0.002), thereby indicating a functional relation between specific receptor-dimer combinations and putative ligands. Taken together, we have performed the first comprehensive survey of ErbB-system expression in breast cancer, and have demonstrated the presence of a co-regulated receptor/ligand system in vivo. We have further shown that Her-2/neu is the preferred co-expression partner in nodal-positive tumors and thus the most likely dimerization candidate in malignant breast tumors.

Adult↗
PubMed2003

Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients.

AIM: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. PATIENTS AND METHODS: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. RESULTS: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. CONCLUSIONS: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Interleukin-1 system and sex steroid receptor gene expression in human endometrial cancer.

OBJECTIVES: The interleukin-1 system is known to play a pivotal role in human physiology and reproduction. In the cycling endometrium, interleukin-1alpha activity is controlled by sex steroids and is confined to the perimenstrual phase, where it is involved in the events leading to tissue lysis and menstruation. Since local tissue degradation is also a feature of malignant tumors, our goal was to analyze the gene expression of interleukin-1alpha and other interleukin-1 family members and compare it with estrogen receptor alpha, estrogen receptor beta, and progesterone receptor mRNA expression in 27 endometrial carcinomas and 13 normal endometria. METHODS: Endometrial tumor tissues were obtained during hysterectomy for endometrial cancer, and normal endometrium was sampled in women undergoing surgical procedures for nonendometrial pathologies. Gene expression was analyzed by reverse transcription polymerase chain reaction. Protein expression was detected and localized by immunohistochemical staining. RESULTS: A strong gene expression of interleukin-1 type I receptor, estrogen recptor alpha, and progesterone receptor was detected in all tumor tissues and in the majority of benign endometrial tissues. However, in contrast to nonmalignant endometria, variable amounts of interleukin-1beta and interleukin-1 receptor antagonist mRNA were also detected in most of the tumor samples. Gene expression of interleukin-1alpha and estrogen receptor beta was considerably less frequent, with interleukin-1alpha being absent in all peri- and postmenopausal endometria and in all but one of the well-differentiated tumors. With decreasing differentiation interleukin-1alpha gene expression became more frequent. In these cases, interleukin-1alpha protein was detected predominantly in epithelial tumor cells of lower-grade tumors. CONCLUSION: We have demonstrated the presence of the interleukin-1 system in endometrial malignancies, and found a negative correlation between interleukin-1alpha and tumor differentiation. We hypothesize that the nonphysiological expression of interleukin-1alpha in less differentiated tumors might contribute to their invasiveness and malignant behavior.

Carcinoma, Endometrioid↗
PubMed2002

Influences of stroma-derived growth factors on the cytokine expression pattern of human breast cancer cell lines.

Tumor growth and local invasion are greatly dependent on the malignant potential of a tumor cell, but are also significantly modulated by a variety of local factors. These factors comprise cytokines, growth factors and extracellular matrix proteins (ECM), which act through a complex system of auto-, para- and juxtacrine interactions. Some factors are produced by the malignant cell itself, others are expressed by adjacent tumor stroma, migrated inflammatory cells, or resident macrophages. We have investigated the influences of cytokines and growth factors known to be expressed by tumor stroma on the cytokine expression pattern of three human breast cancer cell lines of different malignant potential. MCF-7, T47D and MDA-MB-231 were incubated with human recombinant TNF-alpha, IGF-I, IGF-II, bFGF, HGF or G-CSF and the pattern of tumor-cell-derived TGF-beta1, bFGF, IL-1alpha and VEGF was analyzed. Among the three cell lines used we observed a heterogenous response to stromal cytokines by measuring above mentioned factors in the cell culture's supernatants, but no clear correlation between malignant potential and cytokine expression pattern seemed obvious. We hypothesize that local growth factors may have a significant modulatory effect on malignant behavior in vivo. We conclude that this effect might depend on individual responses and on the differentiation state of tumor cells.

Breast Neoplasms↗
PubMed2001

Docetaxel monotherapy in heavily pretreated metastatic breast cancer: a multicenter, community-based feasibility trial.

PURPOSE: To evaluate the efficacy and safety of docetaxel in heavily pretreated and anthracycline-resistant patients with metastatic breast cancer in an outpatient setting. PATIENTS AND METHODS: Between February 1996 and June 1998, 98 consecutive patients who had progressed during or relapsed following prior anthracycline-containing chemotherapy were enrolled into the trial. Docetaxel was administered at a dose of 100 mg/m2 by intravenous infusion every 3 weeks. The administration of colony-stimulating factors was at the discretion of the attending physician. Premedication with dexamethasone was mandatory for all patients. RESULTS: Of the 98 patients, 93 were evaluable for toxicity and response. Patients had received two palliative regimens (median, range 1-5) prior to docetaxel treatment. The most frequent toxicity observed was leukopenia grade III and IV (WHO grading system) which occurred in 47% of patients (grade IV only in 14%). Except for alopecia grade III (64% of patients), nonhematologic side effects grade III-IV were rare (1-7% of patients) and included nausea, stomatitis, diarrhea, peripheral neuropathy, fluid retention and pulmonary toxicities. There were no treatment-related deaths. Objective responses occurred in 40% of patients (CR 6%, PR 34%), and stable disease in 38% of patients. The median duration of response was 5.3 months (range 0.7-18.1 months) while the median survival was 15 months (range 2 36 months). CONCLUSION: Docetaxel is a highly active agent in patients with anthracycline-resistant metastatic breast cancer, even in heavily pretreated patients, with moderate toxicity.

Adolescent↗
PubMed2001

Circulating breast cancer cells are frequently apoptotic.

Automatic search for cytokeratin/mucin-1 double immunofluorescence was performed to detect and characterize circulating epithelial tumor cells in patients with advanced breast cancer. The peripheral blood samples in 8 of 19 patients (42.1%) presented with cytokeratin-positive and epithelial-type mucin-positive (CK(+)/MUC1(+)) tumor cells. Detailed microscopic analysis, however, suggested that the majority of the double immunopositive cells was apoptotic according to an "inclusion type" cytokeratin staining pattern and nuclear condensation. Furthermore, apoptosis-related DNA strand breaks could be demonstrated by applying the TdT-uridine nick end labeling assay in these cells. In 3 of 8 positive samples all of the CK(+)/MUC1(+) cells displayed apoptotic features. We conclude that apoptotic cells significantly contribute to the circulating tumor cell fraction in breast cancer patients. As the predictive value of such cells for the outcome of the disease is unclear, they should be considered separately when analyzing tumor cell dissemination.

Apoptosis↗
PubMed2001

Sealing of postoperative axillary leakage after axillary lymphadenectomy using a fibrin glue coated collagen patch: a prospective randomised study.

Seroma formation after axillary lymphadenectomy in women with breast cancer remains a problem despite many efforts to reduce surgery-related morbidity. In a prospective, randomised, open, parallel-group, controlled clinical trial we evaluated the effect of a fibrin-glue coated collagen patch (TachoComb H, Nycomed Pharma AS, Denmark) on volume and duration of postoperative axillary drainage, duration of hospital stay, and procedural safety. Sixty patients were included in the study. Patients did not differ with respect to general characteristics, such as age, body mass index, treatment modality, and tumor stage distribution. In 29 patients, a fibrin-glue coated collagen patch was applied from the apex axillae to the thoracic longus nerve and half a patch was applied to the lateral border of the axillary nerve-vessel bundle. Thirty-one patients were randomised to standard closure of the axillary lymphadenectomy area. The mean duration of axillary drainage was 3.8 +/- 1.9 days in the fibrin-glue treatment group and 3.9 +/- 1.8 days in the control group (p = NS). The mean total drainage volume was 338.5 +/- 251.8 ml in the fibrin-glue treatment group and 370.8 +/- 314.6 ml in the standard closure group (p = NS). The mean length of post-operative hospital stay was 9.1 +/- 2.7 days in the fibrin-glue treatment group and 9.3 +/- 3.6 days in the standard closure group (p = NS). Seven patients (25%) and eight patients (25%) were diagnosed with local inflammation in the fibrin-glue treatment group and the standard closure group, respectively (p = NS). Seroma formation after drain removal was found in 11 patients (39%) in the fibrin-glue treatment group and in 13 patients (42%) in the standard closure group (p = NS). In summary, we observed no statistically significant differences with respect to axillary drainage time, drainage volume, length of hospital stay, local inflammation, and seroma formation after drainage removal.

Axilla↗