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A Rody

Publications and source records attributed to A Rody.

At least 19 recordsLinked to original sources
PubMed2006

Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response.

Gene expression analysis in breast cancer patients undergoing neoadjuvant chemotherapy is an interesting tool for identification of gene signatures and new markers to predict tumor response. However, the detection of predictive markers strongly depends on the drugs used in the specific therapeutic setting. There is growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for anthracycline-, and microtubule-associated protein tau (MAPT) for taxane sensitivity. HER-2 has been described as a marker of both anthracycline and taxane sensitivity. We performed gene expression profiling of 50 patients within the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial. Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA expression for pathological complete response (pCR) in this setting. Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as well as overall response (P=0.037) and clinical complete response (cCR, P=0.050). In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed in our sample group.

Adult↗
PubMed2006

Uterotubal transport disorder in adenomyosis and endometriosis--a cause for infertility.

OBJECTIVE: Uterine hyperperistalsis and dysperistalsis are common phenomena in endometriosis and may be responsible for reduced fertility in cases of minimal or mild extent of disease. Since a high prevalence of adenomyosis uteri has been well documented in association with endometriosis, we designed a study to examine whether hyperperistalsis and dysperistalsis are caused by the endometriosis itself or by the adenomyotic component of the disease. DESIGN: A prospective observational study. SETTING: University hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 300 in vitro fertilisation/intracytoplasmatic sperm injection cycles and 350 intrauterine insemination cycles/year. POPULATION: Forty-one subjects with infertility and with laparoscopically proven endometriosis and patent fallopian tubes. Thirty-five subjects (85%) additionally showed signs of adenomyosis. METHODS: All subjects underwent T2-weighed magnetic resonance imaging (MRI) and hysterosalpingoscintigraphy (HSSG) during the subsequent menstrual cycle. MRI revealed the extent of the adenomyotic component of the disease and the integrity of uterotubal transport capacity was evaluated by HSSG. MAIN OUTCOME MEASURES: Influence of adenomyosis on uterotubal transport capacity in endometriosis. RESULTS: In 35 of the 41 subjects (85%) with endometriosis, signs of adenomyosis were detected using T2-weighed MRI. Two of six (33%) subjects with no adenomyosis (group I) showed dysperistalsis and hyperperistalsis, compared with 14 of 24 (58%) women with focal adenomyosis (group II) and 10 of 11 (91%) women with diffuse adenomyosis (seven showed a failure in transport capacity and two contralateral transport). CONCLUSIONS: Our data suggest that endometriosis is associated with impeded hyperperistaltic and dysperistaltic uterotubal transport capacity. However, adenomyosis is of even more importance, especially when diffuse adenomyosis is detected. Both forms of adenomyosis are commonly found in subjects with mild to moderate endometriosis. We suggest that the extent of the adenomyotic component in subjects with endometriosis explains much of the reduced fertility in subjects with intact tubo-ovarian anatomy.

Adenomyoma↗
PubMed2006

Gene expression profiles of breast cancer obtained from core cut biopsies before neoadjuvant docetaxel, adriamycin, and cyclophoshamide chemotherapy correlate with routine prognostic markers and could be used to identify predictive signatures.

BACKGROUND: Neoadjuvant administration of chemotherapy provides a unique opportunity to monitor response to treatment in breast cancer and assesses response exactly. Global gene expression profiling by microarrays has been used as a valuable tool for the identification of prognostic and predictive marker genes. Even though this technology is now wide spread and relatively standardized, there are only few data available which compare established parameters with expression values to determine reliability of this method. Therefore we analyzed gene expression data of pretreatment biopsies of breast cancer patients and compared them with the results of the immunohistochemical receptor expression for ER/ PR and Her-2, as well as FISH testing for HER-2 amplification. We analyzed the change of expression of these markers before and after neoadjuvant chemotherapy. Furthermore we evaluated the predictive significance of prognostic gene signatures as described by Sorlie, van't Veer and Ahr for response to neoadjuvant chemotherapy. METHODS: Pretherapeutic core biopsies were obtained from 70 patients undergoing neoadjuvant TAC chemotherapy within the GEPARTRIO-trial. Samples were characterized according to standard pathology including ER, PR and HER2 IHC and amount of cancer cells. Only biopsies with more than 80 % tumor cells were considered for further examination. RNA was isolated and expression profiling performed using Affymetrix Hg U133 Arrays (22 500 genes). GeneData's Expressionist software was used for bioinformatic analyses. RESULTS: More than two thirds of the biopsies yielded sufficient amounts (> 5 microg) of RNA for expression profiling and high quality data were obtained for 50 samples. Unsupervised clustering broadly revealed a correlation with hormone receptor status. When ER-alpha, PR and HER2 as analyzed by immunohistochemistry were compared to the corresponding mRNA data from gene chips more than 90 % concordance was observed. We could observe a switch of receptor expression for ER, PR or HER-2 from positive to negative and vice versa in 16/35 cases (45.7 %) and 5/22 cases (22.7 %) respectively. The prognostic marker sets of Sorlie, van't Veer and Ahr could not discriminate responders from non-responders in our patient group. CONCLUSIONS: Our results demonstrate that reliable expression profiles can be achieved by using limited amounts of tissue obtained during neoadjuvant chemotherapy. Microarray data capture conventional prognostic markers but might contain additional informative gene sets correlated with treatment outcome. Prognostic marker sets are not suitable to predict tumor response in the neoadjuvant setting, suggesting the necessity of class prediction methods to identify marker sets predictive for the type of therapy used.

Adult↗
PubMed2006

[Integrin expression in eutopic and ectopic endometrium].

The significance of retrograde menstruation as a risk factor for endometriosis has been confirmed by numerous clinical observations. Integrins mediate both cell-cell and cell-matrix adhesion, and it is therefore suspected that integrins are involved in the development of endometriosis. Using immunohistochemistry, integrin expression in eutopic and ectopic endometrium is examined in endometriosis patients and control individuals. In nearly all cases, the glandular epithelial cells in the endometrium showed expression of alpha (2-), alpha (3)-, alpha (6)- and alpha (v)- integrin and a low percentage of expression of alpha (1)-, alpha (4)-, and alpha (5)-integrin. In comparison with eutopic endometrium, ectopic endometrium shows reduced expression of alpha (2)- and alpha (v)-integrin. Since no differences in alpha (2)- and alpha (v)-integrin expression were observed in eutopic endometrium between endometriosis patients and control individuals, it may be suspected that the reduced expression of these in ectopic endometrium is explained by influences in the altered environment -- e. g., in the peritoneal fluid -- on the ectopic endometrium.

Biopsy↗
PubMed2006

[Identification of preeclampsia by cDNA-gene expression profiling in human placentas and serum -- a pilot study].

OBJECTIVE: Preeclampsia is associated with significant maternal and fetal morbidity and mortality. The etiology remains unclear. For the accurate diagnosis and the prevention of preeclampsia it seems to be important to find a diagnostic tool that identifies risk patients before symptoms occur. With a new approach, the cDNA-Array analysis, human placentas and blood from preeclamptic and healthy pregnant women were examined for differentially expressed genes to find typical genes expression profiles. MATERIAL AND METHODS: In this pilot study, cDNA array analysis with a 19 200 gene array of placenta and blood samples from three preeclamptic patients have been performed to classify this samples based on expression patterns. RESULTS: Comparing normal placenta and blood from healthy delivered women (n = 4), a subset of 200 genes repeatedly found to be differentially expressed in preeclampsia. The placenta and blood samples from preeclampsia were accurately grouped by their individual gene expression patterns. CONCLUSIONS: These results suggest that the use of cDNA array is a tool to identify gene expression patterns in preeclampsia. With this set of differentially expressed genes in conjunction with sample clustering algorithms the identification of preeclampsia in placenta or blood samples is possible.

Adult↗
PubMed2006

[Cervical cancer screening of HIV-positive women: is a prolongation of the screening interval meaningful?].

OBJECTIVE: Cervical cancer screening guidelines stated recently that the screening interval of healthy women can be extended up to 3 years. Can those recommendations be applied for high risk populations? MATERIAL AND METHODS: In a prospective setting 305 HIV-positive women have been enrolled in this analysis between September 2000 and December 2003. Patients have been characterized according to HPV (human papilloma virus) prevalence, CIN (cervical intraepithelial neoplasia) incidence and CD4 cell count. RESULTS: 41 % of all HIV-positive women were HPV positive (oncogene subtypes). In patients with diminished CD4 cells the HPV prevalence increased to 60 % (54/90). CIN was found in 27 % (83/305) women. CIN was more frequent by HPV-positive women with a CD4 cell count < 200 mm (3) (52 %, 38/72). The CIN incidence was also high in HIV-positive women with negative HPV infection and diminished CD4 cell count (39 %, 7/18 vs.7 %, 11/161). CONCLUSIONS: The current cervical cancer screening guidelines are not helpful in HIV-positive women. The CIN incidence is significantly higher as in the HIV-positive population. For this reason this high risk population as e. g. HIV-infected women need an intensive care of diagnostic tools and short screening intervals to detect CIN.

Adolescent↗
PubMed2006

[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006].

This years ASCO-meeting reinforced the trend of the recent years to get off from empirical treatment concepts to tailored and individualized diagnostics and therapy. However, the basis for an individual therapy is a specific molecular diagnostic which can be reflected in the analysis of hormonal receptor, HER-1, HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only able to prognosticate the course of disease but they also can predict the success of specific treatment approaches. Trastuzumab is standard therapy in HER-2 positive breast cancer both in the adjuvant and palliative setting. But new therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2 positive breast cancer even if trastuzumab is failing. Otherwise it might possibly be an alternative option but adequate clinical results have to be awaited. The targeted inactivation of EGFR-related signal transduction pathways by e. g. gefitinib did not show a substantial improvement neither as a single agent nor in combination with endocrine treatment. However, the appropriate subgroup which might benefit from this therapy has to be defined even if molecular data suggest that patients with ER positive and PR negative breast cancer might be such a group. The increasing knowledge in terms of the biology of bone metastasis led to the development of new treatment options as e. g. denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant cytotoxic treatment trials revealed that taxanes improve the prognosis of node positive breast cancer and should be administered sequentially. The advantage of switching to an aromatase inhibitor after two to three years of tamoxifen in endocrine treatment of postmenopausal patients is proved by two clinical trials (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to be evident that new targeted therapy options are effective and will set new standards for the treatment of breast cancer patients in the near future. The presentation for the ovarian cancer focused on the addition of a third cytotoxic agent to carboplatin and paclitaxel as the standard therapy for the primary treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary and recurrent ovarian cancer were presented. However, this is not yet a standard treatment for all patients and needs further investigations within large, multicentre, randomised trials. The lymphonodectomy as part of the primary therapy of the endometrial cancer seems to be a benefit at least in patients with advanced disease or high risk stage I tumours. The adjuvant therapy of uterine sarcomas is still not yet very well investigated and clear. A trial which recruited 12 years demonstrated a benefit in overall survival which has to be interpreted with caution. In this year again there have been registered an increasing number of interesting contributions from Germany, which also received international attention.

Biomarkers, Tumor↗
PubMed2006

[Risk factors for recurrence of vulvar intraepithelial neoplasia III (VIN III)].

OBJECTIVE: The incidence of vulvar intraepithelial neoplasia (VIN) has increased in the last decades. The therapy of VIN is the in toto resection. Still some patients develop VIN recurrence. The aim of this retrospective study is the identification of risk factors for VIN recurrence. MATERIAL AND METHODS: 68 Patients with VIN III has been examined in an univariate and multivariate analysis for the following parameters (follow-up: median 27 months): age, HPV, HIV, multicentricity, resection margins (1-4 mm, 5-9 mm, > or = 10 mm). RESULTS: In the univariate analysis positive HPV and HIV status correlated with VIN recurrence. Also resection margins < 5 mm showed a significant correlation with VIN recurrence. Multivariate analysis demonstrated that HPV, HIV and resection margins < 5 mm are independent risk factors. No statistically association was found for age and multicentricity. CONCLUSION: The aim of VIN therapy must be the total resection with a negative resection margin of > or = 5 mm. HPV- and/or HIV-positive patients have a significantly higher risk for VIN recurrence and need therefore an intensive follow up.

Adult↗
PubMed2005

Radiation-induced capsule tissue reactions around textured breast implants in a rat model.

Capsule fibrosis and other complications around various filled breast implants were evaluated in a rat radiation model after 12 months of implantation. Model implants, one per rat, were implanted subcutaneously. One month after subcutaneous implantation, high voltage radiation followed one half each group. A higher rate of capsule fibrosis occurred in radiated animals. Malignant tumors at the implantation site developed in 40% of radiated and 24% of non-radiated animals, with a much higher rate of mitosis in the radiated group (Mann-Whitney, P=0.008). The presence of an implant is a cofactor for tumor development in rats (chi2-test, chi2=6.927; P=0.008) as well as radiation, since none of the control animals developed tumors. Applied to humans, capsule contracture (fibrosis) is a common complication of radiation, while development of radiation-induced sarcoma is a rare complication after postoperative radiotherapy by all account. Still further long-term follow-up human studies are necessary.

Animals↗
PubMed2005

[San Antonio Breast Cancer Symposium -- highlights 2004].

The adjuvant therapy of postmenopausal, hormonereceptor positive breast cancer patients with aromatase inhibitors in ATAC, ABCSG 8/ ARNO 95 and IES trial revealed just a benefit in terms of disease-free survival, but not for over-all survival. Thus MA-17 trial is so far the only study which could demonstrate a survival benefit for node positive disease by "extended adjuvant" therapy with letrozole. Node- and receptorpositive, postmenopausal women show a higher benefit by anthracycline containing chemotherapy in combination with tamoxifen, than by endocrine therapy alone. But tamoxifen should given sequentially to chemotherapy (Intergroup 0100/ SWOG-8814 trial). Adjuvant chemotherapy with three cycles FEC followed by three cycles docetaxel reveals a survival benefit compared to six cycles FEC, especially in women older than 50 years (PACS 01 trial). Furthermore there is evolving evidence that dose-dense, interval shortened chemotherapy is superior to standard chemotherapy in adjuvant setting. The impaired survival of receptornegative, nodalpositive breast cancer patients seems to be converted to a survival improvement compared with receptorpositive patients by modern adjuvant cytotoxic regimens (metaanalysis CALGB 8541, 9344, 9741). In primary systemic chemotherapy survival is strongly associated with the rate of pathohistological complete remissions (NSABP B-27). The combination of cytotoxic drugs has no further influence on survival, but the sequential administration of taxane increases the rate of pCR. A difference in survival stratified by pCR and non-pCR in breast and positive nodal status could not be detected, so that the number of involved lymph nodes seems to be the strongest prognostic factor and is independent of tumor response in the breast. The sentinel node biopsy is a safe and reliable method, but the rate of false negative findings depends on the pathohistological methods (NSABP B-32). The morbidity of this method is low compared with conventional axillary dissection in multicenter studies. Local tumor control is an important parameter which offers a significant survival benefit in all age cohorts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Diminished pregnancy rates in endometriosis due to impaired uterotubal transport assessed by hysterosalpingoscintigraphy.

OBJECTIVE: To investigate uterotubal transport by means of hysterosalpingoscintigraphy (HSSG) in women with and without endometriosis. DESIGN: A prospective observational study. SETTING: University Hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 350 in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles and 400 intrauterine insemination (IUI) cycles/year. POPULATION: Cases included 56 infertile women with laparoscopic proven endometriosis and patent fallopian tubes. Twenty-two women with partners suffering from male factor infertility served as controls. METHODS: A diagnostic cycle incorporating HSSG was performed. Subsequently, patients underwent either four cycles of timed intercourse (TI) or IUI in order to achieve pregnancy. If pregnancy did not occur, IVF or ICSI was performed. MAIN OUTCOME MEASURES: Evaluation of uterotubal transport capacity in women with endometriosis and healthy controls. RESULTS: Patients suffering from endometriosis (group I) showed a significant reduction in physiologic uterotubal transport function: While 20 patients (36%) had ipsi- or bilateral uterotubal transport, there was pathological uterotubal transport contralateral to the dominant follicle or a complete failure of transport capacity (negative HSSG) in 36 patients (64%). In the controls (group II), transport function was significantly different: 15 of 22 patients (68%) revealed ipsi- and bilateral tubal demonstration, while 5 patients (22%) showed contralateral transport and 2 patients (10%) showed negative HSSG (P= 0.01). Twenty-three pregnancies were observed (pregnancy rate: 29%). Eleven out of 14 (79%) women with ipsi- or bilateral tubal transport function fell pregnant by means of TI or IUI. In seven of nine patients (78%) with a failure in tubal transport, pregnancy was achieved by IVF/ICSI, despite acceptable semen parameters (P= 0.01). CONCLUSIONS: Endometriosis is significantly associated with a reduction in physiologic uterotubal transport capacity compared with controls. This resulted in diminished pregnancy rates even in women with normozoospermic partners. Therefore, IVF/ICSI may be required even when fallopian tubes are patent or semen quality is normal.

Adult↗
PubMed2005

Methylation of estrogen receptor beta promoter correlates with loss of ER-beta expression in mammary carcinoma and is an early indication marker in premalignant lesions.

The function of estrogen receptor beta (ER-beta) in mammary tissue is not completely understood. While early observations were often conflicting, more recent data suggest an important role as a tumor-suppressor gene. A decrease of ER-beta expression has been observed in ductal carcinoma in situ and invasive carcinoma as compared with benign mammary epithelial cells. The loss of ER-beta resulted in abnormal growth of mammary epithelial cells. We have previously shown that the mRNA expression of the ER-beta gene is almost totally suppressed in breast carcinomas from patients with a poor prognosis. Here we analyzed whether methylation changes in the different promoters of ER-beta are responsible for the loss of expression of the gene. A methylation assay with high specificity and sensitivity was developed, and a panel of breast tissue samples (n = 175) was characterized for methylation status. In contrast to benign breast, more than two-thirds of invasive breast cancers showed a high degree of methylation. Importantly, increased methylation was also detectable in numerous premalignant lesions. By analysis of breast tumors, previously characterized by gene-expression profiling, methylation was predominantly detected in a subgroup of patients with an unfavorable prognosis, suggesting a possible prognostic value of the ER-beta methylation status. We also investigated the structural characteristics of the two ER-beta promoters, which were both found to be closely associated with a second, downstream, localized and opposite-oriented promoter. However, we could not detect endogenous antisense RNA transcribed from these promoters, which may be involved in epigenetic gene silencing. We also failed to induce ER-beta promoter methylation by expressing siRNAs in cell lines. Interestingly, by comparing the promoter sequences of ER-beta with other genes known to be epigenetically inactivated in breast cancers, we identified a sequence motif possibly involved in promoter methylation.

Base Sequence↗
PubMed2004

Predictive value of impaired uterine transport function assessed by negative hysterosalpingoscintigraphy (HSSG).

BACKGROUND: Hysterosalpingoscintigraphy (HSSG) has given insight into the dynamics of rapid sperm transport inside the female genital tract. RESULTS: While there is an increase of an ipsilateral transport on the side bearing the dominant follicle in 70% of the subjects in the periovulatory phase, 15% of the patients do not demonstrate transport to the fallopian tubes (negative HSSG). In these patients the pregnancy rate achieved spontaneously or by intrauterine insemination is significantly reduced compared to the patients who showed an intact transport mechanism confirmed by positive HSSG. On the other hand, by means of assisted reproductive techniques (ART), pregnancy rates were higher in the group of patients showing negative HSSG (P < 0.0005). CONCLUSIONS: Our data clearly indicate that HSSG is a helpful method to evaluate the integrity of the utero-tubal transport mechanism. As pregnancy rates remain low in patients with negative HSSG, this result should be considered as an indication for IVF-treatment even in patients with patent fallopian tubes and normozoospermia of the partner.

Fallopian Tube Patency Tests↗
PubMed2004

[Sentinel lymph node biopsy in breast cancer].

Surgical treatment of breast cancer has changed dramatically during the last few decades with the aim of reducing surgical radicality in the breast and also in the axilla. In this context sentinel node biopsy is a reliable technique to determine axillary node status of breast cancer patients and reduce morbidity associated with standard axillary lymph node dissection. Although SNB is performed with increasing frequency, an incorrect indication and lack of experience with the surgical procedure can minimize the sensitivity and specificity of this method. In consequence, this could lead to wrong tumor staging and inappropriate adjuvant therapy. Therefore, we describe the basic requirements, indications, and pitfalls of this technique. Since many issues are controversial such as the prognostic value of micrometastases and extramammary nodes as well as the use of SNB after primary chemotherapy and in ductal carcinoma in situ, further clinical studies are necessary.

Axilla↗
PubMed2003

Influence of local complications on capsule formation around model implants in a rat model.

We studied the capsule formation around various filled breast implants and other related changes in distant organs (e.g., liver, spleen, lymph nodes) in a rat model 3 and 6 months after implantation. Model implants, one per rat, (filled with saline, n = 19; silicone, n = 14; cohesive silicone, n = 17; and hydrogel, n = 19) were implanted subcutaneous in the lower back of rats. The animals were sacrificed regularly after 3 and 6 months of implantation or when wound defects occurred. The capsules and organs were examined histologically, and immunohistology of the capsules was performed. A monoclonal antibody specific for AIF-1 (allograft inflammatory factor 1) was used to detect activated macrophages. Wound defects occurred most frequently after implantation of saline and hydrogel implants. Increased capsule thickness was associated with increased grade of inflammation, fibrosis, and the type of implant filling. There was a significant positive correlation between capsule thickness, presence of chronic inflammation, and AIF-1-positive macrophages (p < 0.0001), indicating that inflammation plays an important role in capsule formation. Remarkably, saline and silicone implants (in absence of local complications) cause only a blande slight fibrosis in capsules after 6 months of implantation, whereas capsules around cohesive silicone implants exhibited a more severe fibrosis with an increased capsule thickness. Most importantly, hydrogel seems to be most potent to induce an inflammatory infiltrate with AIF-1 expressing macrophages at the implantation site, independent of implantation time, and capsules also produced a significant increase in thickness after 6 months.

Animals↗
PubMed2002

The conservative management of adnexal torsion--a case-report and review of the literature.

In clinical routine adnexal torsion tends to be subject to adnexectomy to prevent embolism of thrombosed ovarian veins and its sequelae. This therapeutic intervention can be derogatory especially for young women during the reproductive years. As seen in animal models with adnexal torsion, restitution of the adnexa next to reperfusion is possible until 36 h after interruption of venous and arterial blood perfusion. We report about the successful management of a case of adnexal torsion, which was detorsed laparoscopically. We also reviewed 214 cases with conservative management of adnexal torsions reported in the literature.

Abdominal Pain↗