Biomedical subjects

R Kurek

Publications and source records attributed to R Kurek.

28 records · Page 2Linked to original sources

PubMed1999

Intermittent complete androgen blockade in PSA relapse after radical prostatectomy and incidental prostate cancer.

OBJECTIVES: To determine the efficacy, safety and feasibility of intermittent androgen deprivation (IAD) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy or with an incidental prostate cancer (pT1B) after transurethral resection of the prostate (TURP). METHODS: Open, nonrandomized, prospective pilot study using the luteinizing hormone-releasing hormone analogue (LH-RHa), leuprorelin acetate (1-month depot) and cyproterone acetate. RESULTS: Forty-four patients have been enrolled. After a 30-64 months' follow-up no progression to androgen-independent status has been observed. Of the entire observation period, 26.6 months (44-58%) remained treatment-free. During the treatment-free periods, normal testosterone levels were obtained, resulting in a cessation of the symptoms of androgen suppression and an improvement in quality of life. CONCLUSIONS: These results indicate that IAD is an effective and feasible therapy in patients with early stages of prostate cancer. Larger trials are necessary to confirm these encouraging results. Therefore, a European prospective, randomized, multicenter study (RELAPSE study) has been started to compare IAD with continuous androgen blockade in terms of time to tumor progression, safety and quality of life in patients with PSA relapse after radical prostatectomy.

Aged↗

PubMed1999

Spectrum of mammographically detected breast cancers.

Mammographic screening of women at both ends of the age spectrum presents a number of challenges. The purpose of this study was to characterize experience with mammographic detection of breast cancer. The two goals were 1) to establish the cancer detection rate of screening mammography and 2) to compare the tumor size of cancers found by mammography, physical examination, or both modalities. From January 1994 through June 1997, data on 609 consecutive female primary breast cancer patients were collected concurrent with definitive surgical therapy. The method of detection was determined by the surgeon, after reviewing mammogram and physical examination. Screening ultrasound was not used. For the 184 patients under 50 years of age, 53 (29%) cancers were detected by mammography only and 48 (26%) by physical examination only. Women under 50 years of age had fewer cancers detected by mammography only (P < 0.001) and more cancers detected by physical examination only (P = 0.0014) than those over 50. With increasing age, the proportion of women with ductal carcinoma in situ decreased (P = 0.004), and the proportion with T1c or T2 tumors increased (P = 0.006). We conclude that 1) when examining women under 50 years of age, the surgeon must be clearly focused on the double-edged sword of screening mammography in this age group, and 2) community cancer programs should encourage annual screening of women over 40 years of age but focus on those over 70, without an arbitrary upper age limit.

Adult↗

PubMed1998

The Y chromosomal fertility factor Threads in Drosophila hydei harbors a functional gene encoding an axonemal dynein beta heavy chain protein.

To understand the contradiction between megabase-sized lampbrush loops and putative protein encoding genes both associated with the loci of Y chromosomal fertility genes of Drosophila on the molecular level, we used PCR-mediated cloning to identify and isolate the cDNA sequence of the Y chromosomal Drosophila hydei gene DhDhc7(Y). Alignment of the sequences of the putative protein DhDhc7(Y) and the outer arm dynein beta heavy chain protein DYH2 of Tripneustes gratilla shows homology over the entire length of the protein chains. Therefore the proteins can be assumed to fulfill orthologous functions within the sperm tail axonemes of both species. Functional dynein beta heavy chain molecules, however, are necessary for the assembly and attachment of outer dynein arms within the sperm tail axoneme. Localization of DhDhc7(Y) to the fertility factor Threads, comprising at least 5.1 Mb of transcriptionally active repetitive DNA, results from an infertile Threads- mutant where large clusters of Threads specifically transcribed satellites and parts of DhDhc7(Y) encoding sequences are missing simultaneously. Consequently, the complete lack of the outer dynein arms in Threads- males most probably causes sperm immotility and hence infertility of the fly. Moreover, preliminary sequence analysis and several other features support the hypothesis that DhDhc7(Y) on the lampbrush loops Threads in D. hydei and Dhc-Yh3 on the lampbrush loops kl-5 in Drosophila melanogaster on the heterochromatic Y chromosome of both species might indeed code for orthologous dynein beta heavy chain proteins.

Amino Acid Sequence↗

PubMed1998

Intermittent Complete Androgen Blockade in PSA Relapse after Radical Prostatectomy and Incidental Prostate Cancer.

Objectives: To determine the efficacy, safety and feasibility of intermittent androgen deprivation (IAD) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy or with an incidental prostate cancer (pT1B) after transurethral resection of the prostate (TURP). Methods: Open, nonrandomized, prospective pilot study using the luteinizing hormone-releasing hormone analogue (LH-RHa), leuprorelin acetate (1-month depot) and cyproterone acetate. Results: Forty-four patients have been enrolled. After a 30-64 months' follow-up no progression to androgen-independent status has been observed. Of the entire observation period, 26.6 months (44-58%) remained treatment-free. During the treatment-free periods, normal testosterone levels were obtained, resulting in a cessation of the symptoms of androgen suppression and an improvement in quality of life. Conclusions: These results indicate that IAD is an effective and feasible therapy in patients with early stages of prostate cancer. Larger trials are necessary to confirm these encouraging results. Therefore, a European prospective, randomized, multicenter study (RELAPSE study) has been started to compare IAD with continuous androgen blockade in terms of time to tumor progression, safety and quality of life in patients with PSA relapse after radical prostatectomy.

Journal Article↗

PubMed1996

Strukturdifferenzierungen in Y-chromosom von Drosophila hydei: the unique morphology of the Y chromosomal lampbrush loops Threads results from 'coaxial shells' formed by different satellite-specific subregions within megabase-sized transcripts.

The results of pulsed-field gel electrophoresis (PFGE) analysis and two-colour transcript fluorescence in situ hybridization (FISH) for the three Threads-specific DNA satellites YLII, YLI and rally are in support of long-range clustering of these sequence families within the subterminal region on the long arm of the Y chromosome of Drosophila hydei. On the basis of the linear arrangement of at least four extended clusters of satellite-specific sequences, the loop morphology of wild-type and several mutant Threads can be explained by assumption of a single Threads-specific transcription unit comprising about 5.1 Mb of repetitive DNA located between the Pseudonucleolus and the Nucleolus organizer. Transcription is unidirectional from the Pseudonucleolus towards the terminally located Nucleolus organizer. Transcripts most likely start in front of or within the 3.2 Mb region of YLII-related sequences, pass through subsequent blocks of 1.2 and 0.3 Mb of YLI- and rally-related sequences, respectively, and cease within the region of a smaller block of YLI-related repeats. The megabase-sized transcripts remain physically linked to the DNA axis and their extended satellite-specific regions form coaxial clouds or shells around the central DNA axis. In this way each cluster of earlier-transcribed sequences generates a cloud or shell on top of the later-transcribed ones. According to this model of 'satellite-specific coaxial shells' the tube-like morphology and other peculiarities of the Y chromosomal lampbrush loops Threads can be explained as a result of satellite-specific RNA superstructures and/or formation of extended ribonucleoprotein (RNP) complexes between clusters of satellite-specific transcripts and specific proteins. On the basis of this model the specific morphology of several Threads mutants can be interpreted as the result of large interstitial or terminal deletions that alter the total length of the Threads-specific transcription unit without exerting other major effects on principal features of the transcription process along the Threads.

Animals↗

PubMed1996

[Laparoscopy in (apparently) benign ovarian tumors between benefit and catastrophy and the deceptive safety of laparoscopic lap sacs].

Endoscopic ovarian surgery is currently spreading tremendously, but also rather uncritically. The technical possibilities both of organ preserving and ablative endoscopic surgery are controversial, so that structuring of the indication for an endoscopic procedure as well as optimization of the endoscopic removal of ovarian tumor or adnexae is of utmost relevance. Therefore, a study was performed at the Department of Obstetrics and Gynaecology of the Heidelberg University with the following aims: Risk evaluation of operating into an ovarian malignancy at endoscopy for "presumably" benign cystic ovarian tumors in n = 100 cases in Heidelberg and literature survey Analysis of problems and complications during clinical application of laparoscopic lap sacs for removal of cystic adnexal tumors or adnexae (n = 50) Experimental examination of the risk of an endoscopic lap sacs to rupture during a procedure The risk of endoscopically operating into an ovarian cancer lies between 0.4 and 3% according to literature data. Despite maximal preoperative selection, mainly by ultrasound examination, in our group of 100 patients, in three women without preoperative signs of malignancy but with discreet intracystic structures in the ultrasound, an endoscopic adnexectomy with complete removal in a lap sac was performed, and though immediate section for microscopic examination was negative, final histology revealed one ovarian cancer la and 2 borderline tumors, same stage. In the time period analyzed, three further patients were referred to our center for secondary, delayed (median 3 months) staging after endoscopic procedures for presumed benign lesions. Clinical application of lap sacs proved the necessity of an intensive training. In 3 patients an intraperitoneal rupture of the sac occurred. Typical problems were volume discrepancies between sac respectively abdominal incision and tissue to be removed (28% of cases). The risk of rupture of the various lap sacs examined differed significantly (p < 0.05). Due to the complex pathological nature of cystic adnexal tumors, a 100% selection for the endoscopic approach is not feasible. Therefore, an endoscopic procedure should only be performed after optimal preoperative diagnosis and, in case of the slightest doubt, only if intraoperative microscopic examination is available, and the possibility to perform an immediate staging laparotomy. Sufficient information of the patient is relevant. Laparoscopic removal of tumor or adnexae should be performed in a lap sac. However, there is no absolute certainty of preventing spillage even with the lap sac, since not all endoscopic sacs available are of a sufficient quality.

Adult↗

PubMedDate not supplied

Treatment of the twin-twin transfusion syndrome: initial experience using laser-induced interstitial thermotherapy.

This paper describes our initial experience with laser-induced interstitial thermotherapy (LITT) for the treatment of the twin-twin transfusion syndrome (TTTS). This procedure was utilized in four pregnancies-three monochorionic twin pregnancies and one triplet pregnancy (20-26 weeks of gestation)-with severe TTTS with fetal dropsy, polyhydramnion of the acceptor, and anhydramnion of the donor. In vitro examinations of placental tissue had shown that laser coagulation can be monitored by sonography, hence we used this method for the first time in these four pregnancies. Blood vessels connecting the two umbilical cords were determined prior to the treatment using a new ultrasound color technique which is highly sensitive and capable of representing slow blood flow velocities. A 1.2 mm thick puncture needle was then directed to the shunt under on-line ultrasound control. All patients had an anterior wall placenta. The laser fiber was inserted via this thin needle. A coagulation time of 2-3 min was necessary at 3 W. In the one twin pregnancy the intrauterine fetal death of the smaller child occurred 10 weeks after LITT, the other child survived and is healthy. A cesarian section was necessary in another twin pregnancy 1 week after LITT due to the intrauterine death of the smaller child. In the third twin pregnancy, the donor, who had already had distinct bradycardia prior to the treatment, died immediately after LITT. The intrauterine fetal death of the donor in the triplet pregnancy occurred 3 days after LITT once the volume of amniotic fluid had basically returned to normal. The tragic intrauterine death of the uninvolved child occurred 13 weeks later as a result of umbilical cord strangulation, the surviving child is healthy. All four pregnancies were severe and advanced cases of TTTS with a very poor prognosis, leaving us with no other alternative to the described method of treatment. The instruments we used are a lot thinner than those utilized for fetoscopic laser treatment to date. Furthermore, it is not necessary to penetrate the amniotic sac in patients with an anterior wall placenta; intraplacental vessels can be coagulated, and the laser energy required for LITT is also much lower. In our opinion these advantages justify the utilization of LITT under more promising conditions than those described above.

Adult↗

PubMedDate not supplied

Influence of tumor biological factors on tumor cell dissemination in primary breast cancer.

BACKGROUND: The presence of disseminated tumor cells in the bone marrow (BM) of breast cancer patients is associated with poor prognosis and may therefore be related to aggressive breast cancer as indicated by tumor biological and clinicopathological factors. The aim of this study was to identify those features of the primary tumor related to the presence of disseminated tumor cells in the BM. PATIENTS AND METHODS: Clinical data from 508 primary breast cancer patients were analyzed. Tumor biological features of the primary tumor including HER2, p53, Ki-67, bcl-2 and hormone receptor status, as well as clinicopathological factors including histology, menopausal status, lymph node status, tumor size and grade, were studied for their association with BM involvement by univariate and multivariate analysis. RESULTS: Two-hundred and two out of 508 (40%) primary breast cancer patients had disseminated tumor cells in the BM. p53 expression, hormone receptor status, HER2 and Ki-67 were significantly related to BM involvement. The multivariate analysis revealed that p53 expression (OR: 1.9, 95% CI: 1.2 - 3.0) followed by progesterone receptor status (OR: 1.5, 95% CI: 1.0 - 2.2) were the only independent determinants for BM involvement. CONCLUSION: The presence of disseminated tumor cells in the BM was not influenced by tumor load as reflected by tumor size and lymph node involvement, whereas tumor biological factors were independently correlated to BM involvement. The results substantiate the important role of tumor biological factors of the primary tumor for tumor cell dissemination.

Bone Marrow↗

PubMedDate not supplied

Changes of serum HER2 status during clinical course of metastatic breast cancer patients.

BACKGROUND: Serum HER2 testing allows the determination of the real-time HER2 status of breast cancer patients. The aim of this investigation was to study (i) whether changes of serum HER2 status occur during the clinical course of breast cancer and (ii) to evaluate the prognostic significance of serum HER2 status, at the time of first diagnosis of primary breast cancer and at the onset of metastatic disease, for survival after relapse (SAR). MATERIALS AND METHODS: HER2 serum levels were retrospectively measured in 152 breast cancer patients at the time of first diagnosis of breast cancer and at the onset of metastatic disease by enzyme immunoassay. RESULTS: Twenty-seven out of 152 (18%) patients had elevated HER2 serum levels at the time of first diagnosis of breast cancer. In contrast, 56 out of 152 (37%) patients showed elevated serum HER2 levels when metastases were diagnosed. A change of serum HER2 status during clinical course was observed in 43 out of 152 (28%) patients. Serum HER2 status at the time of first diagnosis of breast cancer had no impact on survival after relapse (SAR) (p = 0.4). However, the median SAR for serum HER2-positive patients at the onset of metastatic disease was significantly shorter (8 months, 95% CI: 3-12) compared to patients serum HER2-negative at this time (18 months, 95% CI: 14-22) (p < 0.01). CONCLUSION: Serum HER2 status can change during the course of disease. Therefore, the serum HER2 status should be re-evaluated at the time of diagnosis of metastatic disease to optimize treatment decisions.

Breast Neoplasms↗

PubMedDate not supplied

Her-2/neu expression in breast cancer--A comparison of different diagnostic methods.

BACKGROUND: Determination of Her-2/neu overexpression in breast cancer has previously been shown to be of prognostic significance. In this study, Her-2/neu expression in breast cancer was characterised by real-time PCR (RLT-PCR) based LightCycler-HER-2/neu DNA Quantification with immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). MATERIAL AND METHODS: Fifteen specimens of invasive breast cancer - whole tissue sections as well as microdissected tumour cells - were subjected to RLT-PCR. Additionally, IHC and FISH were performed. RESULTS: Her-2/neu overexpression was detected by FISH and by real-time PCR in the same tumours. In contrast, IHC revealed discordant results. CONCLUSION: Determination of Her-2/neu amplification by real-time PCR is a sensitive and specific method with some advantages over FISH. This method is simple and reliable and has the potential of categorizing those tumours with borderline Her-2/neu overexpression as determined by IHC.

Breast Neoplasms↗