Biomedical subjects

P G Knapstein

Publications and source records attributed to P G Knapstein.

At least 19 recordsLinked to original sources

PubMed2003

p53 expression and resistance against paclitaxel in patients with metastatic breast cancer.

PURPOSE: Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate. MATERIAL AND METHODS: Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m(2 )either as first- (15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel. RESULTS: Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression ( n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response ( P=0.013). Expression of HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II did not show a correlation with the response to paclitaxel. CONCLUSION: The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Improved assessment of T-cell receptor (TCR) VB repertoire in clinical specimens: combination of TCR-CDR3 spectratyping with flow cytometry-based TCR VB frequency analysis.

Antigen-specific T-cell responses may be described by combining three categories: (i) the specificity and effector functions of a T-cell population, (ii) the quantity of T-cell responses (i.e., the number of responding T cells within the CD4/CD8 population), and (iii) the "quality" of T cells (defined by the T-cell receptor [TCR] structure). Several methods to measure T-cell responses are now available including evaluation of T-cell precursors using limiting dilution, the enzyme-linked immunospot assay, ex vivo TCR variable (v)-segment analysis determined by flow cytometry, and TCR-CDR3 length analysis (spectratyping), as well as identification of peptide-specific T cells using major histocompatibility complex (MHC) class I tetramers containing appropriate peptides. Until now, only a limited set of MHC-peptide complexes have been available as tetramer complexes. We demonstrate that CD8(+) or CD4(+) T cells in patients with cancer can be molecularly defined using a combination of spectratyping (TCR structure and "molecular composition") plus the implementation of an antibody panel directed against 21 individual VB TCR chains ("quantity" of T-cell families). This approach is instrumental in defining and comparing the magnitudes of CD4(+) or CD8(+) T-cell responses over time in individual patients, in comparing the TCR VA and VB repertoire in different anatomic compartments, and in comparing the TCR VA-VB diversity with that in normal healthy controls. This method provides the means of objectively defining and comparing the TCR repertoire in patients undergoing vaccination protocols and underlines the necessity to calibrate the TCR-CDR3 analysis with a qualitative assessment of individual TCR VB families.

CD4-Positive T-Lymphocytes↗

PubMed2002

Antigen-driven T-cell selection in patients with cervical cancer as evidenced by T-cell receptor analysis and recognition of autologous tumor.

We characterized the T-cell receptor (TCR) repertoire in freshly harvested tumor lesions, in short-term-expanded CD4(+) tumor infiltrating lymphocytes (TIL) as well as in CD4(+) and CD8(+) peripheral blood lymphocytes (PBL) from three patients with cervical cancer. Skewing of the T-cell repertoire as defined by measuring the length of the complementarity-determining region 3 (CDR3) of the TCR VA and VB chains was observed in CD8(+) PBL, in freshly harvested tumor tissue, as well as in CD4(+) TIL. Comparative analysis of the TCR repertoire revealed unique monoclonal TCR transcripts within the tumor lesion which were not present in PBL, suggesting selection of TCR clonotypes due to antigenic stimulation. TCR repertoire analysis of the short-term (7-day) CD4(+) TIL lines revealed that the TCR composition is markedly different from that in CD4(+) PBL or in the freshly harvested tumor tissue. Only one-third of CD4(+) TIL lines showed HLA-DR-restricted recognition of autologous tumor cells as defined by cytolysis. These data provide support for the antigen-driven selection of T cells within cervical cancer lesions and suggest that analysis of the TCR repertoire may aid in obtaining an objective description of the immune response in patients with cervical cancer who are undergoing epitope-based immunotherapy.

Antigens, Neoplasm↗

PubMed2001

Metallothionein expression in ovarian cancer in relation to histopathological parameters and molecular markers of prognosis.

Metallothioneins (MTs) and glutathione constitute the major fractions of intracellular thiol factors. Abundant nucleophilic sulfhydryl groups can interact with many electrophilic substances, including several anti-neoplastic agents, participate in controlling intracellular redox potential, and act as scavengers of reactive oxygen species. In the present study, we examined the relation of MTs (alone and in combination with glutathione) to histopathological parameters and survival time of ovarian cancer patients. Expression of the major MT isoforms (MT-1 and MT-2) was determined by immunohistochemistry on paraffin-embedded tumor specimens from 189 patients, 151 suffering from primary epithelial ovarian cancer and 38 from recurrences. MT was negatively associated with survival time when all patients with primary carcinomas (n = 151) were analyzed (p = 0.049, log-rank test). However, no significant association between MT expression and survival was obtained when subgroups of patients with histological grade 1, 2 or 3 carcinomas were analyzed. Similarly, no significant association of MT expression and survival was obtained with the proportional hazards model adjusted for histological grade. This scenario can be explained by a correlation between MT expression and histological grade: MT was detectable in 26%, 48% and 62% of grade 1, 2 and 3 carcinomas, respectively (p = 0.008, chi(2) test). An interesting hypothesis is generated by combined analysis of MT and total glutathione content (GSH). The product of MT and GSH levels (MT x GSH) was negatively associated with survival of grade 1 carcinomas (p = 0.021, log-rank test) but not with grade 2 and 3 carcinomas (p = 0.176 and 0.403, respectively). When MT x GSH was greater than the median, 25% of patients with grade 1 carcinomas died within 235 days. In contrast, all patients with grade 1 carcinomas survived when MT x GSH in tumor tissue was smaller than the median. This suggests that high expression of sulfhydryl factors might facilitate survival and progression of low-grade ovarian cancer cells. A significant correlation was obtained between MT expression and mutant p53 (p = 0.037, chi(2) test). However, this might be an indirect effect since both MT (p = 0.008) and mutant p53 (p = 0.000) were associated with histological grade. In conclusion, MT expression as well as the product of MT and GSH were associated with histological grade of primary ovarian carcinomas. High expression of both sulfhydryl factors may identify a subgroup of low-grade carcinomas with an increased risk of progression.

Disease Progression↗

PubMed2001

Perineal excision of a large angiomyxoma in a young woman following magnetic resonance and angiographic imaging.

BACKGROUND: Aggressive angiomyxomas are rare, arise from connective tissue of the perineum or the lower pelvis, and affect predominantly young women. CASE: We describe an unusual case of aggressive angiomyxoma in which the perineal approach was possible owing to MRI scanning and selective angiography indications. CONCLUSION: In cases of large aggressive angiomyxomas these diagnostic procedures should make it possible to decide which operative route might be best for the patient.

Adult↗

PubMed2001

[Integrated gynecology: new medical treatments due to psychosomatic methods of evaluation].

OBJECTIVE: Women with gynecologic cancer are confronted with difficult decisions regarding the therapeutic options. The objective of the present paper is to demonstrate the relationship between surgical procedures and the outcome on quality of life and to discuss the implications for patient management. METHODS: Gynecologic patients were assessed in a prospective study with preoperative semistructured interviews and objective assessments (T1), interviews were repeated 4 and 12 months postoperatively (T2, T3). RESULTS: Women planned for hysterectomy with severe complaints indicate a better postoperative quality of life. Cancer patients, however, tend to feel more distressed about the surgical procedure if they could not be treated organ preserving or by reconstructive techniques. Medical interaction is dependent on the patient's anxiety level and mostly important for their quality of life before and after surgery. CONCLUSION: Psychosomatic research is not only necessary to understand the patient's needs before and after surgery but may also serve as an evaluation method of therapeutical options. By this methods we are able to anticipate the medical and psychological consequences of the therapeutic decisions. Future studies will systematically explore the alternating effect of surgical procedures on the patient's well-being.

Female↗

PubMed2001

[Body image in gynecologic patients before and after radical surgery].

After radical gynecologic surgery women are faced with therapy-induced changes of their body. Since 1995, the body images of women who undergo pelvic exenteration, Wertheim-Meigs-operation or hysterectomy are assessed preoperatively and four and twelve months postoperatively. The aim of this multidimensional prospective study is to get basic information for effective counselling and support. One year after hysterectomy women state to have a normal body image. Cancer patients feel less attractive, less self-confident and more discontented in sexuality depending on therapy-induced changes of their bodies. These women could profit from problem-related preoperative counselling. Postoperative counselling offers will be helpful to support women in the process of acceptance of bodily changes and in the reorganisation of their sexual life.

Body Image↗

PubMed2001

Human papillomavirus (HPV) DNA in primary cervical cancer and in cancer free pelvic lymph nodes--correlation with clinico-pathological parameters and prognostic significance.

OBJECTIVE: To assess whether the presence of human papilloma virus (HPV) DNA and/or several genotypes of HPV DNA in primary cervical cancer and cancer free pelvic lymph nodes are correlated with several clinicopathological parameters of well-defined prognostic significance and whether virological parameters are predictors of long-term survival in cancer patients. PATIENTS AND METHODS: 223 cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the high sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathological parameters and survival data. RESULTS: HPV DNA was detected by PCR in 150 of 203 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histological tumor types, node status, blood vessel invasion and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox Regression Analysis (RR 2.856, p < 0.003 resp. RR 3.444, p < 0.0001). The presence of HPV DNA in cancer free pelvic lymph nodes was significantly correlated to the concomitant manifestation of pelvic lymph node metastases (RR 3.1, p < 0.0001). In the multivariate analysis, however, HPV DNA in primary tumor and in negative pelvic lymph nodes failed to be of prognostic relevance. Exclusively, HPV 16 appears to impact independently on the overall survival in cervical cancer patients (RR 3.653, p < 0.002). CONCLUSION: The detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors and cancer free pelvic lymph nodes remains to be investigated in further studies. The exact mechanisms by which HPV influence the prognosis of cervical cancer patients have to be defined.

Adenocarcinoma↗

PubMed2001

[Personal Digital Assistants assisting in clinical and administrative tasks].

Personal digital assistants (PDAs) are increasingly used by many professional and private users. They replace and combine common calendars, directories, to-do-lists and much more. Supplemented by useful additional software they can assist the clinician in his daily routine work. This concerns typical medical information as well as administrative work but gets more importance with regard to the planned introduction of diagnosis related groups in Germany however. Exact coding of medical performance is essential for this future invoice system. How PDAs can be used convenient in this respect will be shown with examples from our department.

Diagnosis-Related Groups↗

PubMed2001

[Endometrial carcinoma in patients with diabetes mellitus].

OBJECTIVE: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - MATERIAL AND METHODS: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a chi(2)-test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independence. - RESULTS: The mean follow-up period was 49 months. The mean age was 65 years. 21.8 % of the patients had an additional diabetes mellitus. These patients had a significantly deeper infiltration of the Myometrium (p-value = 0.004) and were more likely to have lymphonode metastasis (p-value = 0.02). - CONCLUSION: Our results show a correlation between Diabetes mellitus and adverse prognostic factors witch affects by the rate of lymphonode spread and overall survival.

Aged↗

PubMed2000

(A)symptomatic necrotizing arteritis of the female genital tract.

AIMS: The vasculitides represent a heterogenous set of disorders that differ in prognosis and response to therapy. Beside systemic vasculitides, the development of localized forms of arteritis is well known though uncommon and the etiopathogenesis is not yet definitely clear. METHODS: Patients with necrotizing arteritis of the female genital tract proven by histology are studied in a retrospective analysis. RESULTS: Three cases of necrotizing arteritis with histological features of panarteritis nodosa apparently confined to the female genital tract are presented. None of these patients had prior history of systemic vasculitis. The acute necrotizing vasculitis was confined only to the uterine cervix in two patients and involved all the internal genital organs in the third patient. The patients have been observed for up to 4 years without any therapy for these lesions and without any manifestation of systemic vasculitic progression. CONCLUSION: It is to speculate that focal arteritis of the female genital tract is a benign form of panarteritis nodosa or moreover a totally different entity with identical morphogenesis but possibly different pathogenesis. Furthermore it seems to be important to be aware of the specificity of focal arteritis in female genital tract as distinct from the generalized form to prevent unnecessary surgical or chemotherapeutical therapy for this lesion. The benign entity of local arteritis in the female genital tract is discussed in contrast to the severe prognosis of systemic panarteritis nodosa.

Aged↗

PubMed2000

[Integration of quality assurance procedures into medical documentation systems--from quality indicator to improved medical quality].

Medical and commercial data are essential for sufficient clinical management. While regional quality studies--for example the German Perinatal Data Study--are mighty tools to compare the quality of departments in total--the integration of evaluated individual quality indicators in data processing systems can highly improve clinical results and clinical management. The evaluation of quality indicators improves the benefit of quality management. Parameters monitoring the contentment of patients are extremely valuable information. Quality management and information management are closely linked.

Data Collection↗

PubMed2000

[Medical controlling--principles, conditions and current tools].

In 2003 diagnosis related groups (DRG's) will be established in Germany as a new system for describing costs of inpatient treatment. Principles of medical controlling are explained, the development from the system formerly used in Germany towards DRG's is described and computer-based assistance already available is pointed out and evaluated critically.

Diagnosis-Related Groups↗

PubMed1999

Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer.

Overexpression of the c-erbB-2 (HER-2/neu) oncogene, which encodes a transmembrane receptor tyrosine kinase, has been shown to be associated with poor prognosis in ovarian and breast cancer. Recent studies indicate that c-erbB-2 may also be involved in determining the chemosensitivity of human cancers. In the present study, we examined the role of c-erbB-2 for chemoresistance in ovarian cancer. Overexpression of c-erbB-2 mRNA in tumor tissue was associated with a shorter survival of patients with primary ovarian cancer (P = 0.0001; n = 77) and was an independent prognostic factor in the proportional-hazard model adjusted for International Federation of Gynecologists and Obstetricians stage, residual disease, chemotherapy, and age (P = 0.035). A significant association between expression of c-erbB-2 mRNA and survival was obtained for the subgroup of patients who received a standard chemotherapy with carboplatin or cisplatin and cyclophosphamide (P = 0.0003), whereas only a nonsignificant trend was observed for patients who did not receive a standard chemotherapy (P = 0.124). In addition, the application of a standard chemotherapy improved the survival of patients with relatively low c-erbB-2 expression (P = 0.013) but not of patients with overexpression of c-erbB-2 (P = 0.359). Expression of c-erbB-2 mRNA correlated with expression of topoisomerase IIalpha mRNA determined by a reverse semiquantitative PCR technique (P = 0.009), whereas expression of c-erbB-2 and topoisomerase IIbeta mRNA did not correlate (P = 0.221). To examine the hypothesis that coamplified and/or coregulated topoisomerase IIalpha contributes to the resistance of c-erbB-2-overexpressing carcinomas, we established a chemosensitivity assay using primary cells from an ovarian carcinoma that overexpressed both c-erbB-2 and topoisomerase IIalpha. The combination of carboplatin with nontoxic concentrations of the topoisomerase II inhibitors etoposide or novobiocin enhanced the toxicity of carboplatin. In contrast, the tyrosine kinase inhibitor emodin exhibited no chemosensitizing effect in cells of this individual carcinoma. In conclusion, overexpression of c-erbB-2 was associated with poor prognosis and poor response to chemotherapy. The data suggest that topoisomerase IIlalpha, which correlates with c-erbB-2 expression, contributes to the resistance of c-erbB-2-overexpressing carcinomas.

Antigens, Neoplasm↗

PubMed1999

Ovarian endometrioid-like yolk sac tumor treated by surgery alone, with recurrence at 12 years.

We describe the case of a stage Ia endometrioid-like yolk sac tumor (YST) of the ovary, which was originally misdiagnosed as a malignant struma ovarii and not treated with adjuvant chemotherapy. After 12 years, a contralateral dermoid cyst was excised along with a small omental nodule of partially necrotic and calcified endometrioid-like YST. No tumor was detected in several other biopsy specimens, and a peritoneal lavage was negative for tumor cells. Since there was no evidence of remaining tumor and the serum alpha-fetoprotein (AFP) level was normal after the second operation, the patient was followed. Serial serum AFP levels remained normal for 4 months. At a second-look laparotomy after 4 months, a small tumor nodule was removed from the cul-de-sac. Postoperatively, the patient received three cycles of BEP chemotherapy. The long disease-free interval after the first operation in spite of the presence of occult spread to the omentum and to the pouch of Douglas in this case indicates that some endometrioid-like YSTs may have an indolent course. The present case underscores the importance of careful surgical staging and of long-term follow-up in cases of primitive germ cell tumors of the ovary.

Adult↗

PubMed1999

Expression of tenascin in human cervical cancer--association of tenascin expression with clinicopathological parameters.

OBJECTIVE: Tenascin is an extracellular matrix glycoprotein, relevant for embryonal and fetal development, which is reexpressed in the stroma of benign and malignant tumors. Little is known about the molecular interaction of tenascin during neoplastic transformation and tumor progression in cervical cancer. METHOD: We studied the expression of tenascin in normal tissue of the cervix uteri, cervical carcinoma in situ, and invasive cervical carcinoma in paraffin sections by immunohistochemistry using a monoclonal antibody. Tenascin immunoreactivity was compared with various prognostic parameters. RESULTS: In normal cervical tissue (n = 5) and in cervical carcinoma in situ (n = 10) only vessel walls showed a weak tenascin cross-reactivity, whereas tenascin was not expressed in the epithelial layer or the underlying connective tissue. In invasive cervical carcinoma (n = 89) tenascin expression was markedly increased. In 84% (n = 75) of the cases examined a strong tenascin immunoreactivity was noted around and within the tumor cell nests. Sixteen percent (n = 14) of infiltrating cervical carcinomas showed no tenascin immunoreactivity. A definite correlation was found between weak or no tenascin expression and slight desmoplastic mesenchymal reactivity (n = 42/91%, P < 0.001), lymphatic space invasion (n = 54/81%, P < 0.001), and lymph node metastases (n = 30/77%, P < 0.05). Tenascin-positive patients had a significantly better prognosis than tenascin-negative patients (mean survival time of 56.5 +/- 4.1 months versus 31.9 +/- 5.6 months, P < 0.05). CONCLUSION: Based on these findings we discuss that the appearance of tenascin is an indicator of an adequate biological defense in cervical cancer patients. The tenascin staining may therefore be useful for detecting a subgroup of invasive cancer patients missing tenascin reactivity with alterations of stromal defense and a poorer prognosis.

Carcinoma in Situ↗

PubMed1999

Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival.

Since detailed knowledge regarding the pathophysiological properties which in turn are responsible for differences in contrast enhancement--remain fairly undetermined, it was the aim of this study (i) to examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis (microvessel density [MVD]; vascular endothelial growth factor [VEGF]); and (ii) to determine the ultimate value of a histomorphological and a dynamic MRI approach by correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, exchange rate constant k21) and standard parameters (maximum signal intensity (SI)-increase [SI-I] over baseline and steepest SI-upslope per second [SI-U/s]) were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with similar sized and positioned regions-of-interest (ROIs) on the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and amplitude A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between the VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05, 0.001, respectively) worse disease outcome than tumors with low k2, and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD, VEGF) had any significant power to predict patient survival. It is concluded that (1) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF-expression; (2) a functional, dynamic MRI approach (both standard and a pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis; and [3] compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.

Adult↗

PubMed1999

[Value of clinically established MRI procedures concerning the pretherapeutic evaluation of maximal tumor diameter in primary or recurrent cervix cancer in relation to palpation findings and histopathologic whole mount specimens].

OBJECTIVE: The maximal tumor diameter of cervical cancer is one of the most important prognosis factors concerning patients' survival. The purpose of this study was to investigate the efficiency of different MRI-procedures in relation to clinical palpation concerning pretherapeutic tumor diameter assessment. MATERIAL AND METHODS: Thirty-one patients with biopsy proven primary cervical cancer and its recurrence (n = 10), respectively, underwent dynamic and conventional MRI before further treatment. The results of maximal tumor diameters were compared to palpatory findings and then correlated to the whole mount specimen as gold standard. RESULTS: The contrast-enhanced dynamic and T2-weighted MRI allows a significantly better (p < 0.05) assessment of maximal tumor diameter of cervical cancer than the conventional T1-weighted MRI. The T2-weighted MRI showed the highest correlation (r = 0.83) in respect to the whole mount specimen up to FIGO-IIB disease. The contrast-enhanced dynamic MRI and the palpation were characterized by the highest correlation coefficients of r = 0.77, r = 0.70 respectively, in advanced cervical cancer > FIGO-IIB disease. CONCLUSIONS: The MRI procedures offer no evident advantage in relation to clinical palpation to determine the maximal tumor diameter of cervical cancer or its recurrency and seems not to be indicated generally.

Adult↗