Search PubMed⌕ Search

Biomedical subjects

H P Sinn

Publications and source records attributed to H P Sinn.

At least 19 recordsLinked to original sources
PubMed2000

Stage IIa cervix carcinoma with metastasis to the heart: report of a case with immunohistochemistry, flow cytometry, and virology findings.

OBJECTIVE: The aim of this study was to report a stage IIa squamous cell cervix carcinoma with intraperitoneal carcinomatosis and metastasis to the heart in a 50-year-old woman and to study the original tumor for expression of oncogenes and tumor suppressor gene proteins, for DNA ploidy, and for human papillomavirus (HPV) infection. METHODS: Clinical course, histopathology of the original tumor, and autopsy record were rewieved. The original tumor was analyzed for expression of CD44 variant 6, p16, p21, p53, retinoblastoma (Rb), and c-erb-2. DNA flow cytometry was performed on tissue samples from the original tumor and from the heart. Sequences of the HPV genome on cervical and cardiac tissue samples were amplified by polymerase chain reaction. RESULTS: Immunohistochemical analysis showed expression of CD44v6 and p16. No expression of p21, Rb, c-erb-B2, and p53 was seen. DNA flow cytometry of the original cervical tumor showed a DNA index (DI) of 1.0. DNA flow cytometry of tissue samples from the posterior wall and from the right ventricle of the heart showed two different aneuploid cell populations with DI of 1.6 and 2.2, respectively. HPV gene sequences were identified neither in the original tumor nor in the heart. CONCLUSIONS: To our knowledge, this is the first case of cervix carcinoma with metastasis to the heart with immunohistochemistry, flow cytometry, and virology findings.

Carcinoma, Squamous Cell↗
PubMed1999

Pathophysiologic basis of contrast enhancement in breast tumors.

While the diagnostic benefits of gadolinium (Gd)-chelate contrast agents are firmly established in magnetic resonance imaging (MRI) of tumors, the pathophysiologic basis of the enhancement observed and its histopathologic correlate remained vague. Tumor angiogenesis is fundamental for growth and metastasis and also of interest in new therapeutic concepts. By correlative analysis of a) histology; b) vascular density (CD31); and c) vascular permeability (vascular permeability factor/vascular endothelial growth factor [VPF/VEGF]), we found a) significantly (P < 0.001) faster exchange rates in malignant compared with benign breast lesions; b) distinct differences in enhancement characteristics between the histologic types (invasive ductal carcinoma, invasive lobular carcinoma, and ductal carcinoma in situ); and c) dependence of enhancement kinetics on the VPF/VEGF expression. The pathophysiologic basis for the differences in contrast enhancement patterns of tumors detectable by MRI is mainly due to vascular permeability, which leads to more characteristic differences than vascular density. MRI is able to subclassify malignant breast tumors due to their different angiogenetic properties.

Adult↗
PubMed1999

Trypsinogen activation peptides (TAP) in peritoneal fluid as predictors of late histopathologic injury in necrotizing pancreatitis of the rat.

The levels of trypsinogen activation peptides (TAP) were quantified by ELISA immunoassay in acute pancreatitis of the rat and compared to the degree of late histopathological sequelae and exocrine functional impairment 4 and 12 weeks after the acute phase of the disease. For this purpose acute pancreatitis of different severity was induced using a suitable rat model recently described. Forty five surviving animals were studied. The level of TAP in peritoneal exudate measured 3 and 6 hr after pancreatitis induction correlated well with the amount of the late histopathological injury at the end of the corresponding observation period (at 4 weeks after 3 hr: r = 0.75, P = 0.003, after 6 hr: r = 0.72, P = 0.005, Pearson; and at 12 weeks after 3 hr: r = 0.86, P = 0.0001, after 6 hr: r = 0.84, P = 0.0001, Pearson). A negative correlation of TAP with the impairment of exocrine function was found only at 4 weeks for the secretion of total protein (r = -0.76 after 3 hr; r = -0.62 after 6 hr) and for exocrine function (r = -0.67 after 3 hr, r = -0.57 after 6 hr), but not at 12 weeks after acute pancreatitis. No correlation with plasma amylase and lipase was found. We conclude that quantitation of TAP in ascites provides an accurate prediction of late histopathologic sequelae. Pancreatic exocrine function could be predicted by TAP assay only in the early stage after pancreatitis induction (eg, four weeks). In later stages of the disease (eg, 12 weeks) remaining pancreatic tissue seems to compensate for any exocrine deficits that have occurred.

Animals↗
PubMed1998

Extensive and predominant in situ component in breast carcinoma: their influence on treatment results after breast-conserving therapy.

Intramammary tumour recurrence is one of the most important problems in breast-conserving therapy. We reviewed a series of 957 patients treated with breast-conserving therapy for primary invasive breast carcinomas between 1 January 1985 and 31 December 1992 at the University of Heidelberg. All histological slides were re-evaluated for risk factors with special emphasis on the extent and subclassification of the in situ tumour and the margin status. Six parameters were identified as significant risk factors for intramammary recurrence in the univariate analysis, including extensive or predominant in situ component (EIC, with at least twice the greatest dimension of the invasive tumour component), histological grade, angioinvasion, lobular tumour type, involved resection margin and lymph node status. The presence of an EIC was statistically correlated with low tumour grade, tumour at the resection margins and in re-excision specimens and with multifocal tumour invasion. Multivariate logistic regression analysis revealed that EIC (relative risk (RR) = 1.9), tumour grade (RR = 1.76), angioinvasion (RR = 1.34), lobular tumour type (RR = 1.65) and young age (< or = 40 years, RR = 1.39) were independent predictors of local recurrence. When combining these factors in a linear model, the simultaneous presence of at least two of the five risk factors predicted a 5-year risk of intramammary recurrence of 20.9% compared with a risk of only 1-5% when none or one of these risk factors were identifiable. We conclude that the risk of subsequent intramammary recurrence after breast-conserving therapy can be estimated from a scoring system that includes four histological risk factors and the patient's age.

Adenocarcinoma, Mucinous↗
PubMed1998

Aberrant cytoplasmic expression of the p16 protein in breast cancer is associated with accelerated tumour proliferation.

The p16 protein plays an important role in the transition of cells into the G1 phase of the cell cycle. We have studied the prevalence of p16 protein expression in breast carcinomas in a prospective series of 368 invasive and 52 non-invasive malignancies, as well as in 88 locally recurring tumours and three tumour cell lines. p16 protein expression was evaluated immunohistochemically on paraffin sections using monoclonal and polyclonal anti-p16 antibodies, and by immunoblotting of tumour cell suspensions. Tumour cell lines were also subjected to polymerase chain reaction-single strand polymorphism (PCR-SSCP) analysis and direct DNA sequencing. The results were compared with established prognostic parameters, DNA flow cytometry and p53 protein expression. In 33 (9%) invasive and two (4%) intraductal carcinomas, a cytoplasmic accumulation of the p16 protein was seen. These cases were characterized by poor histological grade of differentiation, loss of of oestrogen receptors and progesterone receptors and frequent overexpression of the p53 protein. In addition, breast carcinomas with aberrant p16 expression demonstrated a high proliferative activity, with median S-phase fractions 74% higher than in the control group and the median Ki67 fractions elevated to 75%. A genetic alteration of the p16 gene was not detectable in three analysed cell lines with cytoplasmic p16 expression applying PCR-SSCP and direct DNA sequencing. These results indicate that cytoplasmic accumulation of the p16 protein identifies a subset of highly malignant breast carcinomas with accelerated tumour proliferation and other unfavourable parameters in breast cancer. The described protein accumulation is apparently not caused by an alteration of the p16 gene.

Blotting, Western↗
PubMed1998

[Complete remission after salvage chemotherapy in metastatic breast carcinoma after failure of induction cycles of planned high dosage chemotherapy with stem cell support].

We report on a patient with metastatic breast cancer confined to visceral (lung and pleura) site. A high-dose chemotherapy with peripheral progenitor blood cell transplantation was indicated. In contrast to other 24 patients two induction cycle chemotherapies (intensive dosis of Epirubicin/Ifosfamid/GCSF) didn't show any remission of metastases. Therefore a high dose chemotherapy with peripheral progenitor blood cell transplantation was not indicated any more. This patient had lung and pleura metastases and showed a complete remission after the following conventional chemotherapy (Carboplatin/Toxol) persisting more than 7 months. Non-responder after induction therapies have a poor prognosis but salvage therapy may be successful anyway. Mammary neoplasms can be sensible on special chemotherapy drugs only.

Adult↗
PubMed1997

[DNA cytometry in breast carcinoma. Review of method and value in assessing prognosis].

DNA flow cytometry (FCM) has become a routine method in breast cancer diagnosis for evaluation of ploidy and proliferation kinetics (cell cycle analysis). Image cytometry is less practicable and provides less information than flow cytometry. An optimized technique with a low coefficient of variation is required for optimal results in flow cytometry. The S-phase fraction and the proliferation index (sum of S-phase fraction and G2M fraction) provide prognostic and therapeutically relevant information. A profound knowledge of the technique and its limitations is indispensable for the interpretation of FCM results. It remains to be established whether immunohistological evaluation of cell proliferation has the same prognostic value. Future developments are to be expected from multiparametric analysis and the improvement of mathematical analysis of FCM measurements.

Breast↗
PubMed1997

[Subtyping and prognostic assessment of invasive lobular breast carcinoma].

Invasive lobular carcinoma (ILC) is recognized in its classical form and as variants with tubulo-lobular, solid, pleomorphic, alveolar or signet ring cell differentiation. The most common classical form differs from invasive ductal carcinoma (IDC) by its slower tumor proliferation and less common axillary metastases. When compared stage by stage, long term prognosis is similar to IDC, however. Prognostic subtyping of ILC can be achieved by the recognition of variant forms and mitotic counting. The combination of these factors may be used for tumor grading (5-year survival 100% with grade 1 vs. 82% with grade 2, and 57% with grade 3, n = 241). The detailed histopathologic diagnosis therefore permits prognostic assessment also in ILC.

Adult↗
PubMed1996

Benefits of various dextrans after delayed therapy in necrotizing pancreatitis of the rat.

OBJECTIVE: Ultrahigh-molecular dextran (500,000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline? ANIMALS AND INTERVENTIONS: Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n = 10 per group) receiving either Ringer solution or different dextrans (10%) including 70,000 Da (DEX-70), 160,000 Da (DEX-160), 300,000 Da (DEX-300) or 500,000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg. MEASUREMENTS AND RESULTS: Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significantly lower in DEX-70 and DEX-160 compared to Ringer controls (p < 0.05, t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p < 0.01, t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p < 0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70. CONCLUSIONS: Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects.

Animals↗
PubMed1995

CD44 variant exon epitopes in primary breast cancer and length of survival.

CD44 designates a group of closely related cell-surface proteins generated by alternative splicing. We have previously shown that splice variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines and that they confer metastatic behaviour on non-metastatic animal tumour cell lines. In this study we set out to assess the expression of CD44 epitopes specific for variant exon sequences in human breast cancer and their potential for determining prognosis. We used affinity-purified polyclonal sera and four monoclonal antibodies raised against the human homologues of CD44 variant exon sequences to investigate the presence of CD44 on 100 primary invasive breast tumours, 12 local recurrences, 18 lymph node metastases, and normal tissue controls. Whereas normal mammary ductal epithelial cells and cells derived from hyperplastic lesions do not express CD44 variant exons, expression of v3, v5, and v6 epitopes was found in most tumour samples. The DIII (exon v6) epitope was present in 84% of the primary tumours and in 100% of axillary lymph node metastases and local recurrences. The presence of these CD44 epitopes is correlated with poor overall survival. 15 patients with exon-v6-negative tumours had good survival compared with 76 patients with exon-v6-positive tumours (p = 0.005; log rank test). Multivariate analysis showed that the CD44 epitope encoded by exon v6 was a good marker for prognosis independent of progesterone receptor, lymph node status, tumour size, and grade.

Adult↗
PubMed1995

Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression, a new prognostic factor in human breast cancer.

In different human tumors, splice variants of the surface glycoprotein CD44 (CD44v) are correlated with advanced stages of tumor growth and metastatic potential. In breast cancer and colon cancer, expression of epitopes encoded by exon v6 on primary tumors is an independent prognostic factor for poor patient survival. Two different screening methods for the detection of CD44 variants in tumors have been applied: immunohistochemistry (IHC) and semi-quantitative reverse transcription PCR (RT-PCR). In this study, we have compared the predictive capacity and the applicability of both approaches, using 31 human breast-tissue specimens (normal and neoplastic). IHC reveals lack of expression of CD44v on normal ductal epithelial cells but strong expression on myoepithelial cells. The majority of tumors express CD44 epitopes encoded by several variant exons. RT-PCR detects splice variants in normal epithelium, probably derived from RNA expressed in the myoepithelium. In tumors, RT-PCR reveals expression of a wide range of splice variants, including new ones that are not detected in normal breast tissue, e.g. ones that contain all variant exons. The conclusion of this comparison is that IHC is the better method for breast-tumor sample screening but that the increased sensitivity of RT-PCR can help to distinguish CD44v-positive from CD44v-negative tumors in cases where only a few tumor cells express variants or where epitopes are masked.

Antigens, Neoplasm↗
PubMed1995

Effects of passive immunization against parathyroid hormone-related protein: PTHrP is the responsible factor in mediating hypercalcemia in the Walker carcinosarcoma 256 rat model.

The Walker carcinosarcoma (WCS) 256 is a well-characterized rat model of humoral hypercalcemia of malignancy (HHM). We addressed the question of whether parathyroid hormone-related protein (PTHrP) is the factor responsible for mediating HHM in this model. WCS 256 cells were subcutaneously implanted in female rats. We examined the plasma at days 0, 2, 4, 6, and 8. The midregional PTHrP measured by radioimmunoassay (RIA) and the plasma calcium increased significantly. Measuring PTHrP by a two-site immunoradiometric assay (IRMA) showed comparable results. There was a strong positive correlation between plasma calcium and midregional PTHrP (r = 0.85, p < 0.0001). A strong positive correlation between tumor weight and both midregional PTHrP (r = 0.83, p < 0.0001) and plasma calcium (r = 0.87, p < 0.0001) was also found. After surgical removal of the tumor at day 5, both plasma calcium and plasma PTHrP levels fell to within the normal range. Ip administration of native polyclonal antiserum against PTHrP(53-84) led to a significant decrease of plasma calcium. Extracted WCS 256 tumor showed 5-fold increased levels of midregional PTHrP compared with liver. Immunohistochemistry and Western blot were positive for PTHrP. RNA from the WCS 256 tumor was positive for PTHrP whereas liver tissue RNA was negative. WCS 256 cells grown in vitro also secreted PTHrP into the medium. We conclude that PTHrP is synthesized and secreted by WCS 256 and that PTHrP is the factor responsible for mediating hypercalcemia in the WCS 256 rat model.

Analysis of Variance↗
PubMed1995

Human mammary carcinomas express homologues of rat metastasis-associated variants of CD44.

Splice variants of CD44 expressed in a metastasizing cell line derived from a rat pancreatic adenocarcinoma have been shown recently to confer metastatic potential onto non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Homologues of these variants have also been detected in a variety of human malignancies. Using antibodies raised against a bacterially expressed fusion protein containing variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins on tumors of the female breast. The material examined included normal tissue, hyperplastic lesions, 103 primary invasive mammary carcinomas, 10 in situ carcinomas, 12 local recurrences and 18 lymph node metastases. Using a polyclonal serum directed against several variant CD44 epitopes, normal mammary epithelia as well as ductal hyperplasias were negative for these splice variants, while the variant CD44 epitopes were detectable in all but six of the primary invasive carcinomas. From the reaction with various monoclonal antibodies and polyclonal sera specific for individual epitopes it is obvious that the tumors predominantly express CD44 variants encoded by exons v5 to v7. Interestingly, all investigated lymph node metastases reacted positively with the variant-specific antibodies, in contrast to primary tumors which reacted in 54% to 86% of the cases, depending on the antibody used. Statistical analysis revealed a significant correlation between expression of variant exons v3/v4 and v6 and increased tumor grade (p = 0.001 and p < 0.05, respectively; Fisher's exact test). Exon v6 is carried by the variants which confer metastatic capability in the rat. These results indicate that the expression of the CD44 variants is upregulated in mammary carcinomas and is closely linked to tumor anaplasia.

Animals↗
PubMed1995

Hyperoncotic dextran and systemic aprotinin in necrotizing rodent pancreatitis.

BACKGROUND: Dextrans improve pancreatic microcirculation in acute experimental pancreatitis. They could therefore facilitate the transport of a protease inhibitor to ischemic areas of tissue injury and be of additional benefit. METHODS: To compare the effects of dextrans with and without aprotinin, necrotizing pancreatitis was induced in 33 male dextran-resistant Wistar rats by intraductal infusion of low-dose glycodeoxycholic acid (10 mmol/l) followed by intravenous cerulein (5 micrograms/kg/h) for 6 h. Three and four hours after the start of the cerulein infusion the animals received infusions of either Ringer's lactate (RL) (12 ml/kg), 70,000 Da dextran (10%) (DEX-70) (4 ml/kg) alone, or DEX-70 (4 ml/kg) with aprotinin (5000 IU/kg) (DEX-70/A). RESULTS: The death rate was 60% within 9 h in the RL group (6 of 10) but only 10% in the DEX-70 group (1 of 10) (p < 0.03; Fisher's exact test) and 23% in the DEX-70/A group (3 of 13). Histomorphometry demonstrated a significant reduction of acinar necrosis in both treatment groups compared with control animals (p < 0.014; t test). Total amounts of trypsinogen activation peptides (TAP) in ascites were also significantly lower in these groups (p < 0.05; t test). CONCLUSIONS: DEX-70 given 3 h and 4 h after induction of pancreatitis significantly reduced the levels of TAP, limited acinar necrosis, and improved survival rate in acute necrotizing rodent pancreatitis. There was no additional benefit from the combination with aprotinin.

Acute Disease↗
PubMed1994

Metastatic potential of small and minimally invasive breast carcinomas.

Invasive ductal mammary carcinomas (IDC) of 1 cm in tumour size or less account for less than 20% of all IDC. We have observed 167 such cases at our Institution between 1985 and 1989. These were divided into carcinomas with an extensive or predominant intraductal component (EIC or PIC, being least 2x or 4x larger than the invasive component; 90) and compared statistically with the control group (no EIC or PIC; 77) for known prognostic factors and for their metastatic behaviour. Lymph nodes were step sectioned in order to detect occult micrometastases. The median follow up time was 62.6 months. Lymph node metastases were seen in 10% of pT1a and 19% of pT1b cases. Significant differences were found when comparing the EIC/PIC group with the control group (pT1a: 11% vs. 0%, pT1b: 37% vs. 11% lymph node metastases). Also, axillary and infraclavicular recurrence rates were higher for EIC/PIC carcinomas compared with other IDC of < or = 1 cm (9.3% vs. 4.2%). This significantly adverse metastatic behaviour of the EIC/PIC tumours may be in part due to the more frequent occurrence of multifocal tumours in this group (in 43% vs. 6%), resulting in a greater tumour burden. We conclude that the overall risk of lymph node metastasis is not negligible in carcinomas of 1 cm or less in diameter with the risk being more than doubled for carcinomas with an intraductal component exceeding the invasive tumour by a factor of two. These differences were relevant only to regional metastases; the risk for distant metastasis and survival was identical after 5 years.

Breast Neoplasms↗