Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice.

We have studied the expression of members of the bcl-2 family in human breast cancer. The expression pattern of these genes in breast cancer tissue samples was compared with the expression pattern in normal breast epithelium. No marked difference with regard to bcl-2 and bcl-xL expression was observed between normal breast epithelium and cancer tissue. In contrast, bax-alpha, a splice variant of bax, which promotes apoptosis, is expressed in high amounts in normal breast epithelium, whereas only weak or no expression could be detected in 39 out of 40 cancer tissue samples examined so far. Of interest, downregulation of bax-alpha was found in different histological subtypes. Furthermore, we transfected bax-alpha into breast cancer cell lines under the control of a tetracycline-dependent expression system. We were able to demonstrate for the first time that induction of bax expression in breast cancer cell lines restores sensitivity towards both serum starvation and APO-I/Fas-triggered apoptosis and significantly reduces tumor growth in SCID mice. Therefore, we propose that dysregulation of apoptosis might contribute to the pathogenesis of breast cancer at least in part due to an imbalance between members of the bcl-2 gene family.

Cytoplasmic overexpression of ALCAM is prognostic of disease progression in breast cancer.

BACKGROUND: Activated leucocyte cell adhesion molecule (ALCAM, CD166) is a cell surface member of the immunoglobulin superfamily. ALCAM expression has prognostic relevance in prostate and colon cancer. OBJECTIVE: To evaluate ALCAM protein expression in breast cancer by immunohistochemistry and to correlate expression levels with clinicopathological data. METHODS: 162 primary breast carcinomas with a mean clinical follow up time of 53 months were immunostained using a monoclonal ALCAM antibody. The staining was evaluated as an immunoreactive score (IRS) and grouped into low v high for both membranous and cytoplasmic staining. RESULTS: Intraductal and invasive carcinomas showed a higher ALCAM expression (median IRS 4 and 6 respectively) than normal breast tissue (IRS 2). In univariate survival analyses a significant association of high cytoplasmic ALCAM expression with shortened patient disease-free survival (mean (SD) five year non-progression rate, 69.4 (4.6)% v 49.4 (11.1)%, p = 0.0142) was found. In multivariate analyses of disease-free survival times, high cytoplasmic ALCAM expression (relative risk (RR) = 2.086, p = 0.026) and nodal status (RR = 2.246, p = 0.035) were significantly associated with earlier disease progression, whereas tumour grading (RR = 1.6, p = 0.052) was of borderline significance. CONCLUSIONS: The data suggest that strong cytoplasmic ALCAM expression in primary breast cancer, as detected by immunohistochemistry, might be a new marker for a more aggressive breast cancer biology.

A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor gene for breast cancer.

Recent evidence obtained by cytogenetic and molecular studies indicates that in breast cancer chromosome 6q is often affected by genetic changes suggesting the existence of putative tumor suppressor genes (TSGs). However the function of gene(s) on this chromosome in breast cancer suppression is not understood. To substantiate further the presence of breast cancer related TSGs at 6q and to define their location, we first performed microcell-mediated transfer of chromosome 6 to CAL51 breast cancer cells for studying possible suppression of malignant phenotype and secondly, we analysed DNAs from 46 primary breast cancers for loss of constitutive heterozygosity (LOH) using 24 poly-morphic microsatellite markers. The chromosome transfer resulted in loss of tumorigenicity and reversion of other neoplastic properties of the microcell hybrids. Polymorphism analysis of single hybrids revealed that they harbored only a small donor chromosome fragment defined by the marker D6S310 (6q23.3-q25) and flanked by D6S292 and D6S311. The LOH data suggest that four tumor suppressor gene loci mapped to the central and distal portion of 6q may be independently deleted in breast cancer. One of these regions corresponds to the region identified by chromosome transfer.

The impact of laparoscopic biopsy of pancreatic lymph nodes with helium and carbon dioxide on port site and liver metastasis in BOP-induced pancreatic cancer in hamster.

The influence of pancreatic biopsy during laparoscopy with carbon dioxide (CO2) and helium on the incidence of port site and liver metastasis in pancreatic carcinoma is still unknown. Ductal adenocarcinoma of the pancreas was induced in Syrian hamsters (n = 30) by injection of N-nitrosobis-2-oxopropylamin (BOP, 10 mg/kg body weight/week) for 12 weeks. In week 13, hamsters were randomized in 3 groups (n = 10): While in group 1 (gr. 1) a laparotomy and biopsy of pancreatic lymph nodes was performed, gr. 2 and gr. 3 underwent a laparoscopic biopsy either with CO2 or helium. Therefore, one trocar was located in the left (biopsy) and the right abdominal wall (camera). In the 18th week all animals were sacrificed and the incidence of abdominal wall, port site and liver metastases was histologically determined. While there were abdominal wall metastases after laparotomy in 10% (n = 1), we observed trocar metastases in the CO2 group in 20% (n = 2). However, there were no trocar metastases in the helium group. The incidence of liver metastasis did not differ between the laparotomy and the helium group (20% vs 30%), but was increased in the CO2 group (60%). Laparoscopic biopsy of pancreatic lymph nodes with CO2 increased the incidence of port site and liver metastases in pancreatic cancer. The helium group was equal to the laparotomy group in this respect. Thus, staging laparoscopy with helium might become an alternative to explorative laparotomy in pancreatic cancer.

Effects of taurolidine and octreotide on port site and liver metastasis after laparoscopy in an animal model of pancreatic cancer.

Port site metastasis is a dreadful event following laparoscopy; however, the exact pathomechanism is still unknown. In order to prevent trocar metastasis we determined the effects of intraperitoneal lavage with either taurolidine or octreotide on port site and liver metastasis after laparoscopy in a chemically induced, solid pancreatic adenocarcinoma. Pancreatic adenocarcinoma was induced in 60 Syrian hamsters by weekly injection of 10 mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. Six weeks later, a laparoscopic pancreatic biopsy was performed by the use of a pneumoperitoneum with carbon dioxide (12 mm Hg), followed by an abdominal irrigation with 5 ml normal saline (group 1, n = 20), 5 ml 0.5% taurolidine (group 2, n = 20) or 5 ml octreotide (20 mg/ml) (group 3, n = 20). After 8 weeks, all hamsters were sacrificed and histopathologically examined. There was only one macroscopic visible primary tumor in the taurolidine group (5.9%), compared to 42.1% in the saline group and 62.5% in the octreotide group (P < 0.05). The size of carcinomas was smaller in the saline group than after octreotide irrigation (median 6, range 2-25 vs. median 70, range 40-160 mm2, P < 0.05). The number of liver metastases per animal was increased after saline irrigation (median 4, range 2-6), compared to taurolidine (median 2, range 1-3) or octreotide (median 2.5, range 2-4) (P < 0.05). Port site metastases were found in 36.8% after saline, in 37.5% after octreotide and in 0% after taurolidine irrigation (P < 0.05). Thus port site metastasis was effectively prevented by taurolidine irrigation after staging-laparoscopy in pancreatic cancer.

Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters.

Selective inhibition of eicosanoid synthesis is thought to have effects on carcinogenesis in lung and colon cancer. However, it is still unknown whether pancreatic cancer might also be influenced. Therefore we evaluated the impact of selective cyclooxygenase-2 inhibitor Celebrex and selective 5-lipoxygenase inhibitor Zyflo on liver metastasis in a solid model of pancreatic adenocarcinoma in Syrian hamster. In week 33, the animals were sacrificed and incidence of pancreatic carcinomas and number and size of liver metastases were determined. Activities of antioxidative enzymes (GSHPX/SOD) and concentrations of products of lipidperoxidation were measured in liver metastases and non-metastatic hepatic tissue. The incidence (54.5 vs. 100%), number (3.17 +/- 0.98 vs. 6.75 +/- 0.71) and size (2.67 +/- 1.97 vs. 11.75 +/- 1.98 mm2) of liver metastases were decreased by combined therapy of Zyflo and Celebrex (P < 0.05). Furthermore, activities of GSHPX ([73.77 +/- 5.67]*10(5) vs. [15.49 +/- 4.02]*10(5) U/mg prot.; P < 0.05) and SOD (474.92 +/- 108.8 vs. 127.89 +/- 38.75 U/mg prot.; P < 0.05) were increased, while lipidperoxidation (0.31 +/- 0.08 nmol/mg prot. vs. 1.54 +/- 0.55 nmol/mg prot.; P < 0.05) was decreased by combination therapy, in non-metastatic hepatic tissue. Moreover, combined therapy increased lipidperoxidation in liver metastases (0.47 +/- 0.09 vs. 1.95 +/- 0.12 nmol/mg prot.; P < 0.05). Thus, a combination of Celebrex and Zyflo might be a new concept to decrease tumour growth in liver metastases in advanced pancreatic cancer.

Radiation therapy after breast-conserving surgery; first results of a randomised clinical trial in patients with low risk of recurrence.

To study the role of radiotherapy and tamoxifen after breast-conserving surgery (BCS) in patients with a favourable prognosis, a clinical trial was initiated by the German Breast Cancer Study Group. Between 1991 and 1998, 361 patients (pT1pN0M0, aged 45-75 years, receptor positive, grade I-II) were randomised to radiotherapy (yes/no) and tamoxifen for 2 years (yes/no) in a 2x2 factorial design; the exclusion of seven centres (14 patients) left 347 patients in the analysis. After a median follow-up of 5.9 years, 77 events concerning event-free survival have been observed. Since a strong interactive effect between radiotherapy and tamoxifen has been established, the results are presented in terms of the treatment effects for all four treatment groups separately. Mainly due to the presence of local recurrences, the event rate was about three times higher in the group with BCS only than in the other three groups. No difference could be established between the four treatment groups for distant disease-free survival rates. It is concluded that even in patients with a favourable prognosis, the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially.

Does alpha-linolenic acid in combination with linoleic acid influence liver metastasis and hepatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters?

Some fatty acids are reported to inhibit tumor growth of pancreatic carcinoma. However, it is still unknown if alpha-linolenic acid (ALA) and linoleic acid (LA) inhibit liver metastasis of ductal pancreatic adenocarcinoma. Therefore we studied the effect of these fatty acids on liver metastasis in the animal model of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic adenocarcinoma in Syrian hamsters. Since lipid peroxidation seems to be involved in carcinogenesis and metastasis, we further analyzed the intrahepatic concentration of thiobarbituric acid-reactive substances (TBARS) and activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). We observed an increase in the incidence and the number of liver metastases in response to the combination of ALA and LA. This was accompanied by a decrease in hepatic GSH-Px activity and an increase in hepatic SOD activity and TBARS concentration. The increase in hepatic lipid peroxidation seems to be one possible mechanism of increasing liver metastasis in this study.

Effects of taurolidine and octreotide on tumor growth and lipid peroxidation after staging-laparoscopy in ductal pancreatic cancer.

Irrigation with taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n = 20) with subsequent laparoscopic irrigation with taurolidine (gr. 2, n = 20) or octreotide (gr. 3, n = 20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group (P<0.05). Carcinomas were smaller after saline (6+/-23 mm(2)) than after octreotide irrigation (70+/-120 mm(2), P<0.05). In conclusion this study showed that laparoscopic irrigation with taurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.

Influence of conjugated and conventional linoleic acid on tumor growth and lipid peroxidation in pancreatic adenocarcinoma in hamster.

Conventional linoleic acid (LA) is regarded as a promotor of carcinogenesis. However, the effect of its conjugated derivative on cancer is still unknown. Therefore we investigated the influence of conventional and conjugated LA on tumor growth and lipid peroxidation in a solid model of pancreatic adenocarcinoma in Syrian hamsters. 60 male hamsters were randomized in 4 groups (Gr.) (n=15). Gr. 1 and 2 received 0.5 ml 0.9% sodium chloride subcutaneously (s.c.) once a week while Gr. 3 and 4 were injected 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly for 12 weeks to induce pancreatic cancer. Gr. 1 and 3 received a diet containing conventional LA, Gr. 2 and 4 were fed a diet of conjugated LA. After 29 weeks all animals were sacrificed, pancreas was weighed and examined macroscopically and histologically. The level of lipid peroxidation and activities of glutathion peroxidase and superoxide dismutase were determined in tumor-free as well as in pancreatic carcinoma tissue. Different diets did not influence the incidence of pancreatic carcinoma, however, pancreas weight was increased by conjugated LA compared to conventional LA. Furthermore both diets decreased the activity of glutathion peroxidase and increased the level of lipid peroxidation in pancreatic intratumoral tissue. The content of conjugated LA in dietary did not influence pancreatic tumor growth in a solid model of pancreatic adenocarcinoma in Syrian hamsters.

Influence of conjugated vs. conventional linoleic acid on liver metastasis and hepatic lipidperoxidation in BOP-induced pancreatic cancer in Syrian hamster.

While conjugated linoleic acid (CLA) is regarded as an essential fatty acid with anticarcinogenic effects, conventional linoleic acid (LA) is reported to promote tumour growth in various experimental studies probably caused by high sensitivity to non-enzymatic lipid peroxidation. In order to evaluate the impact of dietary LA and CLA on liver metastasis and lipidperoxidation (LPO), 60 Syrian hamsters were injected with 10 mg N -nitrosobis-2-oxopropylamine (BOP)/kg body weight s.c. for 12 weeks. Animals were fed a special diet containing LA or CLA. The experiment was terminated after 24 weeks. Incidence, number and size of liver metastases were histologically determined. Furthermore, the activities of antioxidative enzymes and concentration of hepatic lipidperoxidation were measured intra- and extrametastatically. Incidence, number and size of liver metastases did not differ between the tumour groups. Otherwise, antioxidative enzyme activity of GSH-Px was higher in non-metastatic liver, while SOD activity and lipidperoxidation were increased in liver metastases. Conclusively there was no difference between the groups fed with LA and CLA according to the impact on liver metastasis in ductal pancreatic cancer.

Influence of antioxidative vitamins A, C and E on lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

Persistent oxidative stress is thought to play an important role in carcinogenesis. Vitamins may influence oxygen radical metabolism and thus inhibit tumor growth. In the present trial the effects of Vitamins (Vit.) A, C and E on neoplastic growth and lipid peroxidation in pancreatic tissue were evaluated on chemically-induced pancreatic adenocarcinoma in the Syrian hamster. The incidence of pancreatic cancer was decreased by Vit. A (64.3%) and Vit. C (71.4%) as compared to the control group (100%, P<0.05). All vitamins increased the activity of superoxidedismutase (SOD) in pancreatic carcinomas. Accumulation of vitamins in tumor cells seems to be responsible for high levels of SOD and consecutive intracellular increase of hydrogen peroxide levels. Since this effect is selectively toxic for tumor cells it might be one of the mechanisms decreasing the incidence of pancreatic cancer in our trial.

Influence of octreotide on liver metastasis and hepatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

INTRODUCTION: In prospective clinical trials, octreotide improved quality of life and survival time in patients with pancreatic cancer. AIMS: To analyze whether octreotide modulates the hepatic oxygen radical metabolism and thus might decrease liver metastasis in an animal model of pancreatic cancer. METHODOLOGY: Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine (BOP) for 3 months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters received a standard diet (3.5% fat) or were fed a high-fat diet (21.4% fat). In the 25th week, the pancreas and liver were examined macroscopically and histologically. The level of lipid peroxidation and activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined intrahepatically. RESULTS: The number of liver metastases per animal and the size of liver metastases were increased by the high-fat diet, whereas they were decreased by octreotide. Octreotide increased activities of GSH-Px and SOD. The concentration of thiobarbituric acid reactive substances was increased by BOP and a high-fat diet and decreased by octreotide. CONCLUSION: Octreotide decreases the number and size of liver metastases in chemically induced pancreatic cancer in Syrian hamsters. This is accompanied by high hepatic GSH-Px and SOD activity and a low level of lipid peroxidation.

Validation of a new experimental model of colon cancer.

BACKGROUND: Most of the published animal studies that have evaluated tumor growth and port site metastases in laparoscopy have utilized a cell suspension model and thus cannot be compared to the clinical situation. Although solid tumor models have been developed, there has been no experimental model that establishes an orthotopic tumor in the rectum, reflecting the clinical situation of a solid colonic cancer. METHODS: Tumor cells (colon adenocarcinoma DHD/K1/TRb) were administered intraperitoneally in rats, which were used as solid tumor donors. A 20-mg piece of solid tumor from the donor was placed in a submucosal blister created in the rectum wall of the study rats. The approach to the submucosal blister was made through the mucosa after contralateral enterotomy. In order to validate the model, this intervention was performed in 10 cases (group A). After 10 days of intervention, the rats were submitted to resection of the rectum and histological examination of the specimen. In another 10 rats (group B), manipulation of the tumor was performed after 10 days to cause tumor cell spillage. The likelihood of tumor dissemination was investigated in this group 20 days after this intervention. RESULTS: Group A developed solid tumors in seven of 10 cases (70%). All of the tumors were localized between the muscular and the mucosal layer, with preservation of the serosa and without affecting the enterotomy. In all of the rats in group B, macroscopic tumor was observed in the upper rectum (100%) 10 days after its induction. Twenty days after tumor manipulation, nine rats had local tumor dissemination; two of them also had general tumor dissemination in the abdominal cavity. CONCLUSIONS: We established a novel solid colonic tumor model in rats for the investigation of intraoperative tumor cell spillage during resection of the colon and the development of port site metastases.

The impact of laparoscopic biopsy of pancreatic lymph nodes on lipid peroxidation using helium and carbon dioxide in BOP-induced pancreatic cancer in hamsters.

BACKGROUND: Increased lipid peroxidation is believed to stimulate liver metastasis in pancreatic cancer. However, the effect of the laparoscopic biopsy of pancreatic lymph nodes on liver metastasis is still unknown. We hypothesized that the effects of a pneumoperitoneum with carbon dioxide (CO2) increase lipid peroxidation and stimulate liver metastasis. METHODS: Ductal pancreatic adenocarcinoma was induced in Syrian hamsters (n = 30) by weekly subcutaneous injections of N-nitrosobis-2-oxopropylamine (BOP) for 12 weeks. In group 1, a laparotomy and biopsy of pancreatic lymph nodes was performed. Groups 2 and 3 underwent laparoscopic biopsy with either CO2 or helium. In the 5th postoperative week, the hamsters were killed and the incidence of liver metastasis was analyzed histopathologically. We then made determinations of the level of lipid peroxidation (thiobarbituric acid-reactive substances [TBARS])as well as the activity of glutathionperoxidase (GSH-PX) and superoxidismutase (SOD) in pancreatic carcinoma and liver metastases of the animals. RESULTS: The incidence of liver metastasis was higher in the CO2 group (60%) than in the helium (30%) and laparotomy groups (20%) (p < 0.05). The concentration of TBARS was greater in pancreatic carcinoma and intrametastatic hepatic tissue than in extratumorous pancreatic and extrametastastic hepatic tissue in all groups. Extrametastatic hepatic concentration of TBARS was higher in the CO2 group (19.4 +/- 0.88 nmol/mg protein) than the laparotomy (10.66 +/- 0.95 nmol/mg protein) and helium groups (10.79 +/- 0.58 nmol/mg protein). GSH-PX and SOD activity was significantly lower in pancreatic carcinoma tissue and intrametastatic hepatic tissue than in extratumorous pancreatic and extrametastatic hepatic tissue. However, in the CO2 group (1.24 +/- 0.48 107 U/mg protein), extrametastatic GSH-PX activity was lower than in the laparotomy (1.73 +/- 0.4 107 U/mg protein) and helium groups (1.63 +/- 0.28 107 U/mg protein). CONCLUSION: After laparoscopic biopsy of pancreatic lymph nodes in the CO2 group, lipid peroxidation was increased and GSH-PX activity was decreased in extrametastatic hepatic tissue compared to the intrametastatic sections. This mechanism may be responsible for the increased liver metastasis in the CO2 group.

Determination of the structure of tissue samples using X-ray small angle scattering.

X-ray small angle scattering has been used in material science for about 50 years. In diagnostic medicine, it has been applied for some years. The theoretical background is the diffraction of monochromatic X-rays by the electrons of small particles. The widening of the primary beam by those samples allows a conclusion regarding particle size, size distribution, and the form of the particles. The camera requires a well-defined and small X-ray beam which has to be entrapped exactly behind the sample. To date, the medical application has been carried out mainly by the comparison of the measured curve with that of standard samples. It can be suggested that in the near future its application in medicine will increase particularly with regard to in vivo measurements. For this purpose, new cameras will have to be developed. An exact evaluation of the result requires a thorough knowledge of the theoretical basis.

[Automated mammary sonography and mammography: the differentiation of benign and malignant breast lesions]. / Automatisierte Mammasonographie und Mammographie: Differenzierung benigner und maligner Mammaläsionen.

PURPOSE: A prospective study on the differentiation of breast lesions was carried out using experimental combination schemes of mammography and automatic sonography. MATERIALS AND METHODS: X-ray mammograms and a B image from automatic sonography of 39 malignant and 41 benign lesions as well as 40 cases without lesions were separately examined by four experienced diagnosticians. The observers differentiated the findings mammographically and by measurement in the B images. RESULTS: For two examiners the combination of mammography and automatic sonography gave with regard to the differentiation of breast lesions an improvement in sensitivity of 3 or 5% and in specificity of 31 and 18%, respectively, as compared to mammography alone while for the other two examiners an improved specificity of 21 and 36%, respectively, was accompanied by an 8 and 10% decrease in sensitivity as compared to mammography alone. CONCLUSIONS: The differentiating criteria from automatic sonography and mammography can, in principle, be used to evaluate the dignity of breast lesions. However, an optimization is necessary since the improvement in specificity does not compensate the loss in sensitivity.

Increased incidence of cervical intraepithelial neoplasia in young women in the Mitte district, Berlin, Germany.

OBJECTIVE: To investigate whether the incidence of cervical intraepithelial neoplasia (CIN), in particular of high grade CIN, increased in Berlin during the period 1970-1989 and whether the ages of women with CIN had decreased. STUDY DESIGN: In the former German Democratic Republic, which had a highly centralized public health system, all gynecologic operations performed on women living in the Mitte district of Berlin were carried out during the period 1970-1989 (when the Berlin Wall fell) in the gynecologic clinic of the Charité Hospital. RESULTS: The incidence of all CIN increased from year to year over the observation period: 0.04% (1970-1971), 0.10% (1980-1981), 0.39% (1988-1989). There was a particularly high increase in the incidence of high grade intraepithelial neoplasms (CIN 3): 0.016% (1970-1971), 0.056% (1980-1981), 0.25% (1988-1989). With a virtually unchanged age distribution for women in the Mitte district of Berlin, the median age of women with CIN 3 decreased significantly from 1970 to 1989, from 39.5 (1970) to 33 (1989) (P < .001). CONCLUSION: The increase in the incidence of CIN, especially of high grade CIN, as well as the reduction in age for onset of the disease, makes high participation in screening necessary, above all among young women.

[Three-dimensional breast biopsy and surgery]. / Dreidimensionale Mammabiopsie und Chirurgie.

For the histological verification of suspicious non-palpable small breast tumors, the three-dimensional breast biopsy applied as cylindrical extirpation using the ABBI system is the optimal solution at present. Because of the possibility of performing mammography during the operation, errors of localization can be corrected and incorrect incisions avoided. Taking the three radiomorphologically leading symptoms into consideration--suspicious microcalcification, focal shadow and structural irregularity--it can be stated that the digital mammography of the ABBI system is more sensitive than the conventional one for detecting microcalcification, but focal shadow and structural irregularity are detected less well by digital technique. These structures should be preoperatively marked by using sonography. After the complete removal of suspicious microcalcification checked by digital mammography during the operation, residual tumor might be found in a second excision when histologically invasive or intraductal tumor terminations reach the excision margin (R1 resection). Thirteen invasive and 8 intraductal carcinomas were found in 80 cases of cylindrical extirpation using the ABBI system. In 7 procedures carried out to exclude an in-breast recurrence, 3 intraductal carcinomas and 1 invasive carcinoma were observed. In 8 of 12 invasive carcinomas and in 1 of 5 intraductal carcinomas, breast-conserving therapy was indicated. Two cases of invasive carcinoma fulfilled the criteria applied (minimal tumor-free margin > 2 mm, no extensive intraductal component) to use the ABBI cylinder as lumpectomy without a second excision to follow.

Changes in arterial function in a mouse model of human familial hypercholesterolaemia.

AIM: Atherosclerosis is the most common cause of cardiovascular disease. The ApoB mouse is a model for human familial hypercholesterolaemia and has a lipoprotein profile similar to that of humans with atherosclerosis. Therefore, it is a suitable model to investigate the changes in vasoreactivity during atherogenesis. This study investigates contractile and dilatative properties of arteries in this model in relation to age. METHODS: Male ApoB mice and B6, wild-type (WT), mice were examined at age four or 18 months. Isometric measurements of 2-mm ring preparations of the aorta thoracica were performed using a wire myograph. Histological and biochemical methods served to determine atherosclerosis, lipid status and endothelial markers respectively. RESULTS: Morphometric analysis showed that all old ApoB mice had severe atherosclerosis in the aorta. Atherosclerotic alteration of the aorta of the ApoB mice coincided with a diminished vasodilatation to acetylcholine. The phenylephrine response was significantly attenuated already to the same degree in the non-atherosclerotic aorta of the young ApoB mice as in the atherosclerotic aorta of the older ApoB mice. Serum parameters showed a rise in total cholesterol and triglycerides in the ApoB strain compared to WT mice. Soluble intercellular adhesion molecule (sICAM)-1 and soluble vascular adhesion molecule (sVCAM)-1 were increased in old compared to young ApoB mice. CONCLUSION: The study shows that reduced acetylcholine-induced dilatation is related to the presence of atherosclerosis in old ApoB mice. Remarkably, the impaired vessel reactivity to phenylephrine already in young ApoB mice indicates early changes in vascular function in this model.