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A Hennipman

Publications and source records attributed to A Hennipman.

25 records · Page 2Linked to original sources
PubMed1989

Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue.

Tyrosine specific protein kinase activity was determined in 70 specimens of the human mammary gland. These included 28 cancers of the breast, 21 benign breast diseases, and 21 normal breast tissues. We measured tyrosine kinase activity in the cytosol fraction and in the membrane fraction of the homogenates. In addition cytosolic aldolase activity was measured. Tyrosine kinase activity was determined using poly(glutamic acid:tyrosine = 4:1) as an artificial substrate. Cancers of the breast exhibited considerable higher tyrosine kinase activities in both cytosol and membrane fractions, compared to benign breast tumors (P less than or equal to 0.001). Benign tumors demonstrated increased activities in cytosol in comparison to normal breast tissues (P less than 0.001). Furthermore, there appears to be a strong association of an enhanced expression of activity of tyrosine kinase in cytosol of primary carcinomas and early systemic relapse. In combination with aldolase activity a nearly complete discrimination is achieved between malignant specimens on one hand and benign and normal tissues on the other.

Adult↗
PubMed1988

Heterogeneity of glycolytic enzyme activity and isozyme composition of pyruvate kinase in breast cancer.

In 6 patients with breast cancer - of whom specimens of the primary tumor as well as one of its metastases were available for examination - we demonstrated intratumoral and intertumoral heterogeneity in expression of activity of the glycolytic enzymes hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase. Heterogeneity also existed in isozyme composition of pyruvate kinase. The transition of the tumors towards normal surrounding breast tissue showed either a sharp drop in activity, or a gradual decrease in activity, corresponding to pushing margins or infiltrative growth of the tumor as was demonstrated by histologic examination of these specimens. Likewise, the shift towards expression of K isozyme of pyruvate kinase in breast cancer compared to normal breast tissue could be demonstrated.

Adult↗
PubMed1988

Glycolytic enzyme activities in breast cancer metastases.

The activities of hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase were studied in breast cancer metastases occurring at various sites and compared with the enzyme activities in a series of primary breast cancers. The activities of all enzymes studied were significantly higher in the metastases compared to the primary tumors (p less than or equal to 0.05). However, no changes in the isoenzyme patterns of enolase and pyruvate kinase were observed when the metastases were compared with primary breast cancers. Differences in location of the metastases did not lead to differences in enzyme activities. Our data suggest an association of an increasing rate of glycolysis with tumor progression.

Aged↗
PubMed1987

Glycolytic enzymes in breast cancer, benign breast disease and normal breast tissue.

The activities of hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase were studied in breast cancer tissues, in comparison to benign breast disease and normal breast tissues. The enzyme activities in breast cancer were significantly increased compared to normal and benign breast tissues (p less than 0.001). Also the increase in activity in benign disease compared to normal was statistically significant (p less than 0.001). Within the group of benign diseases, fibroadenomas could be distinguished from fibrocystic disease, the former generally showing higher activities compared to the latter (p less than or equal to 0.05). Carcinoma subgroups, classified according to their histology, could not be recognized enzymologically. In addition, isozyme composition of pyruvate kinase and enolase was studied. We did not find a significant shift towards K type pyruvate kinase expression in benign disease compared to normal breast tissues. Also fibroadenomas did not differ from fibrocystic disease. However, the amount of K type pyruvate kinase in carcinomas proved to be significantly higher in comparison to benign disease and normal breast tissues (p less than 0.001). Expression of alpha gamma-enolase in normal breast tissue was virtually absent. In benign disease only a minority of specimens did show the hybrid alpha gamma-enolase. Nearly all carcinomas had alpha gamma-enolase expression and in 20% of the carcinomas gamma gamma-enolase could be detected (so-called neuron-specific enolase). By discriminant analysis, the function giving the best discrimination compared to the histological data was based on natural logarithm aldolase and the total of gamma-enolase subunits. Contrary to expectation, the regulator enzymes of glycolysis; i.e., hexokinase, phosphofructokinase and pyruvate kinase were not included in this discriminant function. The best fit produced a 90% correct classification in both benign and malignant disease. If these findings are confirmed to a larger series, the discrimination is sufficiently strong to form the basis of a clinically useful tool.

Biomarkers, Tumor↗
PubMedDate not supplied

Sentinel node biopsies in melanoma patients: a protocol for accurate, efficient, and cost-effective analysis by preselection for immunohistochemistry on the basis of Tyr-PCR.

BACKGROUND: Immunohistochemistry (IHC) of serial sectioning is considered the gold standard for detection of melanoma activity in sentinel node (SN) biopsies. However, this is cost and labor intensive. In contrast, tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) is simple and quick, but it is hampered by its extreme sensitivity. This study was performed to test whether a strategy that combines the two methods, using tyrosinase RT-PCR to preselect nodes for IHC, could be accurate and cost effective. METHODS: In 36 patients, SNs were identified by scintigraphy and patent blue uptake. Of each SN, one cross section was analyzed first by hematoxylin and eosin staining. Next, all nodes were examined by serial sectioning and IHC of one-half and tyrosinase RT-PCR of the other. Before comparison, all results were documented in a blinded manner. Material costs and workload estimates were noted per SN. RESULTS: Fifty-five SNs were retrieved from the 36 patients. Hematoxylin and eosin staining of the first cross section revealed tumor positivity in 3 patients (6 SN). Tyrosinase RT-PCR was positive in 11 of the remaining 33 patients (19 of 49 SN). Of these same 11 patients, only 5 were shown to have tumor-positive SNs by using IHC on serial sections (7 SN). All these nodes had been positive for tyrosinase on PCR. For IHC, an average of 40 sections were prepared and examined per SN at a cost of $200(U.S.)/SN. In contrast, routine tyrosinase RT-PCR costs $37(U.S.)/SN, and takes 5% of the time necessary for IHC. A strategy including hematoxylin and eosin staining on the first cross section, followed by tyrosinase RT-PCR on half of each negative (half) node, could preselect nodes to be taken through serial sectioning. In these series, such a strategy would have prevented serial sectioning and IHC of 30 SN from 22 patients. Apart from a considerable gain in efficiency, this would have reduced material costs by a minimum of $6000 (U.S.). This discrepancy would be even higher if work intensity of analysts and pathologists were considered. CONCLUSIONS: In routine analysis of SN biopsies in melanoma patients, tyrosinase RT-PCR can be used effectively to preselect nodes for further IHC of serial sections. This method seems both time and cost effective.

Biopsy↗
PubMedDate not supplied

Planning of liver surgery using three dimensional imaging techniques.

In the simplified Couinaud classification, in which the liver is divided into eight segments, each supplied by a central vasculo-biliary sheath, little attention is given to the high prevalence of anatomical variations which occur, especially in the right hemiliver. Using volumetric acquisition techniques, such as magnetic resonance imaging or spiral computed tomography scanning, detailed insight into the individual segmental anatomy can now be obtained in a non-invasive manner. The significance of this anatomical insight lies in the planning of anatomical resections, whereby the relationship between tumour and individual segmental anatomy can be depicted in a three-dimensional format. As such, three dimensional (3D) liver imaging helps to design an individualised resection, tailored to the topographical relationship between individual segmental anatomy and tumour tissue present. Three dimensional liver imaging is of most practical value if a resection of one or more segments or sectors is considered, especially in the right hemiliver. In these cases, 3D liver imaging can demonstrate the precise location of the scissuras to the surgeon pre-operatively.

Colorectal Neoplasms↗