Adrenomedullin interacts with VEGF in endometrial cancer and has varied modulation in tumours of different grades.

OBJECTIVE: Endometrial cancer, in developed countries, is the most common malignancy of the female genital tract. Surgery and radiotherapy are successful in many patients but systemic and recurrent diseases have no consistently effective treatments, and for high grade advanced disease the prognosis is poor. The study investigated characteristics of adrenomedullin in endometrial cancer to assist in identifying targets for developing treatments. METHODS: Endometrial samples of women with and without cancer, and the Ishikawa cell line were used to investigate adrenomedullin mRNA regulation, peptide expression, adrenomedullin secretion and effects of adrenomedullin on VEGF secretion. RESULTS: Expression of adrenomedullin mRNA was upregulated compared to that in healthy post-menopausal endometria. Adrenomedullin secretion was increased by cobalt chloride in this study. Secretion was reduced by the naturally-occurring compounds, (-)-epigallocatechin gallate (EGCG) and 3,4',5-trihydroxystilbene (resveratrol), which we have previously demonstrated to also suppress VEGF secretion in endometrial tumour tissue. We noted, for the first time, that adrenomedullin enhanced VEGF secretion from tumour cells. CONCLUSIONS: Increased adrenomedullin expression may result in amplifying both tumorigenic and angiogenic activities. A substantial impact on growth of tumours may result in vivo as a consequence of the synergism between adrenomedullin and VEGF. Adrenomedullin, which has altered cellular characteristics in tumour compared to healthy tissue, offers an understudied target with potential to modify endometrial cancer behaviour, complementing other treatments.

Cellular transfer and AFM imaging of cancer cells using Bioimprint.

A technique for permanently capturing a replica impression of biological cells has been developed to facilitate analysis using nanometer resolution imaging tools, namely the atomic force microscope (AFM). The method, termed Bioimprint, creates a permanent cell 'footprint' in a non-biohazardous Poly (dimethylsiloxane) (PDMS) polymer composite. The transfer of nanometer scale biological information is presented as an alternative imaging technique at a resolution beyond that of optical microscopy. By transferring cell topology into a rigid medium more suited for AFM imaging, many of the limitations associated with scanning of biological specimens can be overcome. Potential for this technique is demonstrated by analyzing Bioimprint replicas created from human endometrial cancer cells. The high resolution transfer of this process is further detailed by imaging membrane morphological structures consistent with exocytosis. The integration of soft lithography to replicate biological materials presents an enhanced method for the study of biological systems at the nanoscale.

Clinicopathological stages and pyrimidine nucleotide synthesis in human mammary carcinomas.

The object of this study was to evaluate activities of thymidylate synthetase (TS) and thymidine kinase (TK) in relation to histopathological features of human mammary carcinomas, as well as clinical classification of patients. The TS and TK are key enzymes on the de novo and salvage pathways, respectively, for pyrimidine nucleotide synthesis. High TS and TK activities have been found in rapidly proliferating tissues. Clinical stage and TNM post-surgical histopathological classification of 20 patients with mammary carcinomas, during the period of 1988-1991, and TS and TK activities in each carcinoma were determined. Elevated TS and TK activities in mammary carcinomas corresponded to progressively worse clinical stages. Papillotubular carcinomas showed lower enzyme activity than that of solid-tubular and scirrhous types. TS activities continued to rise as the malignant invasion became more severe. The clinical prognosis of patients with mammary carcinomas appears to depend on the de novo synthesis of DNA in carcinomas.

Cervical myelopathy caused by the anomalous vertebral artery. A case report.

STUDY DESIGN: A case of cervical myelopathy caused by an anomalous vertebral artery is reported. OBJECTIVES: To report a case of high cervical myelopathy resulting from spinal cord compression by an anomalous vertebral artery. Authors believe that this is the first reported case in which the nutrient artery to the abnormal artery originated from the posterior inferior cerebellar artery. SUMMARY OF BACKGROUND DATA: Although fenestration of the vertebral artery is net an unusual anomaly to the best of the authors knowledge, three cases of high cervical myelopathy resulting from the anomaly were reported. There is no reported case in which an abnormal artery originated from the posterior inferior cerebellar artery. METHODS: The clinical features of the case are reported and discussed with a review of the previously documented cases. RESULTS: The cord compression war relieved surgically, and the patient's symptoms improved postoperatively. CONCLUSIONS: A fenestrated vertebral artery should be included in the differential diagnosis of the upper cervical or the craniovertebral junctional lesions of unknown origin. Magnetic resonance imaging is useful for the diagnosis. In the present case, there was an anomalous branch entered as a nutrient artery from the posterior inferior cerebellar artery. Careful management for similar abnormal arteries includes surgery.

[Experimental and clinical studies on the diagnostic value of CT-myelography using a water-soluble contrast medium, metrizamide].

UNLABELLED: A basic and clinical study on the diagnostic value of computed tomographic myelography (CTM) with metrizamide was performed using the GE. CT/T. X-2. A basic study: using the fourth lumbar spine taken from a fresh cadaver and the phantom containing a test tube filled with metrizamide, the optimum window level (W. L.) and window width (W. W.) of the spinal CT and the optimum metrizamide concentration for the CTM were investigated. A clinical study: the relation between the concentration and volume of metrizamide and the timing for performing the CTM after intrathecal injection of metrizamide were examined, then CTM was performed in 82 cases with spinal and spinal cord disorders and 4 cases with normal spinal cords. RESULTS: 1) Observing the spinal CT and CTM, the optimum W. L. is 50-150 and W. W. is 1,000. 2) The optimum metrizamide concentration of the subarachnoid space for CTM is 6-12 mgI/ml and its CT number is 150-300. This concentration is difficult to recognize in the conventional myelography. 3) It was confirmed that there were two methods to obtain the optimum concentration. One is the CTM after conventional myelography by lumbar puncture; at the cervical or thoracic level CT is performed 1-2 hours after metrizamide myelography with 230-250 mgI/ml and 7-10 ml, and at the lumbar level CT is performed 3-6 hours after myelography with 190-200 mgI/ml and 6-7 ml. The other is the CTM without conventional myelography; at each level, metrizamide with 100 mgI/ml is injected by lumbar puncture and CT is performed 15-40 minutes after injection of 10-15 ml for the cervical or thoracic level, and 3-5 ml for the lumbar level. The CTM obtained under these conditions provides the accurate information about intraspinal canal lesions and, therefore, it is very useful not only for the diagnosis of the lesion but also for the selection of the approach when a surgical treatment is indicated.

Defects in yeast RNA polymerase II transcription elicit hypersensitivity to G1 arrest induced by Kluyveromyces lactis zymocin.

The G1 cell cycle arrest imposed by Kluyveromyces lactis zymocin on Saccharomyces cerevisiae requires a functional RNA polymerase II (pol II) TOT/Elongator complex. In a study of zymocin's mode of action, genetic scenarios known to impair transcription or affect the pol II machinery itself were found to elicit hypersensitivity to zymocin. Thus, mutations in components of SAGA, SWI/SNF, Mediator and Ccr4-Not, complexes involved in transcriptionally relevant functions such as nucleosome modification, chromatin remodelling and formation of the preinitiation complex, make yeast cells hypersensitive to the lethal effects of zymocin. The defects at the level of transcriptional elongation displayed by rtf1Delta, ctk1, fcp1 and rpb2 mutants also result in zymocin hypersensitivity. Intriguingly, inactivation of histone deacetylase (HDAC) activity, which is expected to reduce the demand for the histone acetyltransferase (HAT) function of TOT/Elongator, also reduces sensitivity to zymocin. Thus, zymocin interferes with pol II-dependent transcription, and this effect requires the HAT function of TOT, presumably while the Elongator complex is associated with pol II.