Tumor angiogenesis and metastasis: correlation in invasive renal cell carcinoma

BACKGROUND: Experience suggests that tumor growth is dependent on angiogenesis. The intensity of angiogenesis in human cancer is reported to be predictive of the probability of metastasis in many types of cancer. The aims of this study were 1) to determine the relationship of microvessel density (MVD) in renal cell carcinoma to pathologic stage, and 2) to evaluate the role of MVD in metastasis. METHODS: Paraffin-embedded tumor specimens were reviewed from 34 unselected patients with RCC who had undergone surgery from 1986 to 1990 at Taichung Veterans General Hospital. The pathology findings and clinical records were reviewed to note relationships between pathologic stage and whether or not metastasis had occurred. Specimens were studied from 16 cases (eight Stage I cancers, five Stage II and three Stage III) without metastasis and from 18 cases (two Stage I, six Stage II, six Stage III and four Stage IV) in which metastasis later developed. Microvessels were highlighted by immunostaining endothelial cells for factor VIII-related antigen. Microvessels were counted in a x-400 field (0.1885 mm2/field) in the most active areas of neovascularization. RESULTS: The 16 patients without metastasis have survived for between 65 and 136 months (mean, 94.5 months), up to the present time. Of the 18 patients with metastasis, 15 died and three survived, with mean survivals of 42.8 months (range, 12-99 months). Mean overall MVD was 99.6 vessels; mean MVD was 98.5, 96.2, 109.3 and 90.0 in Stages I, II, III and IV tumors, respectively. Mean MVD was 99.3 in patients without metastasis and 99.9 in patients with metastasis. CONCLUSIONS: MVD does not correlate with pathologic stage and is of no prognostic significance in renal cell carcinoma.     

Malignancy may adversely influence the quality and behaviour of oocytes

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age-matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.     

Controlling Hamiltonian chaos

A 50-year-old woman underwent excision of a vaginal cyst. Its distal end lay in the submucosal tissue of the posterior lateral aspect of the vulvar vestibule near the orifice of Bartholin's gland. The caudal wall of the cyst contained a papilloma with an epithelial lining which consisted of columnar and stratified polygonal cells resembling squamous and transitional epithelium. The histochemical attributes of the papillary epithelium were homologous to those of Bartholin's gland. Immunohistochemical studies supported glandular and squamous differentiation. Evolution from a dysontogenetic remnant of Müllerian origin cannot be excluded with certainty, but location and histopathology were consistent with origin from Bartholin's gland duct. The presence of mucin and the absence of a smooth muscle investment exclude derivation from Gartner's duct. Cysts of Bartholin's gland are common, but solid benign tumors are rare. We have been unable to find a report of a papilloma of either vulva or vagina with features similar to those in our patient.     

Diversity of cDNAs encoding phospholipase A2 from Agkistrodon halys pallas venom, and its expression in E. coli

As a step toward understanding the structure and function of phospholipase A2(PLA2), we isolated several novel cDNAs encoding Agkistrodon halys Pallas PLA2 isoenzymes including B-PLA2, Asn49-PLA2, A-PLA2, A'-PLA2 and BA1-PLA2 by polymerase chain reaction with oligonucleotide primers corresponding to the N- and C-terminus of these enzymes. The amino acid sequences of A-PLA2 deduced from cDNA are consistent with that isolated from venom except for four residues. Asn49-PLA2 and B-PLA2 are highly similar (> 95%), but the critical residue Asp49 in the active centre of B-PLA2 is replaced by Asn49 in Asn49-PLA2. The N-terminal residues (1-24) of BA1-PLA2 shows high similarity to that of B-PLA2 which has strong ability to hemolyze erythrocytes, while its C-terminal residues (72-125) are the same as that of A-PLA2 which can inhibit platelet aggregation. The successful cloning of these isoenzymes not only provide excellent native material to study the structure-function relationship of PLA2s, but also to disclose the genesis of structural diversity of PLA2s, namely DNA modification and gene rearrangement. The cloned cDNA for A-PLA2 has been expressed in E. coli. By Q-Sepharose column chromatography, denaturation-renaturation and FPLC, we obtained the active recombinant protein with the initiator Met. This is the first report of the production of an active recombinant PLA2 with the initiator Met.     

Computational methods in molecular diversity and combinatorial chemistry

(+)-MK-801 is known to be a specific non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors. However, besides having an anticonvulsant effect, this compound possesses a central sympathomimetic effect and an anxiolytic-like action, raising the possibility that (+)-MK-801 might affect monoamine uptake systems. To elucidate this possibility, we investigated the effects of (+)-MK-801 on monoamine transporters expressed in HEK cells. (+)-MK-801 significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner and the inhibitions were competitive with respect to monoamines. The Ki values of (+)-MK-801 on the norepinephrine, dopamine and serotonin transporters were 3.2 microM, 40 microM and 43 microM, respectively. In addition, (-)-MK-801, a less potent antagonist of NMDA receptors, also inhibited monoamine transporters with a similar potency as that of (+)-MK-801. These results clearly indicate that MK-801, a non-competitive antagonist of NMDA receptors, competitively inhibits monoamine transporters without stereoselectivity.     

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.     

Using titanium plate or meshplate for chest wall reconstruction: report of 6 cases and literature review

Titanium plate has been widely used in several surgical fields, such as craniofacial reconstruction and orthopedic prosthesis. This prosthesis has been proved not only with good biocompatibility and mechanical strength, but also with light weight and low radiological interference. From October 1991 to May 1995, 6 patients underwent thoracic cage reconstruction with titanium plate in our hospital. They included 5 females and 1 male, with ages ranging from 26 to 62 years. Four of them suffered from primary chest wall tumors (2 desmoid tumors, a chondrosarcoma, and 1 hemangioma), one had a recurrent chest wall tumor from breast carcinoma, and one had thoracic hypoplasia. The thoracic cage defect ranged from 5 x 6 cm to 10 x 15 cm, and 1 to 3 titanium plates were used for the reconstruction. No paradoxical movement or other prosthesis-related complications have occurred during the follow-up period. We conclude that titanium plate is a good material for thoracic cage reconstruction.