大肠癌及癌旁粘膜p21~(ras)表达及意义

应用免疫组织化学方法对 12 8例人大肠癌及 32例不同距离癌旁粘膜进行研究。探讨 p2 1ras检测的临床病理学意义。结果 ,正常大肠粘膜、大肠癌、近癌旁粘膜、癌旁 1cm、2 cm、3cm及 5 cm粘膜 p2 1ras阳性率分别为 5 .0 % (1/ 2 0 )、5 2 .3% (6 7/ 12 8)、2 4.7% (18/ 73)、18.8% (6 / 32 )、15 .6 (5 / 32 )、9.4% (3/ 32 )及 9.4% (3/ 32 )。癌旁 3cm、5 cm粘膜的p2 1ras阳性率、阳性强度及分布均与正常粘膜相似 ,但癌旁 1cm、2 cm粘膜 p2 1ras阳性率较高且其中 5 0 %表达强度为(+ + )、(+ + + ) ,提示有 p2 1ras过表达现象。 p2 1ras表达与大肠癌临床病理因素无关。结论 :大肠癌中存在 p2 1ras过表达 ,且在癌旁 1cm、2 cm以内粘膜也存在 p2 1ras过表达可能 ,因此建议 ,在临床行大肠癌切除时 ,安全切缘至少在 3cm以上。     

Single-agent high-dose melphalan salvage therapy for Hodgkin's disease: Cost, safety, and long-term efficacy

Background: Few data are available on the cost, safety, and long-termefficacy of single agent high-dose melphalan (HDM) followed by autologousbone marrow (ABMT) or blood stem cell (ABSCT) transplantation in the salvagetherapy of Hodgkins disease (HD).Patients and methods: From February 1981 to September 1996, 23 patientswith relapsed (n = 15) or refractory (n = 8) HD received salvage therapywith HDM 140–200 mg/m² followed by non-cryopreservedABMT (n = 18) or cryopreserved ABSCT (n = 5). The cost of HDM/ABSCT in 1996,from initial consultation until transfer back to referring physician, wasdetermined and compared to the estimated costs of two multi-agent regimenscommonly used for HD.Results: HDM was well tolerated with no early transplant-relatedmortality. The five-year overall and progression-free survival rates were52% and 50%, respectively. The average total cost in Canadianfunds of HDM/ABSCT in 1996 was $34,400/patient. This cost wasestimated to be $4,700–6,800 cheaper per patient than themulti-agent high-dose regimens.Conclusion: These data suggest that HDM is safe, feasible, active, andreasonably inexpensive salvage therapy for patients with relapsed/refractoryHD.     

Nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas: Clinical and therapeutic features of 24 localized patients

Background: Peripheral B-cell lymphoma of the marginal zone (MALT, low-grade), presenting as localized, extranodal disease, usually affects the elderly. The gastrointestinal tract is the most frequently involved extranodal location, representing 70% of all MALT lymphomas. Recently, numerous other extranodal sites involved by MALT lymphomas have also been described.Patients and methods: From January 1990 to October 1995, 24 patients with untreated nongastrointestinal low-grade MALT lymphoma were submitted to treatments ranging from the local approach of radiotherapy and local -interferon (-IFN) administration to chemotherapy. The tumours were located in the lung (seven cases), conjunctiva (four cases), lachrymal gland and orbital soft tissue (four cases), salivary glands (three cases), skin (three cases), breast (two cases)' and thyroid (one case). All patients had low-grade stage IE tumours.Results: Chemotherapy was administered in 11 patients (six with lung, three with salivary gland, one with breast, and one with thyroid locations); radiation therapy was employed in seven patients (three with lachrymal gland, three with skin, and one with breast locations); local -IFN administration was administered in five patients (four with conjunctival, and one with lachrymal gland sites); and surgery was employed in one patient with a lung tumour. All patients achieved complete remissions; three local recurrences and two relapses in other sites were observed. The global five-year survival rate was 100% with a relapse-free survival rate of 79%.Conclusions: These data confirm the significant efficacy of different therapeutic approaches to specific sites inbes obtaining a good remission rate for nongastrointestinal localized low-grade MALT lymphomas.     

Effect of irradiation on transforming growth factor-β secretion by malignant glioma cells

Glioblastoma cells secrete transforming growth factor- (TGF-), whichhas a variety of immunosuppressive properties. We investigatedthe effect of irradiation TGF- secretion by malignantglioma cells. Three malignant glioma cell lines (T98G,A172, KG-1-C) were cultured and irradiated using 10and 50 Gy Linac radiation. After further culturefor 36 hours in serum-free culture medium, thesupernatants were collected. The TGF- activity in theculture supernatants was determined using a specific bioassay.The levels of the active form and totalTGF- in the supernatants from irradiated malignant gliomacells decreased compared to those from un-irradiated cells.However, since irradiation inhibited the growth of tumorcells, the amount of TGF- secretion per cellin irradiated cells tended to increase after irradiation.These results suggest that malignant glioma cells canstill secrete TGF- and activate latent TGF- evenafter large dose irradiation, despite the inhibition oftumor growth.     

Purification of thrombospondin from human platelets

Summary Thrombospondins are a rapidly growing family of adhesive proteins that have diverse activities to modulate cellular growth, motility, and gene expression. Thrombospondin-1 (TSP) was the first identified member of this family and is the major form of thrombospondin in human platelets. A method is described to prepare TSP from human platelets in biologically active form with minimal degradation or contamination with other platelet proteins.     

Different types of structural variation in STRs: HumFES/FPS,HumVWA and HumD21S11

Summary Alleles of the STR systems HumFES/FPS, HumVWA and HumD21S11 were sequenced and analyzed. Sequence data revealed 3 different systems concerning the complexity of their sequence structure. HumFES/FPS belongs to the STR polymorphism with a simple repeat structure. Only 2 subtypes were found with a base substitution in the 5-flanking region and no variation in the repeat region. In the STR system HumVWA the sequence structure of the repeat region is more complex, because 2 tetranucleotide units TCTA and TCTG were present. Additionally allele 14 revealed a completely different sequence structure leading to a different electrophoretic mobility. The repeat region of HumD21S11 is compound in structure. The possibility of variation at 3 positions leads to the occurrence of microheterogeneities in fragments of apparent length. In the upper allele range alleles arise with an additional incomplete TA-repeat.     

Presynaptic opioid receptors on dopaminergic nerves in the rabbit caudate nucleus: coupling to pertussis toxin-sensitive G-proteins and interaction with D2 autoreceptors?

Slices of the rabbit caudate nucleus, preincubated with [³H]dopamine and subjected to electrical field stimulation, were used (1) to investigate the involvement of G-proteins in the signal transduction of presynaptic D₂ (auto)receptors and -opioid receptors on dopaminergic axon terminals in this tissue and (2) to study a possible mutual interaction of these two presynaptic receptors. Pretreatment of the slices with either pertussis toxin (8 g/ml; 18 h), or N-ethylmaleimide (30 M, 30 min) significantly reduced the inhibitory effects of both the D₂ agonist quinpirole and the -opioid receptor agonist U-50488H on the [³H]overflow evoked by 36 pulses (2 ms, 24 mA, 0.3 Hz), suggesting the coupling of both receptors to G-proteins.Experiments designed to study possible interactions of these two presynaptic receptors were carried out under stimulation conditions (only 1 pulse), which strongly diminish interference of endogenous transmitters released in the tissue with modulatory effects of exogenous drugs. For instance, due to the presence of endogenous dopamine, quinpirole was much less potent during 36-pulse-than during 1-pulse field stimulation, whereas the D₂ antagonist domperidone was almost without effect in the latter case. Using the 1-pulse stimulation paradigm, the concentration/response curve of quinpirole was unaffected in the presence of the halfmaximal inhibitory concentration of U-50,488 H (0.1 M). On the other hand, also quinpirole at its halfmaximal inhibitory concentration (0.1 M), hardly affected the concentration/response curve of U-50,488 H: only high concentrations of U-50,488 H (above 1 M) seemed to be slightly less effective in the presence than in the absence of the D₂ agonist. U-50,488 H, at these high concentrations, was also less potent under 36-pulse than under 1-pulse stimulation conditions. From these findings, we conclude that there is only a limited interaction between presynaptic D₂ autoreceptors and -opioid receptors on dopaminergic axon terminals in the rabbit caudate nucleus, despite they are both coupled to PTX/NEM-sensitive G-proteins. Correspondence to: R. Jackisch at the above address     

Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus

Vascular smooth muscle contractile responses to neuropeptide Y, ,ß-methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endotheliumin vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1–1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or ,ß-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 ± 14.0%,p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 ± 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus.     

Response of multicellular tumor spheroids to liposomes containing TNF-α

Summary This publication describes a new model to investigate the influence of tumor necrosis factor- (TNF-) on a three-dimensional glial cell aggregate under defined, standardized, reproducible conditions using the glioma cell line A 172.The cells are initially grown as normal monolayer culture until they reach a cell density of up to 1×10⁶. Subsequently they are grown as spheroids by the liquid overlay technique. Spheroids grown in this way were divided into ten groups of more than 50 cell aggregates. Three groups were coincubated with free TNF- in increasing dosages (100 ng/ml, 200 ng/ml and 1000 ng/ml); three groups were incubated with empty liposomes (0.2 mg/ml, 0.4 mg/ml and 2 mg/ml); three groups received liposomes which had been loaded with TNF-, and one group, which received no treatment, served as control.The diameter of the spheroids ranged from 80 m to 350 m. There was no significant difference in growth between the 3 groups treated with free TNF-. Comparing spheroids treated with TNF- with those which had been coincubated with empty liposomes, there was a significant difference (p<0.001) in growth, which correlated with the amount of liposomes. Similarly, free TNF- had a significantly (P<0.001) stronger growth-inhibiting effect as compared to liposomes loaded with TNF-. Comparing the groups treated with liposomes only to those treated with liposomes loaded with TNF-, the latter exhibited a more marked (although not significantly) growth-inhibiting effect.The preliminary conclusion is that the major growth-inhibiting effect seems to be mediated by the liposomes. This phenomenon is in agreement with results obtained in monolayer cultures.