防御素的抗肿瘤研究

当代肿瘤的治疗仍有许多问题未能解决防御素引入肿瘤墓因治疗已成为一个有前景的新途径.防御素(defensins)是存在于哺乳动物多形核中性粒细胞、巨噬细胞、小肠Peneth细胞中的一组同源性很高的生物多肤类,由29一34     

Strengthen international academic exchange and promote development of gastroenterology

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Accuracy of CT-guided biopsies in 158 patients with thoracic spinal lesions

Objective： To determine the accuracy of CT-guided thoracic spinal biopsy, to compare the results with those previously reported, and to determine if there are any factors that influence the accuracy of CT-guided thoracic spinal biopsy. Methods： In total, 158 consecutive CT-guided percutaneous thoracic spine procedures （performed at our hospital between April 2000 and July 2010） were reviewed. The 158 lesions were categorized by location and radiographic features. Pathological and clinical follow-up were used to determine accuracy. Results： The diagnostic accuracy of CT-guided thoracic spinal biopsy was 90.5% overall. Biopsy of metastatic bone disease （98.2%） was significantly more accurate than biopsies of primary tumors （80.9%） and of hematological malignancies （47.0%） （P〈0.05 and P〈O.005, respectively）. The diagnostic accuracy of CT-guided thoracic spinal biopsy was significantly higher for the lower thoracic spine （97.6%） than for the middle （90.0%） or upper thoracic spine （80.4%） （P〈0.05 and P〈0.025, respectively）. The diagnostic accuracy was significantly higher for lytic lesions （96.4%） than for sclerotic lesions （81.3%） （P〈0.010）. The accuracy of biopsies performed using the transpedieular approach （91.0%） was not significantly different from that of biopsies performed using posterolateral approaches （91.5%） （0.25〈P〈0.5）. Conclusion： Percutaneous CT-guided thoracic spinal biopsy is a viable alternative to open surgical biopsy. The diagnostic accuracy was not affected by any of the variables except for lesion level, histology, and radiographic features.     

Improving outcomes for high-risk DLBCL: a pilot study looking at the role of fractionated cyclophosphamide with RCHOP chemo-immunotherapy (SCUBA-1 trial)

The outcomes for patients with high-risk DLBCL are suboptimal, especially in Low-middle income countries in comparison to published data from the western world. Most newer therapies aimed at improving outcomes are either unavailable or out of reach for the majority of patients in low-middle income countries. Cyclophosphamide is an easily available and accessible drug that forms the backbone for therapy for DLBCL. We conducted a single-center, open-label randomized pilot study comparing standard RCHOP to RCHOP with fractionated cyclophosphamide (RfCHOP) in patients with newly diagnosed, high-risk DLBCL. Fifty-five patients were randomized- 28 to RfCHOP and 27 to the RCHOP arm. RfCHOP was associated with a higher complete response rate than RCHOP at the end of 6 cycles of therapy (81.2% vs. 59.3%; p-0.062). Grade III/IV adverse events were comparable in both arms with the use of prophylactic GCSF in the RfCHOP arm. At a median follow-up of 22 months, the Median EFS and OS was not reached in either arm. RfCHOP may represent a therapeutic option for patients with newly-diagnosed, high-risk DLBCL, especially in Low-middle income countries. Larger studies are required to confirm these findings.     

In vitro characteristics of white cell-reduced single-unit platelet concentrates stored in syringes

BACKGROUND: Platelet concentrates (PCs) for premature infants may be subjected to filtration, centrifugation, and various storage conditions before transfusion. STUDY DESIGN AND METHODS: As there are few data on the cumulative effect of these procedures on PCs, platelet properties (including biochemical and functional in vitro assays) were evaluated after the processing of single units of PCs through a 1-unit-capacity high-efficiency white cell (WBC)-reduction filter followed by syringe storage at either 22 or 37 degrees C for 6 hours. Two- and 5-day-old PCs, volume-reduced PCs, and prestorage WBC-reduced PCs were evaluated. RESULTS: WBC filtration consistently resulted in a 3 to 4 log10 reduction in WBCs, with less than 15-percent platelet loss. No adverse effects of platelet function or evidence of increased platelet activation as determined by the percentage of P-selectin positivity were noted. A decrease in pH associated with increased lactate production and consumption of glucose was observed following syringe storage under all conditions tested. Such changes were most pronounced, however, with volume-reduced PCs stored at 37 degrees C (pH 6.31 +/− 0.15, lactate 23.0 +/− 3.06 mmol/L). All pH levels at the end of storage were above the minimum Food and Drug Administration requirement (pH 6.0). CONCLUSION: The in vitro data suggest that single units of PCs can undergo WBC filtration followed by syringe storage for up to 6 hours and still maintain acceptable storage characteristics. The practice of maintaining volume-reduced PCs in syringes for 6 hours at 37 degrees C in isolettes during transfusion should, however, be avoided.     

Interleukin-10 administration decreases survival in murine recipients of major histocompatibility complex disparate donor bone marrow grafts

Studies in mice and humans have indicated that the predominance of interleukin-4 (IL-4)- and IL-10-producing T-helper type 2 (Th2) cells may serve to downregulate acute graft-versus-host disease (GVHD) reactions, whereas IL-2-producing Th1 cells have been implicated in facilitating acute GVHD. We explored the possibility that the in vivo infusion of IL-10 would inhibit acute GVHD induced by fully allogeneic donor grafts. Unexpectedly, IL-10 infusions resulted in a dose- dependent increase in GVHD-induced mortality. The acceleration of lethal GVHD by IL-10 occurred in irradiated recipients of T-cell- depleted bone marrow (BM) plus 5, 15, or 25 x 10(6) splenocytes but did not influence the post-BM transplantation (post-BMT) survival rate of recipients of BM without splenocytes, suggesting that the IL-10 effects were not due to toxicity. Antimurine IL-10-neutralizing monoclonal antibody injections, administered to diminish endogenous IL-10, reduced GVHD-associated mortality and improved the clinical appearance of the recipients. For BM graft rejection studies, IL-10 was infused into sublethally irradiated recipients of anti-Thy 1.2 + C' T-cell-depleted, fully allogeneic BM grafts. In a short-term (day 7) in vivo assay, IL- 10 infusions significantly inhibited allogeneic (but not syngeneic) BM proliferation in vivo, indicative of increased graft rejection. In long- term chimerism experiments, IL-10 infusions caused a significant increase in early post-BMT mortality caused by a profound anemia typically associated with graft rejection and aplasia. A slightly higher irradiation dose (650 cGy v 600 cGy) eliminated the anemia but did not reverse the graft rejection process associated with IL-10 administration. We conclude that the in vivo infusion of exogenous IL- 10 in recipients of fully allogeneic donor grafts results in accelerated GVHD and graft rejection in the strain combinations tested to date.     

Unrelated donor bone marrow transplantation: influence of HLA A and B incompatibility on outcome

We have studied the outcome of 211 consecutive unrelated donor (URD) bone marrow transplants (BMT) performed at the University of Minnesota (Minneapolis, MN) between May 1985 and December 1992. Ninety patients (43%) received marrow matched serologically at HLA A, B, and DR loci; 86 (41%) received marrow with a major and 32 (15%) marrow with a minor serologic mismatch at the HLA A or B locus. Multivariate analysis revealed that older age had an adverse effect on survival. In younger (age less than 18 years) recipients, survival after fully matched (A, B, and DR sub-type) or major mismatched (A or B locus), DR subtype- matched donor BMT was not significantly different (P = .4; survival: 53% v 41%, respectively, at 3 years). For adults, survival after matched donor BMT was significantly better than that with mismatched donors (P < .01; survival: 30% v 10%, respectively, at 3 years). Formal quality of life assessment by telephone interview demonstrated similar functional status in survivors of URD and related donor (RD) BMT at least 2 years post-BMT. URD BMT provides effective therapy for a variety of lethal hematopoietic diseases that rivals outcome of RD transplant in some cases. Use of URD marrow with a major mismatch at one HLA A or B locus is well tolerated in young, but not in older, recipients. These observations should be used to improve donor selection and counseling for URD BMT candidates.