Large cell non-Hodgkin lymphoma of childhood: Analysis of 78 consecutive patients enrolled in 2 consecutive protocols at the Memorial Sloan-Kettering Cancer Center

BACKGROUND: The authors report a study of pediatric patients with advanced diffuse large cell lymphoma (DLCL) who were treated with 2 consecutive regimens, LSA2-L2 and LSA4, over a 25-year-period at the Memorial Sloan-Kettering Cancer Center. They also describe a comparative analysis of two subgroups retrospectively identified as having CD30 positive (+) anaplastic large cell lymphoma (ALCL) and CD30 negative (-) DLCL. To the authors' knowledge, this study represents the longest follow-up on the largest series of uniformly treated pediatric DLCL patients reported to date. METHODS: A total of 78 consecutive patients were treated for Stage III/IV DLCL. Immunophenotypic data were obtained retrospectively for 52 patients using a panel of monoclonal antibodies against CD30, CD15, CD45, CD45Ro, CD43, epithelial membrane antigen, CD5, BCL-2, cyclin-D, and p53. RESULTS: A disease free survival rate of 72% in patients with advanced stage DLCL using the LSA2-L2 and LSA4 regimens. Of the 78 treated patients, 56 are alive and without evidence of disease with a median follow-up of 120 months (range, 24-312 months). The recurrence rate was significantly higher in the CD30+ ALCL subgroup (33%) than in the CD30- DLCL group (0.04%). Of 52 patients for whom immunophenotypic data were available, 28 had disease of B-cell lineage, 24 had disease of T-cell/null phenotype, 19 were CD30+ (36. 5%), 18 had disease of T-cell phenotype, and 1 had disease of B-cell lineage. CONCLUSIONS: The CD30- DLCL cases mostly were of B-cell lineage, had a small risk of treatment failure, and did not develop a recurrence off therapy. A distinct clinical pattern was identified for the CD30+ ALCL group; although these tumors were of T-cell lineage and had a significantly higher rate of late recurrences (median follow-up of 24 months) they all were salvageable. Based on the findings of the current study, the authors propose that T-cell CD30+ ALCL be addressed in the future according to equal dose intensity regimens in induction therapy, as is done for B-cell lymphomas; prolonged periods of maintenance chemotherapy, as is done for T-cell lymphoblastic lymphomas; and no central nervous system prophylaxis beyond the induction period unless other recognized risk factors are present.     

Phenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer

In recent years, significant effort has been made to identify genes that influence breast cancer risk. Because the high-penetrance breast cancer susceptibility genes BRCA1 and 2 play a role only in a small fraction of breast cancer cases, understanding the genetic risk of the majority of breast cancers will require the identification and analysis of several lower penetrance genes. The estrogen-signaling pathway plays a crucial role in the pathophysiology of breast cancer; therefore, polymorphism in genes involved in this pathway is likely to influence breast cancer risk. Our detailed analysis of gene expression profiles of estrogen- and 4-OH-tamoxifen-treated ZR75-1 breast cancer cells identified members of the sulfotransferase 1A (SULT1A) phenol sulfotransferase family as downstream targets of tamoxifen. On the basis of the induction of SULT1A by 4-OH-tamoxifen and the known inherited variability in SULT1A enzymatic activity, we hypothesized that polymorphism in sulfotransferase genes might influence the risk of breast cancer. Using an RFLP that distinguishes an arginine to histidine change in exon 7 of the SULT1A1 gene, we characterized SULT1A1 genotypes in relation to breast cancer risk. An analysis of 444 breast cancer patients and 227 controls revealed no effect of SULT1A1 genotype on the risk of breast cancer (P = 0.69); however, it did appear to influence the age of onset among early-onset affected patients (P = 0.04). Moreover, individuals with the higher activity SULT1A1*1 allele were more likely to have other tumors in addition to breast cancer (P = 0.004; odds ratio, 3.02; 95% confidence interval, 1.32, 8.09). The large number of environmental mutagens and carcinogens activated by sulfotransferases and the high frequency of the SULT1A1*1 allele in human populations warrants additional studies to address the role of SULT genes in human cancer.     

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.     

Allergenic characteristics of chemical compounds migrating from polymer building materials

Methods of determining the allergenic activity of volatile substances given off into the atmosphere from polymer building materials (PBM) are developed. To detect sensitization in experiments on guinea pigs, in vitro allergic diagnostic methods are used (the passive hemagglutination test, specific leukocyte agglomeration test, intensification of leukocyte pyroninophilia test). It is shown that prolonged contact with PBM can give rise to atopic allergic reactions.Medical Institute, Rostov-on-Don. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 2, pp. 202–205, February, 1977.     

Gallium-67 lung uptake: conjugate-view technique

A conjugate-view technique is derived for calculation of absolute gallium-67 (Ga-67) uptake from scintillation-camera images. The technique combines counts of posterior and anterior images of the lung with an attenuation correction obtained from cobalt-57 (Co-57) transmission imaging. The formulation is such that the effects of Compton scatter build-up are accounted for. Studies utilizing a canine model indicated that, normally, more activity is located in the chest wall than in the lungs. The quantitative technique must therefore accurately account for a variety of Ga-67 distributions, including that in the chest wall. Calculations were performed using a three-component model comparing results obtained with the conjugate-view approach to the actual uptake. These calculations suggest that an assumption of uniform activity distribution allows an accuracy of approximately +/- 10% over a broad range of body-part thicknesses and uptake by the lungs. It was concluded that the conjugate-view technique is necessarily approximate but can provide clinically useful results.     

Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive oxygen species and is downregulated by Bcl-2 and antioxidants

S-100 proteins are calcium-binding proteins with important growth regulatory functions. Of these proteins, psoriasin and calgranulin-B have been shown to be highly upregulated in ductal carcinoma in situ (DCIS) of the breast and in psoriasis. The purpose of this study was to further elucidate the functional relevance of the overexpression of these two S-100 proteins in psoriasis and DCIS. We report the induction of both proteins by reactive oxygen species, phorbol ester TPA, and the induction of psoriasin in response to the PI3K inhibitor wortmannin. We also demonstrate that Bcl-2 overexpression represses the induction of psoriasin and calgranulin-B under these different conditions. The same effect was obtained with the antioxidant NAC, which indicates that the suppression of psoriasin and calgranulin-B induction is mediated by the antioxidant function of Bcl-2. Furthermore, we demonstrate that overexpression of a dominant negative IKKbeta also inhibits the induction of psoriasin suggesting that the NFkappaB pathway is involved in the induction of this protein. Also, we found NFkappaB responsive DNA elements in the upstream promoter region of psoriasin. MCF10A cells with a stable retroviral overexpression of psoriasin were significantly more resistant to H2O2-induced cell death than control cells further supporting the hypothesis that these S-100 proteins may play a role in oxidative stress response.     

Platelet Functions in Cardiopulmonary Bypass Surgery

Background

Haemorrhage after Cardio Pulmonary Bypass (CPB) Surgery is a well recognised complication that leads to significant morbidity and mortality. The incidence varies between 5-25% depending upon the clinical situation. Several factors are implicated as causative but none have been precisely proved.

Methods

Our study was an attempt to evaluate the haemostatic defect with particular reference to platelet function abnormalities during cardio pulmonary bypass surgery, in order to reduce the morbidity and mortality associated with post CPB haemorrhage. Flow cytometric evaluation of different platelet glycoproteins like GPIb/IX, GPIIb/IIIa and GMP-140 was done.

Results

The marker expression showed deregulation during surgery which returned to base after bypass was terminated. In contrast, the cases with bleeding showed significant variation. P-Selectin (GMP 140) expression decreased progressively till 3^rd post-operative day showing lack of activation of platelets in cases of severe bleeding.

Conclusion

Longer duration of CPB initiates plasmin generation through heparin, which raises the PAI-1-tPA complex and thereby down regulating the functions of platelets. This suggests a link between duration of CPB, bleeding, platelet dysfunction and fibrinolysis. Hence serial estimations of the levels of GMP-140 and tPA can predict severe bleeding.Key Words: CardioPulmonary Bypass, Platelet dysfunction, flowcytometry, platelet glycoproteins, haemorrhage     

RSA 2004: combined basic research satellite symposium - session four: hepatitis virus and alcohol interactions in immunity and liver disease

This article summarizes the proceedings of the RSA 2004 Combined Basic Research Satellite Meeting convened at the Westin Bayshore Resort and Marina, Vancouver, CA. The session "Hepatitis virus and alcohol interactions in immunity and liver disease" featured four speakers and was chaired by Drs. Diane Lucas and Samuel French. The presentations were 1) Mitochondrial effects of HCV proteins and alcohol by Steve Weinman, 2) Chronic alcohol consumption accelerates viral hepatitis and T-cell hepatitis via dysregulation of cytokine signaling by Bin Gao 3) Interactions between alcohol, hepatitis C virus and innate defense pathways by Steve Polyak and 4) Scavenger Receptor-mediated modulation of the innate and adaptive immune responses following chronic ethanol consumption by Geoffrey Thiele.