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Biomedical subjects

J W Ho

Publications and source records attributed to J W Ho.

At least 19 recordsLinked to original sources
PubMed2006

Rapamycin attenuates liver graft injury in cirrhotic recipient--the significance of down-regulation of Rho-ROCK-VEGF pathway.

To investigate whether rapamycin could attenuate hepatic I/R injury in a cirrhotic rat liver transplantation model, we applied a rat orthotopic liver transplantation model using 100% or 50% of liver grafts and cirrhotic recipients. Rapamycin was given (0.2 mg/kg, i.v.) at 30 min before graft harvesting in the donor and 24 h before operation, 30 min before total hepatectomy and immediately after reperfusion in the recipient. Rapamycin significantly improved small-for-size graft survival from 8.3% (1/12) to 66.7% (8/12) (p = 0.027). It also increased 7-day survival rates of whole grafts (58.3%[7/12] vs. 83.3%[10/12], p = 0.371). Activation of hepatic stellate cells was mainly found in small-for-size grafts during the first 7 days after liver transplantation. Rapamycin suppressed expression of smooth muscle actin, which is a marker of hepatic stellate cell activation, especially in small-for-size grafts. Intragraft protein expression and mRNA levels of vascular endothelial growth factor (VEGF) were down-regulated by rapamycin at 48 h both in whole and small-for-size grafts. Consistently, mRNA levels and protein expression of Rho and ROCK I were decreased by rapamycin during the 48 h after liver transplantation. In conclusion, rapamycin attenuated graft injury in a cirrhotic rat liver transplantation model by suppression of hepatic stellate cell activation, related to down-regulation of Rho-ROCK-VEGF pathway.

Actins↗
PubMed2001

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗
PubMed2001

Early-onset colorectal cancer with stable microsatellite DNA and near-diploid chromosomes.

Colorectal cancer has been described in terms of genetic instability selectively affecting either microsatellite sequences (MIN) or chromosome number and structure (CIN). A subgroup with apparently stable, near-diploid chromosomes and stable microsatellites (MACS) also exists. These distinctions are important, partly because of their value in highlighting different pathways of carcinogenesis, and partly because of their direct relevance to prognosis. Study of early-onset cancer has often proved a fruitful resource for the identification of the nature and function of cancer susceptibility genes. In a study of colorectal cancer with stable microsatellite DNA, we describe 22 early-onset tumours (mean age=33), compared with 16 late-onset tumours (mean age=68). Both groups contained carcinomas with the MACS phenotype, characterized by near diploid DNA content, as defined by flow cytometry, and minimal chromosome arm deletion or amplification (six or less events per genome), determined by comparative genomic hybridization (CGH). Minimal chromosome imbalance correlated strongly with diploid DNA content (P<0.001). The proportion of MACS cancers was significantly greater in early-onset as compared to late-onset tumours (64 vs 13%, P=0.005). Of the chromosome arm imbalances commonly observed in late-onset tumours, only 18q- was observed more than twice amongst the 14 early-onset MACS tumours. Seventy-nine per cent of these MACS tumours were located in the distal colon, and 69% were at advanced clinico-pathological stages (with lymph node or distant metastasis). A positive family history of colorectal or other cancers was elicited in seven patients in the MACS early-onset group, and one additional patient in this group had a metachronous ovarian cancer. The results suggest that MACS cancer may have a genetic basis different from either MIN or CIN, and further studies of these cancers may lead to discovery of new mechanisms of colorectal carcinogenesis and cancer susceptibility.

Aged↗
PubMed2001

A novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: a founder mutation in the Chinese population.

We have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It is well known that alternative splicing is common in hMLH1, which complicates RNA based mutation detection methods. In contrast, large deletions in hMLH1, commonly observed in some ethnic groups, tend to escape detection by exon-by-exon direct DNA sequencing. Here we report the detection of a novel germline 1.8 kb deletion involving exon 11 of hMLH1 in a local hereditary non-polyposis colorectal cancer family. This mutation generates a mRNA transcript with deletion of exons 10-11, which is indistinguishable from one of the most common and predominant hMLH1 splice variants. A diagnostic test based on PCR of the breakpoint region led to the identification of an additional young colorectal cancer patient with this mutation. Haplotype analysis suggests that they may share a common ancestral mutation. Our results caution investigators in the interpretation of alternative splicing and have important implications for the design of hMLH1 mutation detection strategy in the Chinese population.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Purification and characterization of multiple glutathione S-transferase isozymes from Chironomidae larvae.

Glutathione S-transferase (GST) has been implicated in the process of biotransformation of polycyclic aromatic hydrocarbons and of other organic pollutants by Chironomidae larvae. We have purified and characterized GST from cytosolic fractions of Chironomidae larvae. GST with an M(r) of 23 kDa has been purified to homogeneity from larvae by centrifugation, size exclusion chromatography on Sephadex G25, and glutathione affinity and anion exchange chromatography. The purified enzyme exhibited moderate activity towards 1,2-dichloro-4-nitrobenzene, 1-chloro-2,4-dinitrobenzene, 4-nitropyridine-N-oxide, p-nitrobenzyl chloride, ethacrynic acid, and cumene hydroperoxide. The enzyme was homogeneous on gel isoelectric focusing and on SDS gel electrophoresis. Its isoelectric point was estimated to be 5.5. The enzyme had a maximum activity at approximately pH 8 and showed activity between 30 and 40 degrees C. It became inactive at higher temperature (>50 degrees C) for 5 min. The N-terminal sequence analysis of the amino acids shows a high % of conserved regions in the enzyme. The enzyme activity was comparable to levels of metabolism observed by animal GST involved in the detoxification of xenobiotics.

Amino Acid Sequence↗
PubMed2001

Purification and properties of ferrochelatase from Chironomidae larvae.

Ferrochelatase with an Mr of 42,700 Da and a pI of 7.35 has been purified to homogeneity from chironomidae larvae. The activity of the enzyme reached maximum at pH 7.8 and decreased with the increase of pH. The enzyme activity varied with temperature and showed maximum activity around 37 degrees C. The purified enzyme was active towards protoporphyrin but inactive towards other porphyrins. The specific enzyme activity of ferrochelatase from chironomidae is about 10-fold higher than that of the rat. Electrophoresis of the purified fractions shows that the enzyme contains only one single polypeptide. The soluble ferrochelatase contained one mole of iron in each mole of the enzyme. The N-terminal sequence analysis of the enzyme shows a high percentage of conserved regions of the enzyme among other species. The enzyme properties are similar to those of the mammalian ferrochelatases except with slightly higher specific activity. Chironomidae ferrochelatase appeared to be more heat resistant and less susceptible than its mammalian equivalent to inhibition by lead.

Amino Acid Sequence↗
PubMed2001

Radiation recall with oxaliplatin: report of a case and a review of the literature.

Oxaliplatin is a new platinum derivative that has significant activity in patients with metastatic colorectal carcinoma. Some of these patients may have been previously treated with radiotherapy. The interaction of radiotherapy with oxaliplatin needs to be further studied. We report a patient with advanced colonic carcinoma who was treated with concomitant chemoirradiation with oxaliplatin and developed a peculiar dermnatitis in the irradiated field after being exposed to subsequent chemotherapy with oxaliplatin.

Antineoplastic Agents↗
PubMed2001

Effects of vitamins and common drugs on reduction of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rat microsomes.

4-(Methylnitrosamino)-1-(3-pyridyl)-butanone (NNK) is a tobacco-specific nitrosamino that requires metabolic activation by cytochrome P450 enzymes. The activation of NNK by cytochrome P450 enzymes leads to the formation of different metabolites. Detoxification of NNK usually occurs via carbonyl reduction to its hydroxyl product, 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL). In the present study, the influences of common vitamins and P450 modulators on the reduction of NNK by rat microsomes were studied. The formation of NNAL but not other metabolites was detected by the described HPLC method. Among the vitamins tested, vitamins E, A (retinol), B6 and B5 were found to be marginal effective upon reduction of NNK while vitamins A (cis-acid), A (trans-acid), D2, D3, K1, K3, B1 and A (crocetin) increased the formation of NNAL from 3 to 21%. The effect of vitamin C-palmitate (<10 microM) was most pronounced followed by crocetin upon reduction of NNK. Clonidine, tolbutamide and atropine slightly increased the reduction of NNK while cimetidine showed no effects. The modulation of NNK reduction could reduce the carcinogenic potential of NNK, since the main detoxification pathway of NNK involves carbonyl reduction.

Adrenergic alpha-Agonists↗
PubMed2000

Chromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutation.

We have previously reported high-frequency microsatellite instability (MSI-H) and germ-line mismatch repair gene mutation in patients with unusually young onset of high-grade glioma. Some of these patients developed metachronous MSI-H colorectal cancer and conformed to the diagnosis of Turcot's syndrome. Frameshift mutation of TGFbetaRII was present in all the colorectal carcinomas but not in brain tumours. We further characterized the genetic pathways of tumour evolution in these metachronous gliomas and colorectal carcinomas. All MSI-H glioblastomas had inactivation of both alleles of the p53 gene and showed over-expression of the p53 protein while none of the colorectal carcinomas had p53 mutation or protein over-expression. Flow cytometry and comparative genomic hybridization revealed that all glioblastomas were chromosomal unstable with aneuploid DNA content, and with a variable number of chromosomal arm aberrations. In contrast, the colorectal carcinomas had diploid or near-diploid DNA content with few chromosomal arm aberrations. The pattern of chromosomal aberrations in the two organs was different. Loss of 9p was consistently observed in all glioblastomas but not in colorectal carcinomas. Epidermal growth factor receptor amplification was absent in all glioblastomas and colorectal carcinomas. Our results suggest that both the frequency of p53 mutation and its effects differ greatly in the two organs. Following loss of mismatch repair function, p53 inactivation and chromosomal instability are not necessary for development of colorectal carcinoma, but are required for genesis of glioblastoma. Oncogene (2000) 19, 4079 - 4083.

Adenocarcinoma↗
PubMed2000

Distinct clinical features associated with microsatellite instability in colorectal cancers of young patients.

The Hong Kong Chinese population has an unusually high incidence of colorectal cancer in the young, suggestive of hereditary susceptibility. To search for a genetic basis for this predisposition, we studied the incidence of microsatellite instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50 years old) Chinese colorectal cancer patients referred to the Hong Kong Hereditary Gastrointestinal Cancer Registry from 1995 to 1998. By medical record review and personal interview, we searched for distinct clinical features associated with the manifestation of MSI in this group of patients. For patients with MSI tumours, blood was taken for detection of germline mutation in 2 mismatch repair (MMR) genes. MSI was present in 33 tumours from 23 males and 10 females (26.6%). Ongoing mutation analysis has so far identified MMR gene mutations in 8 patients with MSI tumours. The incidence of MSI increased significantly with decreasing age at cancer diagnosis. For patients aged 30 to 49, MSI tumours were located mainly at the proximal colon. However, for exceptionally young patients (<30 years), MSI tumours tended to be at the distal large bowel. This observation suggested a differential activity of the MMR pathway in colorectal carcinogenesis in different age groups. On multivariate analysis, young age at cancer diagnosis, proximal tumour location, a strong family history of colorectal cancer, and a personal history of metachronous cancer were independent predictors for MSI status. This knowledge may have an impact on the management of young colorectal cancer patients and their families.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Self-expanding metallic stent in the treatment of colonic obstruction caused by advanced malignancies.

INTRODUCTION: The treatment of malignant obstruction of the left colon or rectum usually requires emergency surgery on poor-risk patients, and the creation of a stoma is usually inevitable. With the use of self-expanding metallic stents, the prompt relief of large-bowel obstruction without surgery has become possible. This report describes our results in the use of self-expanding metallic stents in the treatment of left-sided colonic obstruction resulting from advanced malignancies. METHODS: From November 1997 to March 1999, insertion of self-expanding metallic stents was attempted in 24 patients with acute left-sided colonic obstruction caused by primary or recurrent malignancies. All the procedures were performed by colorectal surgeons. The guidewire was inserted through the channel of the endoscope, and its position was confirmed with fluoroscopy. Uncovered Wallstent esophageal endoprostheses were used in all except the first case. The insertion and deployment of the stents were under both endoscopic and fluoroscopic guidance. RESULTS: There were 24 patients (15 males) with a mean age of 63.6 (range, 36-98) years. Thirteen patients had primary colorectal cancer and 11 had recurrent cancers (colorectal cancer, 5; gastric cancer, 5; other, 1). In the treatment of primary colorectal cancer, seven procedures were palliative, and no subsequent surgery was planned because of extensive liver metastasis or poor medical risk. The other six patients underwent elective resection after mechanical bowel preparation. There was no mortality related to the procedure. Stenting was successful in the relief of obstruction in 23 patients. Perforation of the colon occurred in one patient, and an emergency Hartmann's operation was performed. Migration of the stents occurred in three patients. Only 3 of the 18 patients in the palliation group required the subsequent creation of stomas. CONCLUSION: The use of the self-expanding metallic stents can achieve rapid and effective nonsurgical means to relieve left-sided colonic obstruction. It provides good palliation for unresectable advanced tumors that cause colonic obstruction. It may also have a role in the temporary relief of obstruction so that subsequent colonic resection can be performed under elective conditions.

Adult↗
PubMed2000

Risk factors for anastomotic leakage after low anterior resection with total mesorectal excision.

BACKGROUND: This study aims to analyze the risk factors for anastomotic leakage after low anterior resection with the technique of total mesorectal excision (TME). METHODS: From September 1993 to November 1998, 196 patients with rectal cancer from 3 to 12 cm from the anal verge were treated with low anterior resection with TME. The data were entered in a prospective manner, and the factors that might affect anastomotic leakage were analyzed. RESULTS: The mean level of anastomosis was 3.6 cm from the anal verge (range 1 to 5 cm). The leakage rate was 10.2%. Female gender (P = 0.01; 95% confidence interval [CI] 1.3 to 14.3; odds ratio 4.3) and presence of a diversion stoma (P = 0.01; 95% CI 1.4 to 14.2; odds ratio 4.5) were independent significant factors for lower anastomotic leakage. The absence of a stoma was associated with significantly increased leakage in male (P = 0.001) but not in female (P = 0.51) patients. CONCLUSIONS: With low anastomosis after low anterior resection with TME, diversion stoma construction should be performed routinely in men. In women, the need for diversion can be more selective.

Adult↗
PubMed1999

Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer.

BACKGROUND: The incidence of colorectal cancer in persons under 46 years of age is substantially higher in Hong Kong than in Scotland and many other countries. Consequently, we examined whether there is a hereditary predisposition for colorectal cancer in this Southern Chinese population. METHODS: We investigated the incidence of microsatellite instability (MSI) at 10 DNA sites in 117 colorectal cancer specimens from Chinese patients of various ages. Those tumors with new alleles at 40% or more of the sites investigated were identified as highly unstable MSI (MSI-H). In young patients, we also searched for germline mutations in three mismatch repair genes (hMSH2, hMLH1, and hMSH6). RESULTS: The incidence of MSI-H varied statistically significantly with age, being observed in more than 60% of those younger than age 31 years at diagnosis and in fewer than 15% of those age 46 years or older. In 15 patients (<46 years old) whose colorectal cancers showed MSI-H, eight possessed germline mutations in either hMSH2 or hMLH1. When mutations in hMSH6 were included, more than 80% of Chinese colorectal cancer patients younger than 31 years had germline mutations in mismatch repair genes. We found a novel germline missense mutation in hMSH6 in a 29-year-old man whose tumor showed no MSI. Two patients had a 4-base-pair insertion in exon 10 causing a truncated protein; this insertion is a common polymorphism with a population allele frequency in Chinese of 5.6%. CONCLUSIONS: Our results indicate that germline mutations in mismatch repair genes contribute substantially to the pathogenesis and high incidence of colorectal cancer in young Hong Kong Chinese. However, because young Chinese and Caucasians show similar proportions of colorectal cancers with MSI-H, despite the higher incidence in the former, additional factors may underlie the high susceptibility of young Chinese to colorectal cancer.

Adenocarcinoma↗
PubMed1999

Preferential type 1-1 cytokine gene expressions in peripheral T-cell lymphomas.

In this study, we have investigated whether a pattern of cytokine gene expression can be found in non-Hodgkin's peripheral T-cell lymphoma (PTCL). By using RNase protection assays and RT-PCR, we have systematically studied IL1alpha, IL1beta, IL1-Ra, IL2, IL4, IL5, IL6, IL9, IL10, IL12p35, IL12p40, IL13, IL14, IL15, IFNgamma, IFNbeta, TNFalpha, TNFbeta, LTbeta, and TGFbeta1, TGFbeta2 and TGFbeta3. Twenty-two cases of PTCL inclusive of three nasal NK-cell lymphomas were selected for the study; three cases of reactive lymphoproliferation were included for comparison. Results show that IFNgamma gene expression (key Type 1 cytokine) was frequently detected [18/22 (82 per cent)]. In contrast, IL4 (key Type 2 cytokine) was only detected in 4/22 (18 per cent) of cases (weaker than IFNgamma in three cases). This distinction was also found at the protein level by immunohistochemistry. In addition, TNFbeta and TNFalpha (strongly expressed by Type 1 cells) were almost complimentarily detected [4/19 (21 per cent)] and 12/19 (63 per cent), respectively). In contrast, neither IL5 nor IL13 (strongly expressed by Type 2 cells) were detected at all. However, 14/22 cases expressed IL10, another Type 2 cytokine, which suggests that the autoregulatory feedback loop is stimulated. Compared to the tumour types, the cytokine profiles in the reactive lymphoproliferative types also resembled a Type 1-like pattern but was less striking. The overall result suggested a preferential expression of certain cytokines, and these cytokines may play an important role in pathophysiologic progression in these T-cell disorders.

Cytokines↗
PubMed1999

Prospective evaluation of selective defunctioning stoma for low anterior resection with total mesorectal excision.

Low anterior resection with total mesorectal excision for rectal carcinoma is associated with a high anastomotic leakage rate, and the effectiveness of a defunctioning stoma in preventing anastomotic leakage remains controversial. In this study a policy of selective defunctioning stoma for stapled colorectal anastomosis after low anterior resection with total mesorectal excision in 148 consecutive patients was evaluated prospectively. A defunctioning stoma was performed in 61 patients (41%) considered at high risk of anastomotic leakage. Clinical leakage occurred in 2 patients (3.3%) with a stoma and 11 patients (12.6%) without a stoma (p = 0.047). Among those without a stoma, the leakage rate among male patients (20.9%) was significantly higher than that for female patients (4. 5%) (p = 0.022). Leakage subsided with conservative treatment in the two patients with a stoma, but seven patients without a stoma developed peritonitis requiring laparotomy. No deaths resulted from leakage, and there was one hospital death (0.6%) in the whole group. Median hospital stay was similar with and without a stoma (13.0 vs. 12.0 days) (p = 0.290). Closure of the stoma was associated with no mortality, a morbidity rate of 8.7%, and a median hospital stay of 6. 0 days. In conclusion, a defunctioning stoma is effective in preventing clinical anastomotic leakage after low anterior resection with total mesorectal excision. The relatively high incidence of leakage in the low risk group indicates the difficulty of predicting anastomotic leakage and hence the need for more liberal use of a defunctioning stoma especially in male patients.

Adult↗
PubMed1999

Modulation of reduction of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by vitamin C-palmitate.

An in vitro study of effects of vitamin C-palmitate on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in rat microsomes was performed. A sensitive assay method has been developed for the detection of metabolites of NNK in microsomes. Only the reduced metabolite of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL), was detected and measured in a time-course study. Vitamin C-palmitate enhanced the reduction of NNK in a concentration-dependent manner. The results indicate a significant increase in Vmax and K(m) in the presence of vitamin C. However, the rate of formation of NNAL at low substrate concentration varied. The ratio of Vmax to K(m) decreases. The results suggest that the kinetics are accounted for best by an uncompetitive activator binding model at low concentration of vitamin C. The uncompetitive binding model becomes sketchy at higher concentration of vitamin C. These observations infer that vitamin C loosely binds to the substrate-enzyme complex. Furthermore, the nature of the binding would facilitate the modulation of NNK biotransformation leading to the formation of NNAL. The results also show that vitamin C-palmitate is a potent activator of NNK reduction in rat liver microsomes. Thus, vitamin C-palmitate would mediate the metabolism of NNK through reduction. The resulting NNAL-glucuronide is more readily eliminated in urine.

Animals↗
PubMed1999

Phenotypic and cytotoxic characteristics of peripheral T-cell and NK-cell lymphomas in relation to Epstein-Barr virus association.

AIMS: We investigated the phenotypic and cytotoxic characteristics of different types of peripheral T-cell and NK-cell lymphomas and correlated the findings of cytotoxic phenotype with Epstein-Barr virus (EBV) association. METHODS AND RESULTS: Eighty cases of peripheral T-cell and NK-cell lymphomas, classified according to the REAL classification, were investigated for cytotoxic phenotype (by studying T-cell intracellular antigen-1 (TIA-1) expression immunohistochemically) and EBV association (by in situ hybridization for EBV-encoded small non-polyadenylated RNAs), and the results were correlated with the specific clinicopathological types and the immunophenotype with special emphasis on CD56 expression and CD4/CD8 status. Overall, 39/80 cases (49%) expressed TIA-1. Angiocentric lymphoma (23/24 cases; 96%), aggressive NK-cell leukaemia ('large granular lymphocyte (LGL) leukaemia') (3/3 cases; 100%), intestinal T-cell lymphoma (5/6 cases; 83%) and anaplastic large cell lymphoma (4/6 cases; 67%) were the major subtypes showing a cytotoxic phenotype. Only four of the 27 cases (15%) of peripheral T-cell lymphoma, unspecified, were TIA-1+, while all the seven cases of angioimmunoblastic T-cell lymphoma, six cases of mycosis fungoides and one case of adult T-cell lymphoma/leukaemia were TIA-1-. CONCLUSIONS: Within the group of peripheral T-cell and NK-cell lymphomas, angiocentric lymphoma, aggressive NK-cell leukaemia ('LGL leukaemia'), intestinal T-cell lymphoma and anaplastic large cell lymphoma are the major subtypes displaying a cytotoxic phenotype. The relationships between the cytotoxic phenotype and EBV association, CD56 expression or CD4/CD8 status are secondary to the relationship between cytotoxic phenotype and specific lymphoma subtype.

Adult↗