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J Fitzgibbon

Publications and source records attributed to J Fitzgibbon.

At least 19 recordsLinked to original sources
PubMed2006

The activity of methylated and non-methylated selenium species in lymphoma cell lines and primary tumours.

BACKGROUND: Diffuse large B-cell lymphoma patients with low serum selenium concentration at presentation have a lower response rate and overall survival than patients with higher serum selenium. The co-administration of selenium with conventional chemotherapy may be useful in these patients. PATIENTS AND METHODS: We investigated the activity of two selenium species, methylseleninic acid (MSA) and selenodiglutathione (SDG) in a panel of human lymphoma cell lines and in a primary lymphoma culture system. RESULTS: Both compounds demonstrated cytostatic and cytotoxic activity with EC(50) values in the range 1.0-10.2 microM. Cell death was associated with an increase in the sub-G1 (apoptotic) fraction by flow cytometry and was not preceded by any obvious cell cycle arrest. SDG, but not MSA, resulted in marked increases in intracellular ROS, particularly in CRL2261 and SUD4 cells in which the cytotoxic activity of SDG was partly, or completely, inhibited by n-acetyl cysteine, suggesting a dependence on ROS for activity in some cells. Both MSA and SDG showed a concentration dependent reduction in percentage viability after a 2-day exposure in primary lymphoma cultures, with EC(50) values in the range 39-300 microM and 9-28 microM, respectively. CONCLUSION: The selenium compounds MSA and SDG induce cell death in lymphoma cell lines and primary lymphoma cultures, which with SDG may be partly attributable to the generation of ROS.

Apoptosis↗
PubMed2005

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target..

Cell Transformation, Neoplastic↗
PubMed2005

Paraesophageal lymph node metastasis from prostatic adenocarcinoma in a patient with esophageal squamous carcinoma.

SUMMARY. Esophageal squamous carcinomas induce regional immune suppression in the domain of the tumor while the global immune system remains intact. We report a patient with a squamous esophageal carcinoma, who was discovered at esophagectomy to have paraesophageal lymph node metastases from a prostatic adenocarcinoma. No other sites of metastatic disease were identified. This supports the concept that regional immune suppression by esophageal squamous cancers facilitates growth of metastases in the local lymph nodes.

Adenocarcinoma↗
PubMed2004

Efficacy and pitfalls of fine needle aspiration in the diagnosis of neck masses.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is now well established in the assessment of cervical masses. The purpose of the present study is to review the efficacy of this procedure, as well as to identify any pitfalls that may limit its usefulness. METHODS: One hundred and ninety aspirations of neck masses performed over a recent five-year period were reviewed. The definitive diagnosis of the mass was determined in each case by review of the patients' case notes. RESULTS: Thirty seven per cent of all neck lumps were malignant. The most common cause for a false-negative result, in the case of a carcinomatous mass when an adequate sample had been obtained, was a cystic neoplasm. One quarter of all cystic lateral cervical masses not considered suspicious for malignancy by FNAB turned out to be malignant. CONCLUSION: Repeating FNAB in cases where the original result is negative for carcinoma may increase the sensitivity of FNAB in the detection of cystic carcinomas.

Adenoma↗
PubMed2003

Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance.

BACKGROUND: Prophylactic efficacy against colitis following lactobacillus consumption in interleukin 10 (IL-10) knockout (KO) mice has been reported. Whether this applies equally to other probiotic strains is unknown, and the mechanism is unclear. AIMS: (1) To compare the effect of feeding Lactobacillus salivarius subspecies salivarius 433118 and Bifidobacterium infantis 35624 against placebo on enterocolitis, the intestinal microflora, and (2) to compare the systemic immunological response to in vitro microbial challenge in probiotic fed and control IL-10 KO mice. METHODS: Three groups of 10 IL-10 KO mice were fed fermented milk products containing Lb salivarius 433118 at 10(9) CFU/ml, B infantis 35624 at 10(8) CFU/ml, and unmodified milk, respectively, for 19 weeks. Faecal samples were taken at regular intervals to confirm gut transit, recovery of fed probiotics, and to assess the impact on the microflora. At sacrifice, the bowels were histologically scored. Cytokine production from Peyers' patches and splenocytes was measured in vitro by ELISA. RESULTS: Faecal recovery of probiotics was confirmed in all probiotic fed mice but not in controls. Colonic and caecal inflammatory scores were significantly decreased in both groups of probiotic fed mice (p<0.05). Proinflammatory cytokine production by Peyers' patches and splenocytes was significantly reduced in probiotic fed animals whereas transforming growth factor beta (TGF-beta) levels were maintained. CONCLUSION: Both Lactobacillus salivarius 433118 and Bifidobacterium infantis 35624 significantly attenuate colitis in this murine model. Attenuation of colitis is associated with a reduced ability to produce Th1-type cytokines systemically and mucosally, while levels of TGF-beta are maintained.

Animals↗
PubMed2002

Human herpesvirus 8 (HHV-8) detected in two patients with Kaposi's sarcoma-like pyogenic granuloma.

AIMS: To report the finding of human herpesvirus 8 (HHV-8) in two patients with Kaposi's sarcoma (KS)-like pyogenic granuloma. This form of pyogenic granuloma closely resembles KS histologically and it has been reported that immunohistochemistry in such lesions may be positive for smooth muscle actin and factor VIII related antigen, which are typically negative in KS. In both patients the lesions were positive for CD31, CD34, smooth muscle actin, and factor VIII related antigen, a profile typical of KS-like pyogenic granuloma. The lesions were tested for the presence of HHV-8 DNA, which to date has been consistently found in all types of KS. METHODS: The lesions were tested for the presence of HHV-8 DNA using the polymerase chain reaction (PCR). A known HHV-8 positive KS specimen was used as the positive control. Six samples of non-KS vascular skin lesions were used as negative controls for the PCR reaction. RESULTS: Both lesions were positive on PCR for HHV-8 and the specificity of product was confirmed by direct sequencing. None of the six control vascular skin lesions was positive for HHV-8. These results strongly indicate KS as the true diagnosis and are supported by the reported clinical course in both cases. CONCLUSIONS: Techniques targeting HHV-8 DNA for detection to confirm a diagnosis of KS are both sensitive and specific. In cases where the differential diagnosis includes KS-like pyogenic granuloma, caution should be taken not to diagnose solely on the basis of immunohistochemistry phenotype. In such cases, PCR targeting HHV-8 DNA sequences is a better diagnostic tool.

Aged↗
PubMed2001

Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma.

PURPOSE: To determine the incidence and frequency of the Bcl-2/IgH rearrangement in the peripheral blood of normal individuals to define the potential complication this may pose for the molecular monitoring of disease in patients with follicular lymphoma (FL). MATERIALS AND METHODS: The incidence and frequency of the major breakpoint cluster region rearrangement in DNA extracted from peripheral blood or lymphoblastoid cell lines from 481 normal individuals was determined using a TaqMan real-time polymerase chain reaction assay (PE Applied Biosystems, Foster City, CA). RESULTS: Twenty three percent of samples were positive for the Bcl-2/IgH rearrangement, with approximately 3% of these at levels of more than 1 in 10(4) cells. CONCLUSION: The presence of circulating Bcl-2/IgH+ cells, other than those derived from the malignant clone, could confound the detection and quantitation of minimal residual disease in patients with FL, particularly at low levels of tumor burden.

Adult↗
PubMed2001

Localisation of a novel region of recurrent amplification in follicular lymphoma to an approximately 6.8 Mb region of 13q32-33.

Follicular lymphoma (FL) is characterised by the presence of the t(14;18)(q32;q21) and represents approximately 25% of new cases of non-Hodgkin's lymphoma. While the t(14;18) is a well-documented rearrangement, the role of secondary cytogenetic abnormalities in the development and progression of these tumours remains unclear. Comparative genomic hybridisation was used to characterise changes in DNA copy number in tumour DNA from patients with this malignancy. The mean numbers of deletion and amplification events found in each of the 45 samples studied were 1.8 and 2.3, respectively. Regions of recurrent (>10% tumour samples) gain involved chromosomes 2p13-16 (16%), 7 (20%), 12 (16%), 13q21-33 (18%), 18 (27%), and X (36%) and frequent losses localised to 6q (29%) and 17p (20%). Amplification of chromosome 13 represents a novel finding in FL. The minimal amplified region was refined to a 6.8-Mb interval of 13q32-33 between the BAC clones 88K16 and 44H20 by fluorescence in situ hybridisation studies using metaphase chromosomes derived from tumour material. There are a number of reports in the literature suggesting that amplification of chromosome 13 also occurs in other human cancers. The location of the putative oncogene on 13q described here in follicular and transformed lymphoma may also be important in the evolution of many other malignancies.

Adult↗
PubMed2001

Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice.

BACKGROUND: The enteric bacterial flora has been implicated in the pathogenesis of enterocolitis and colon cancer in C57BL/6 IL-10 knockout mice. Probiotic Lactobacilli modify the enteric flora and are thought to have a beneficial effect on enterocolitis. We conducted a controlled feeding trial in IL-10 knockout mice using the probiotic Lactobacillus salivarius ssp. salivarius UCC118. AIM: To determine the effect of probiotic consumption on the gastrointestinal microflora, tumour development and colitis in IL-10 knockout mice. METHODS: Twenty IL-10 knockout mice were studied (10 consumed probiotic organisms in milk and 10 consumed unmodified milk) for 16 weeks. Faecal microbial analysis was performed weekly to enumerate excretion of the probiotic UCC118, total lactobacilli, Clostridium perfringens, bacteroides, coliforms, bifidobacteria and enterococci. At sacrifice, the small and large bowel were microbiologically and histologically assessed. RESULTS: L. salivarius UCC118 was detected in faeces from all mice in the probiotic fed group, but not the control group. Faecal coliform and enterococci levels were significantly reduced in probiotic fed animals compared to the controls (P < 0.05). At sacrifice, a significant reduction in C. perfringens numbers was observed in the test mice (P < 0.05). There were no fatalities in the test group compared to two deaths from fulminant colitis in the control group. Only one test mouse developed colonic adenocarcinoma compared to five in the control group. Test animal mucosal inflammation consistently scored lower than that of the control mice. CONCLUSION: In this placebo controlled trial, modification of enteric flora in IL-10 knockout mice by probiotic lactobacilli was associated with reduced prevalence of colon cancer and mucosal inflammatory activity.

Animals↗
PubMed2000

Neural fibrolipoma: an unusual case.

A 45-year-old gentleman presented with a diffuse left neck mass. Surgical exploration revealed a large lipomatous lesion. Histological examination identified this to be a neural fibrolipoma. This is the first reported case of this lesion in the neck.

Head and Neck Neoplasms↗
PubMed1999

Tumour necrosis factor polymorphisms and susceptibility to follicular lymphoma.

Follicular lymphoma is characterized in 85% of patients by the presence of a t(14;18) chromosomal translocation that results in overproduction of BCL2. In this study the distribution of high and low expressing TNF alleles at the TNF (-308) and LTalpha (+252) polymorphic sites in 121 patients with follicular lymphoma and 88 control individuals has been analysed. A reduction in high expressing haplotypes in patients compared to normal controls was found (P = 0.055), with no significant difference observed in response rate or overall survival between patients with high or low expressing haplotypes. These results suggest that the TNF locus, or an adjacent locus within the MHC region, is an important genetic risk factor in this disease.

Adult↗