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J K Field

Publications and source records attributed to J K Field.

At least 19 recordsLinked to original sources
PubMed1995

Loss of heterozygosity at 9p23 defines a novel locus in non-small cell lung cancer.

Genetic studies have previously demonstrated cytogenetic deletions and allelic imbalance or loss of heterozygosity (LOH) on the p arm of chromosome 9, in a number of tumour types. We have analysed 45 Non-Small Cell Lung Cancers (NSCLC) with a panel of highly polymorphic microsatellite markers on chromosome 9. Our results indicate that loss on 9p is concentrated within the D9S156-D9S161 region with 44% (20/45) LOH, however the area with minimal loss in this set of lung tumours was found at D9S157 (9p23), with 30% LOH (10/33), whereas loss at the IFNA locus was only found in 6% (2/34) tumours. Five of the lung tumours in this study which demonstrated LOH at D9S157 retained heterozygosity at the adjacent informative markers lying centromeric and telomeric to D9S157. No correlations were found between any of the clinico-pathological parameters and LOH on 9p or at the D9S157 locus. The results of this study indicates the presence of a further putative tumour suppressor gene on 9p at the D9S157 locus (9p23) to be most likely involved in the pathogenesis of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

The treatment of node negative squamous cell carcinoma of the postcricoid region.

This study includes 155 patients with T1-4N0 carcinoma of the postcricoid region seen between 1963 and 1993. Sixty-seven were treated by primary surgery, 50 by primary irradiation therapy, 36 were unsuitable for curative treatment and two patients were lost to follow-up. Reasons for deciding against curative therapy were: advanced age, poor general condition and advanced disease at the primary site. This study included only those patients who had no neck node metastases at presentation. Patients receiving surgery tended to be in better general physical condition and tended to have more advanced disease than those treated by irradiation in this series. The tumour-specific five-year survival rate for those treated by surgery was 43 percent (95 percent confidence interval (CI) 23-60 percent). For those patients treated by irradiation the five-year survival rate was 48 percent (95 percent CI 27-66 percent) and for those receiving no treatment the median survival rate was three months (95 percent CI two-six months). The observed survival for the surgery group was only 18 percent and for the radiotherapy group 25 percent at five years. Multiple logistic regression showed no significant difference in proportions of host and tumour factors between the group receiving radiotherapy and the group receiving surgery. Recurrence at the primary site and the appearance of neck node metastases were not predicted by any host or tumour factor. Twenty-one patients out of 67 receiving primary surgery had recurrence at the primary site compared with 26 patients out of 50 receiving primary irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Frequent loss of heterozygosity on chromosome 17 at 17q11.2-q12 in Barrett's adenocarcinoma.

Allelic loss on chromosome 17 in 18 Barrett's oesophageal tumours was analysed with 17 polymorphic microsatellite markers. Loss of heterozygosity (LOH) of one or more markers was seen in 72% (13 of 18) tumours on 17p and 56% (10 of 18) on 17q. The highest 17p losses were found at D17S799 (62%, five of eight) and D17S261 (55%, five of nine), while loss at the p53 locus was 31% (5 of 16). The highest loss on 17q was found at the TCF-2 (17q11.2-q12) locus with 66% (8 of 12) LOH. TCF-2 was the only marker lost in two of the tumour samples; furthermore, TCF-2 was lost in four other tumours which retained heterozygosity at the markers on either side of it, D17S261 and D17S740. Six markers were used to assess LOH at 17q11.2-q12, and five of eight of the tumour specimens which had LOH at TCF-2 had no other loss on 17q. No statistically significant correlations were found between loss on 17q or 17p and any clinicopathological parameters. We propose from these data that the 17q11.2-q12 region contains a novel predisposing gene in Barrett's adenocarcinomas and may represent the site of a tumour-suppressor gene.

Adenocarcinoma↗
PubMed1995

Microsatellite instability in squamous cell carcinoma of the head and neck.

Genomic instability or microsatellite instability (MI) in simple repeated sequences was initially recognised in colonic carcinomas and subsequently in other tumours. MI has been associated with mutations in genes concerned with replication and DNA repair. We investigated 34 microsatellite markers in squamous cell carcinoma of the head and neck (SCCHN). Fifty-six tumours, were studied, of which 25 were investigated with ten or more microsatellite markers. In this study we consider two or more microsatellite alterations in a tumour to be diagnostic of MI. We demonstrated that 7/25 (28%) of the tumours had MI at two or more loci and three of these tumours exhibited evidence of 20 or more loci with MI. No correlations were found between MI and previous treatment, site, histological differentiation, positive nodes at pathology, a history of alcohol intake or survival. MI has been demonstrated in T1N0 stage tumours, indicating that these changes may occur early in the disease process. A negative correlation was found between MI and a history of smoking (P = 0.02). Two or more markers of MI were found in three of four non-smokers compared with one of 13 in the smoking group of patients, which suggests a novel mechanism of carcinogenesis in non-smokers.

Carcinoma, Squamous Cell↗
PubMed1995

Mutations, expression and genomic instability of the H-ras proto-oncogene in squamous cell carcinomas of the head and neck.

Mutation and overexpression are the main activating mechanisms for the ras family of genes in human cancer and the variable tandem repeat (VTR) located at the 3' end of H-ras has been associated with this risk. In the present study, we have analysed the relative levels of expression of H-ras mRNA in 26 samples of squamous cell carcinomas of the head and neck (SCCHN) by competitive reverse transcription-polymerase chain reaction (competitive RT-PCR) and also investigated whether there is an association between ras expression and alterations in the 3'-VTR region. In addition, we have studied the incidence of point mutations in codon 12 of H-ras, codons 12 and 13 of K-ras and codon 61 of N-ras in 120 SCCHN samples. Our results indicate that only two samples carry mutations, both of which are located in codon 12 of K-ras, but that overexpression of the H-ras proto-oncogene is a frequent event in SCCHN [54% (14/26)] and is associated with a favourable prognosis: 3 of 14 patients with H-ras overexpression have died, whereas 9 of 12 patients with low levels of H-ras expression have died. We have also undertaken an analysis of these results together with our previous investigations on microsatellite instability and loss of heterozygosity in SCCHN, but no associations were found. We therefore conclude that ras mutations are an infrequent event in the progression of the SCCHN in the Western world, whereas overexpression of the H-ras proto-oncogene is a common event.

Base Sequence↗
PubMed1995

Allelotype of squamous cell carcinoma of the head and neck: fractional allele loss correlates with survival.

Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour-suppressor genes. We have undertaken an extensive allelotype of 80 specimens of squamous cell carcinoma of the head and neck (SCCHN) using 145 polymorphic microsatellite markers on 39 chromosome arms. Allelic imbalances were found most frequently on chromosome arms 3p, 9p, 17p and 18q with over 45% LOH and imbalances on 1p, 1q, 2p, 5q, 6p, 6q, 8p, 8q, 9q, 11q, 13q, 17q and 19q were found in more than 20% of SCCHN. These LOH data were analysed against a range of clinicopathological parameters which included previously untreated and previously treated tumours; correlations were found between LOH on 9q and nodes at pathology (P = 0.02) and between histopathological grade and LOH on 12q (P = 0.02) and 13q (P = 0.01). In the group of previously untreated tumours, a correlation was found between site of tumour and LOH on 3p (P = 0.019), and 8p (P = 0.029), while TNM staging correlated with LOH on 3p (P = 0.019) and 17p (P = 0.016). Fractional allele loss (FAL) was calculated for 52 tumours with LOH data on nine or more chromosomal arms and found to have a median value of 0.22 (range 0.0-0.80). Correlations were found between FAL > median value and nodes at pathology (P = 0.01) and tumour grade (P = 0.06), demonstrating that advanced tumours with lymph node metastasis often had LOH at multiple sites. FAL > median value was found to correlate with a poor survival (P < 0.03) and, furthermore, FAL > median value correlated with poor survival in the previously untreated patients (P < 0.019). These results indicate that assessment of the accumulation of genetic damage, as provided by allelotype data, provides a useful molecular indicator of the tumour behaviour and clinical outcome.

Alleles↗
PubMed1995

Chromosome 18: a possible site for a tumour suppressor gene deletion in squamous cell carcinoma of the head and neck.

The present study analyses tumour samples from 41 patients with squamous cell carcinoma of the head and neck (SCCHN) using the polymerase chain reaction (PCR) to detect genetic alterations on chromosome 18. Microsatellite markers were used to examine each sample for loss of heterozygosity (LOH) and microsatellite instability. Genetic alterations were most commonly noted on the long arm of chromosome 18 (18q). LOH/microsatellite instability occurred on 18q in 20/41 (49%) of patients. The highest single incidence of LOH was found at 18q21.1-21.3 using the microsatellite marker D18S35. LOH occurred in 10/30 (33%) informative cases while LOH/microsatellite instability occurred in 13/30 (43%) informative cases using this marker. Interestingly the tumour suppressor gene known as the 'deleted in colonic carcinoma' (DCC) gene is located in this region at 18q21.3 but is not commonly lost. This suggests that the marker D18S35 is mapping close to a second as yet unidentified tumour suppressor gene in this area.

Adult↗
PubMed1992

Multiple cytogenetic aberrations in squamous cell carcinomas of the head and neck.

Chromosomal abnormalities in short term cultures have been investigated in 10 squamous cell carcinomas of the head and neck. Of these tumours, three demonstrated clonal chromosomal abnormalities, two showed random abnormalities and 5 patients' tumours had normal karyotypes. The 5 patients with aberrant karyotypes were all from previously treated tumours, of these, 4 patients had received radiotherapy and 1 surgery. On analysis of the three clonal tumours, two were found to be polyclonal, each with five separate clones. 116 breakpoints were demonstrated from the clonal data of these tumours, and all of the chromosomes were involved, apart from number 18. In this study we found three or more breakpoints at sites 1p36, 9q32 and 11q23. 1 of the patients investigated showed a clonal abnormality involving a breakpoint at the 11q13 site, with a further 2 patients having breakpoints at 1p22--sites previously reported to have marked clustering of cytogenetic abnormalities in oral cancer patients. Only further studies will demonstrate whether the breakpoints found are of clinical significance.

Carcinoma, Squamous Cell↗
PubMed1992

Oncogenes and tumour-suppressor genes in squamous cell carcinoma of the head and neck.

Cancer is now considered to be a multi-hit process which involves a number of aberrant genetic events culminating in malignant transformation. In squamous cell carcinoma (SCC) of the head and neck the action of both oncogenes and tumour-suppressor genes has been identified during the course of the disease. Cytogenetic analysis of these carcinomas has demonstrated chromosomal breakpoints, particularly in the regions of 1p22 and 11q13 together with frequent amplification of the proto-oncogenes in the 11q13 amplicon; int-2, hst-1 and bcl-1. Ras mutations have been infrequently identified in the Western World whereas ras over-expression has been a common finding and may be associated with the early development of head and neck cancer. C-myc over-expression appears to correlate with a poor prognosis for these patients. The tumour-suppressor gene p53 is also thought to be involved in the development of SCC in head and neck tumours and its aberrant expression is associated with a history of heavy smoking and heavy drinking. E-cadherin, a putative tumour-suppressor gene is down-regulated in poorly differentiated head and neck SCC and maybe important in nodal metastasis. A recent study has indicated that the Human Papilloma Virus (HPV 16 and 33) has a role in the aetiology of tonsillar carcinomas and HPV has been shown to produce transforming proteins which bind to and inactivate the p53 tumour suppressor gene. This evidence suggests that the possibility of a viral mechanism for the development of SCC in the head and neck should be considered. This paper proposes a series of genetic events to explain the development of SCC of the head and neck.

Cadherins↗
PubMed1992

A phase II study of cisplatinum versus cisplatinum + nifedipine in end-stage carcinoma of the head and neck.

Forty patients with end-stage carcinoma of the head and neck were admitted to a randomized double blind trial with cisplatinum in one arm and cisplatinum + nifedipine in the other. Nifedipine, a calcium channel blocking drug, inhibits the effect of acquired multidrug resistance in animal models. In the present study the addition of this agent had no effect on either response rate or survival in end-stage carcinoma of the head and neck. It is concluded that adding nifedipine to cisplatinum serves no useful purpose in the treatment of end-stage carcinoma of the head and neck.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Low levels of ras p21 oncogene expression correlates with clinical outcome in head and neck squamous cell carcinoma.

We have previously demonstrated that the Ha-ras and the Ki-ras oncogenes are overexpressed in squamous cell carcinoma of the head and neck. In this study we have used the Y13-259 monoclonal antibody to p21 ras to determine if expression of the ras oncoprotein correlates with any of the clinico-pathological parameters or with survival in 69 patients with squamous cell carcinoma of the head and neck. Forty-four specimens were from patients with previously untreated tumours and 25 from patients with previously treated disease. We have found a correlation between low levels of ras expression and the disease-free survival period in patients with previously untreated tumours. Three per cent of the patients with ras negative staining were alive 60 months after diagnosis, whereas 54 per cent of the patients with positive staining were still alive after the same time period (P less than 0.05).

Animals↗
PubMed1991

Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck.

Expression of the tumour suppressor gene p53 was examined in squamous cell carcinoma of the head and neck using two p53 antibodies, PAb 421 and PAb 1801. Elevated p53 expression was found in 67% of the 73 patients investigated. P53 expression was not found to correlate with whether the patient had been previously treated or not, nor any of the clinico-pathological parameters. However a correlation was found between the patients smoking history and positive p53 staining. Six out of seven non-smokers did not express p53 whereas 29 of 37 heavy smokers were found to have elevated p53 expression (P less than 0.005). Also, of a group of ten patients who had given up smoking more than 5 years ago, nine had elevated expression. Epidemiological studies have shown a correlation between heavy smoking and head and neck cancer. The present study indicate a genetic link for this correlation.

Carcinoma, Squamous Cell↗
PubMed1991

Immunohistochemical analysis of the expression of the c-myc oncoprotein in human stomach cancers.

In an immunohistopathological study, we have used the specific monoclonal antibody myc 1-9E10 to the c-myc oncoprotein in 88 gastric carcinomas (22 gastric biopsies and 66 gastrectomies for cancer). Positive myc p62 immunoreactivity was shown in 48 (55%) cases with moderate or intense staining. The remaining 40 cases exhibited negative or equivocal staining. Normal stomach mucosa was generally nonreactive, with the exception of parietal cells. Elevated c-myc expression was not found to correlate with histological differentiation or in patients with metastases in one or more perigastric lymph nodes. A correlation was found between the level of c-myc expression and the stage of the disease, (p = 0.04); positive c-myc staining was found in 0/4 early gastric cancers and in 48/84 with advanced disease. Also, an association was found between the elevated c-myc expression and depth of invasion (p = 0.1; 0/4 mucosa and submucosa, 2/6 muscularis propria and 25/47 serosa). The c-myc monoclonal myc 1-9E10 may therefore be of use as a marker of advanced disease and depth of invasion in stomach cancer.

Adenocarcinoma↗
PubMed1989

Elevated expression of the c-myc oncoprotein correlates with poor prognosis in head and neck squamous cell carcinoma.

We quantitated c-myc oncoprotein in 44 squamous cell carcinomas of the head and neck using an enzyme-linked immunosorbence assay. The clinicopathological parameters of these patients were followed up for between 3 and 60 months and analysed for any correlations with observed levels of c-myc protein using the Kruskal-Wallis one-way analysis of variance method. Although no statistical correlation was found between different clinicopathological parameters (patient age, sex, TNM staging, number of lymph nodes invaded, extracapsular rupture of the tumour, its histopathological differentiation, or its site), the survival periods of patients with tumours possessing elevated levels of c-myc protein were found to be statistically shorter than those with lower levels of c-myc expression, (P less than 0.02). This indicates that c-myc expression may be an effective prognostic indicator in head and neck cancer.

Animals↗
PubMed1989

Does Candida have a role in oral epithelial neoplasia?

Candida species are responsible for a wide variety of superficial infections of man [59] and the pathogenic role of these yeasts in many conditions has now been defined. There is, however, a great deal of controversy concerning the role of Candida species in the development of epithelial neoplasia. Vaginal and cutaneous candidosis are relatively common but there is little firm clinical or epidemiological evidence to link them to cervical neoplasia or skin carcinoma [59]. The converse is true however for oral candidosis where chronic Candida infection and neoplasia have been strongly linked. The aim of this review is to explore and evaluate the experimental and epidemiological evidence supporting an association between Candida species and oral neoplasia.

Animals↗