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Biomedical subjects

M Partridge

Publications and source records attributed to M Partridge.

At least 73 records · Page 4Linked to original sources
PubMed1996

A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.

Adult↗
PubMed1996

LOH at 3p correlates with a poor survival in oral squamous cell carcinoma.

We analysed chromosome 3p for loss of heterozygosity (LOH) in 48 primary oral squamous cell carcinomas (SCCs) using 15 markers and constructed a deletion map for this chromosome arm. LOH at one or more loci was found in 34/48 (71%) of tumours. The data support the existence of at least three distinct regions of deletion at 3p24-26, 3p21.3-22.1 and 3p12.1-14.2. A significant correlation was observed between the number of regions showing allele loss at 3p and tumour stage, consistent with the progressive accumulation of genetic errors during the development of oral SCC. There were also significant associations between LOH at 3p and disease-free and overall survival of patients with early stage disease. This study is the first to demonstrate the prognostic significance of LOH at 3p for oral cancer and may help to identify patients who should receive more aggressive treatment.

Adult↗
PubMed1996

A simple method for delivering morpholino antisense oligos into the cytoplasm of cells.

We report a simple and effective means for delivering Morpholino antisense oligos into the cytosol of cultured anchorage-dependent animal cells. This method, referred to as scrape-loading, is carried out in a matter of seconds, uses a common inexpensive laboratory implement, and has minimal detrimental impact on the cells. Using this delivery method, a Morpholino oligo present at 0.1 microM and 1 microM in the extracellular medium inhibited its targeted genetic sequence within cultured Hela cells at levels of 56% and 85%, respectively. Lack of inhibition by two control Morpholino oligos at concentrations up to 3 microM indicates good sequence specificity by this structural type. Also described is a test system for simple, rapid, and sensitive quantitation of antisense activity in cultured cells.

Animals↗
PubMed1996

Expression of TNF and the 55-kDa TNF receptor in epidermis, oral mucosa, lichen planus and squamous cell carcinoma.

UNLABELLED: TNF has diverse biological effects including a role in the immune response and growth regulatory effects. OBJECTIVES: The aim of this study was to determine the nature and location of cells able to synthesise and respond to TNF in oral mucosa in health and disease. MATERIALS AND METHODS: The location of immunoreactive TNF and 55-kDa and 75-kDa TNF receptors was demonstrated using immunohistology. We also used RT-PCR to help determine the sites of synthesis of this cytokine in oral mucosa. RESULTS: Only occasional TNF-positive cells were detected in normal epidermis and oral mucosa. However, this cytokine was found throughout the epithelia in oral lichen planus, leukoplakia and squamous cell carcinoma (SCC). The possible cellular sources and biological effects of TNF in these disease processes is discussed. The 55-kDa TNFR was expressed at the cell membrane throughout the epidermis, but confined to the lower cell layers on oral mucosa. Ten of 22 SCC did not express this receptor. A significant correlation was observed between the velocity of tumour growth and absence of TNF receptors. CONCLUSIONS: The growth inhibitory and immunoregulatory effects of TNF may be modulated by changes in receptor expression and alterations in synthesis of this cytokine in a subgroup of oral SCC.

Carcinoma, Squamous Cell↗
PubMed1994

Frequent deletion of chromosome 3p in oral squamous cell carcinoma.

Evidence suggests that the accumulation of genetic lesions in dominant oncogenes and tumour suppressor genes is involved in the development of human cancers. We have used restriction fragment length polymorphism analysis to identify chromosomal deletions which may indicate the location of potential tumour suppressor genes. Deletion of chromosome 3p was found in 17/21 (81%) of informative primary oral squamous cell carcinoma (SCC) using a polymorphic probe recognising the D3F15S2 locus (3p21). Loss of heterozygosity (LOH) was not confined to patients exposed to recognised risk factors such as heavy smoking or alcohol consumption and was present at an early stage in the disease suggesting that this genetic alteration may be a fundamental event for oral cancer.

Adult↗
PubMed1992

Expression of the tumour suppressor gene p53 in oral cancer.

In this preliminary series, the product of the tumour suppressor gene p53 was detected in 12/15 cases of oral squamous cell carcinoma (SCC) and in two cases of leukoplakia. The tumours either expressed the mutant form of p53 throughout the specimen or contained focal areas of positive cells. p53 expression was commonly observed in tumours obtained from patients who were heavy smokers and drinkers suggesting that alterations in the p53 gene may be one of the sites of genetic damage in this group of patients.

Alcohol Drinking↗
PubMed1991

Production of interleukin-1 and interleukin-6 by human keratinocytes and squamous cell carcinoma cell lines.

Cultured human keratinocytes and squamous cell carcinoma (SCC) cell lines were analyzed for the presence of ribonucleic acid (RNA) transcripts for the cytokines interleukin-1 and interleukin-6 and for these proteins. This study demonstrates that both cytokines are synthesized and secreted by both normal keratinocytes and SCC lines. The rate of secretion of these cytokines can be augmented in response to a variety of stimuli including tumor necrosis factor-alpha, granulocyte-macrophage colony stimulating factor, transforming growth factor-beta and the combination of lipopolysaccharide and phorbol myristate acetate. Interleukin-1 and interleukin-6 have been reported to influence the proliferation of cultured human fibroblasts. However, these cytokines had no significant effect on the proliferation of human keratinocytes or the SCC lines tested. Although it seems unlikely that interleukin-1 or interleukin-6 could directly influence keratinocyte proliferation in vivo, the capacity of these cells to synthesize and release these cytokines supports earlier observations that keratinocytes may play an important role in augmenting an immune or inflammatory response.

Carcinoma, Squamous Cell↗
PubMed1989

Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.

A total of 610 patients with small cell lung cancer were entered into a randomised trial designed to assess the effect of duration of initial chemotherapy on survival. Patients were randomised to receive either four or eight courses of cytotoxic chemotherapy with cyclophosphamide, vincristine and etoposide and also randomised to receive, on disease progression, either second line chemotherapy (methotrexate and doxorubicin) or symptomatic treatment only. In the whole study 196 (32.1%) had limited disease and 414 (67.9%) extensive disease. During initial chemotherapy the response rate (complete and partial responses) after four courses of treatment was 61% with no significant increase in patients receiving eight courses (63%). In those randomised to receive relapse chemotherapy the response rate was improved slightly for those who had originally received four courses of chemotherapy (25.6%) over those receiving eight (18.7%). The overall results show that of the four possible treatment randomizations, four courses of chemotherapy alone is inferior in terms of overall survival (30 weeks median survival) to the other three treatment options (39 weeks median survival, P less than 0.01). In patients responding to initial chemotherapy the disadvantage of four courses of chemotherapy alone was apparent (median survival of 40 weeks versus 49 weeks, P = 0.003) but not if drug treatment was given on relapse. The study shows that limiting treatment to four courses of chemotherapy alone is associated with inferior survival, but this is not the case if chemotherapy is given at relapse.

Adult↗
PubMed1989

Production of TGF-alpha and TGF-beta by cultured keratinocytes, skin and oral squamous cell carcinomas--potential autocrine regulation of normal and malignant epithelial cell proliferation.

Transforming growth factors have a wide range of biological activities related to cell proliferation and differentiation. In general TGF-alpha promotes cell proliferation while TGF-beta may stimulate or inhibit proliferation depending on the cell type and growth factor environment. Cultured human keratinocytes, skin and oral squamous cell carcinomas were analysed for the presence of transcripts and protein for the transforming growth factors alpha & beta. Both growth factors were detected in cultured keratinocytes (which have receptors for and respond to both ligands), and in medium conditioned by these cells. Additionally transcripts for TGF-alpha were found preferentially in the basal, proliferative compartment of cultured keratinocytes. Similarly both growth factors were detected in oral squamous cell carcinomas and a highly significant inverse correlation was found between the levels of TGF-alpha and the epidermal growth factor receptor in these tumours. The data for TGF-alpha are consistent with the existence of an autocrine growth control loop influencing cell proliferation in both a normal cell type and malignant epithelial tissues, a process that in keratinocytes and responsive squamous cell carcinomas could be modulated by TGF-beta.

Carcinoma, Squamous Cell↗
PubMed1988

Review of hepatitis non-A, non-B: the potential hazards in dental care.

Several of the common viral agents that can cause hepatitis have been detected in body fluids, including saliva and blood, which may both form important routes for transmission of disease. The viruses most commonly implicated include hepatitis A virus (HAV), hepatitis B virus (HBV), cytomegalovirus (CMV), and Epstein-Barr virus. Hepatitis delta virus (HDV) can be found in persons positive for hepatitis B surface antigen (HBsAg) and presumably follows the same routes of transmission as HBV. Herpes simplex and echo viruses can cause hepatitis on rare occasion. Other agents, not yet positively identified but collectively referred to as non-A, non-B are also believed to follow the same routes as HBV and/or HAV. The aim of this reviews is twofold. First, we will discuss hepatotropic viruses other than HBV that may be spread via saliva and blood and, therefore, should be considered along with HBV as a potential health hazard to dental personnel and also to dental patients. The second aim is to highlight the epidemiology and the risk of transmission of these viral infections. The potential hazards are discussed in relation to those associated with HBV and human immunodeficiency viruses (HIV), implicated in the acquired immunodeficiency syndrome (AIDS).

Dental Care for Persons with Disabilities↗
PubMed1988

Expression of epidermal growth factor receptor on oral squamous cell carcinoma.

The expression of the receptor for epidermal growth factor (EGF) in normal oral mucosa, papillomas and squamous cell carcinoma (SCC) has been determined by immunohistology and autophophorylation studies. Immunoreactive receptor was localised using two antibodies which recognise the receptor; EGFR1 which reacts with sequences in the external domain of the receptor and F4 which recognises sequences in the internal domain. EGFR was present on basal, suprabasal and some spinous cells of normal oral mucosa. Regional variation in the distribution of receptor was apparent. A similar pattern of receptor expression was seen on oral papillomas. The distribution and intensity of epidermal growth factor receptor (EGFR) expression varied between 20 patients with oral SCC. The staining patterns seen with the two antibodies were similar on all tissue types. The protein tyrosine-kinase activity of the receptor present on eight oral SCC was also examined by immunoprecipitation and autophosphorylation studies. This procedure also demonstrated variations in the amount of functional EGFR in these tumours. There was no significant correlation between the level of EGFR expression and tumour behaviour.

Carcinoma, Squamous Cell↗
PubMed1987

Review of the herpesviruses and hepatitis A: the potential hazards in dental care.

There is now an increased awareness of the risk of transmission of viral infections via blood and saliva after the publicity given to the human immunodeficiency viruses responsible for the acquired immunodeficiency syndrome. The herpesviruses have been found in blood, in blood products, and in saliva, and information with respect to these routes of transmission is convincing. Although hepatitis A virus is spread predominantly by water contaminated with feces (fecal-oral route), the virus is also found in saliva. On these grounds alone, these viruses must be considered a potential hazard in dentistry. Information in regard to the actual risks of their transmission in the context of dental practice is not yet available, primarily because a high proportion of infections are asymptomatic. Serologic studies of their prevalence suggest that all are widespread in the population. They are particularly common in many of the groups known to be at high risk for hepatitis B virus and human immunodeficiency virus, including promiscuous homosexuals, bisexuals, and intravenous drug abusers. In addition, pregnant women and their babies are particularly at risk from the herpesviruses. It is important to identify members of these high-risk groups as a potential source of transmission of infection through dental practice and in addition, it is important to identify them because they are prone to chronic sequelae.

Dental Care for Persons with Disabilities↗
PubMed1987

The primordial cyst (odontogenic keratocyst): its tumour-like characteristics and behaviour.

The clinical behaviour of primordial cysts frequently mimics that of benign tumours. They are characterised by aggressive growth and a tendency to recur following surgical treatment. Displacement of teeth, resorption of the roots of teeth, 'seeding' of the cyst into soft tissue and pathological fracture of the mandible exemplify this behaviour. These features are described and fully illustrated by examples from a series of 60 cases. The results of various surgical procedures are evaluated.

Adolescent↗