PubMed Health⌕ Search

Biomedical subjects

H Rigby

Publications and source records attributed to H Rigby.

13 recordsLinked to original sources
PubMed2006

Chemokine-mediated migration of melanoma cells towards lymphatics--a mechanism contributing to metastasis.

The mechanisms that cause tumors such as melanomas to metastasize into peripheral lymphatic capillaries are poorly defined. Non-mutually-exclusive mechanisms are lymphatic endothelial cell (LEC) chemotaxis and proliferation in response to tumor cells (chemotaxis-lymphangiogenesis hypothesis) or LECs may secrete chemotactic agents that attract cancer cells (chemotactic metastasis hypothesis). Using migration assays, we found evidence supporting both hypotheses. Conditioned medium (CM) from metastatic malignant melanoma (MMM) cell lines attracted LEC migration, consistent with the lymphangiogenesis hypothesis. Conversely, CM from mixed endothelial cells or LECs, but not blood endothelial cells, attracted MMM cells but not non-metastatic melanoma cells, consistent with the chemotactic metastasis hypothesis. MMM cell lines expressed CCR7 receptors for the lymphatic chemokine CCL21 and CCL21 neutralizing antibodies prevented MMM chemotaxis in vitro. To test for chemotactic metastasis in vivo tumor cells were xenotransplanted into nude mice approximately 1 cm from an injected LEC depot. Two different MMM grew directionally towards the LECs, whereas non-metastatic melanomas did not. These observations support the hypothesis that MMM cells grow towards regions of high LEC density owing to chemotactic LEC secretions, including CCL21. This chemotactic metastasis may contribute to the close association between metastasizing tumor cells and peri-tumor lymphatic density and promote lymphatic invasion.

Animals↗
PubMed2004

Lymphatic density and metastatic spread in human malignant melanoma.

Malignant melanoma (MM), the most common cause of skin cancer deaths, metastasises to regional lymph nodes. In animal models of other cancers, lymphatic growth is associated with metastasis. To assess if lymphatic density (LD) was increased in human MM, and its association with metastasis, we measured LD inside and around archival MM samples (MM, n=21), and compared them with normal dermis (n=11), basal cell carcinoma (BCC, n=6) and Merkel cell carcinoma (MCC), a skin tumour thought to metastasise through a vascular route (MCC, n=6). Lymphatic capillary density (mm(-2)), as determined by immunohistochemical staining with the lymphatic specific marker LYVE-1, was significantly increased around MM (10.0+/-2.5 mm(-2)) compared with normal dermis (2.4+/-0.9 mm(-2)), BCC (3.0+/-0.9 mm(-2)) and MCC (2.4+/-1.4 mm(-2)) (P<0.0001). There was a small decrease in LD inside MM (1.1+/-0.7 mm(-2)) compared with normal dermis, but a highly significant decrease in BCC (0.14+/-0.13) and MCC (0.12+/-2.4) (P<0.01 Kruskal-Wallis). Astonishingly, LD discriminated between melanomas that subsequently metastasised (12.8+/-1.6 mm(-2)) and those that did not (5.4+/-1.1 mm(-2), P<0.01, Mann-Whitney). Lymphatic invasion by tumour cells was seen mainly in MM that metastasised (70% compared with 12% not metastasising, P<0.05 Fisher's Exact test). The results show that LD was increased around MMs, and that LD and tumour cell invasion of lymphatics may help to predict metastasis. To this end, a prognostic index was calculated using LD, lymphatic invasion and thickness that clearly discriminated metastatic from nonmetastatic tumours.

Basal Cell Carcinoma↗
PubMed2003

The detection of tyrosinase mRNA in peripheral blood samples is unlikely to aid in the management of patients with localised malignant melanoma.

A number of authors have reported the detection of tyrosinase mRNA in the peripheral blood of patients with malignant melanoma using the reverse transcription polymerase chain reaction (RT-PCR). The precise value of this assay as a prognostic tool, however, remains in doubt. This is particularly so with relation to localised disease, where relatively little data has been accumulated. In this study we analysed the peripheral blood of 50 consecutive patients with primary malignant melanoma referred to a plastic surgical centre with the facility of a pigmented lesion clinic. Samples were analysed from an additional 35 patients with advanced melanoma disease and 35 patients with benign pigmented cutaneous lesions. We were able to identify tyrosinase transcripts in the peripheral blood of only two of 50 patients with localised disease. Of those with more advanced disease, a positive finding was found in three with regional disease and four patients with metastatic spread. Stage of disease was found to correlate significantly with PCR status. No correlation was identified with other prognostic markers or with outcome over a three-year period. This data would support the conclusion that the detection of tyrosinase mRNA in peripheral blood is likely to be of little value as an aid in the management of patients with early malignant melanoma.

Biomarkers, Tumor↗
PubMed2002

Detection of melanoma seeding during surgical procedures--an RT-PCR based model.

AIM: It has long been suggested that malignant cells may be shed into the blood stream during any given surgical procedure for cancer. A number of studies have now reported the detection of occult melanoma cells in peripheral blood using a reverse transcriptase polymerase chain reaction (RT-PCR) based assay. The principal aim of these studies has been to determine a prognostic value for the test and not to evaluate the influence of intervention upon results. METHODS: In this pilot study we aimed to determine whether the assay could be used as a model to detect cells that are seeded during surgery. Peripheral blood samples were obtained pre- and post-operatively on twenty patients undergoing surgery for malignant melanoma - ten with primary disease and ten undergoing regional lymphadenectomy. A further ten patients undergoing surgery for non-melanoma conditions provided controls. RESULTS: Using RT-PCR, it was possible to identify tyrosinase transcripts in the peripheral blood of one of ten patients undergoing excision of local disease and four of ten undergoing surgery for regional metastatic disease. CONCLUSION: It was concluded that this technique does enable detection of a greater percentage of RT-PCR findings post-operatively. This in turn may provide a means for optimizing or comparing surgical techniques and provides a potential guide in the use of adjuvant therapies.

Base Sequence↗
PubMed1997

Follow-up requirements for thick cutaneous melanoma.

The primary aim of postoperative melanoma follow-up is the early detection and treatment of treatable recurrences which gives a survival advantage to these patients. The need for follow-up is universally accepted. However, there is ongoing controversy about the duration of follow-up and frequency of reviews. We present a retrospective review of 244 patients with localised thick (> or = 4.0 mm) cutaneous melanoma, who had completed a 10-year follow-up or had died form their melanoma within 10 years. For these criteria, this is the largest series of this type which has been reported to date. The incidence of treatable recurrences peaked in the first postoperative year at 40% and then rapidly decreased, levelling off after year 5 at 2.5% per annum. We believe that this high incidence of treatable recurrences reinforces the need for 10-year follow-up of these patients. We also recommend that the annual frequency of follow-up reviews in each year be based on that year's risk for getting a treatable recurrence. Following this principle, we provide an example of such a follow-up programme.

Adult↗
PubMed1996

Allelotypes of primary cutaneous melanoma and benign melanocytic nevi.

A multistep genetic model of tumorigenesis, based on genetic alterations in benign and primary malignant lesions, has been proposed for neoplasms such as colonic carcinoma. However, evidence for a similar genetic progression in melanoma has relied heavily on findings in cultured lesions or metastases. We have investigated every autosomal arm for loss of heterozygosity in 41 primary cutaneous melanomas and 32 benign melanocytic nevi, and have investigated several chromosome arms that show loss in melanoma in 27 Spitz nevi (a nevus with histological similarities to melanoma). Loss of heterozygosity in primary melanoma was identified most frequently on chromosomes 9p (46%) at loci near the p16INK4 gene, 10q (31%), 6q (31%), and 18q (22%); loss of these chromosome arms were related to the progression of the melanoma. Only two benign melanocytic nevi (both of which showed atypical features on histology) demonstrated genetic alterations, including p9 loss in one case. In addition, two Spitz nevi contained interstitial deletions on chromosome 9p. Our findings show that loss of heterozygosity of 9p is not confined to melanoma, but that other uncultured melanocytic lesions can also display loss of this chromosome arm, and that other genetic changes (e.g., loss of 10q, 6q, and 18q) may be important in conveying the malignant phenotype to melanoma.

Alleles↗
PubMed1996

Perceptions of baby talk, frequency of receiving baby talk, and self-esteem among community and nursing home residents.

Community-living seniors (n = 113) and nursing home residents (n = 43) provided their impressions of baby-talk and neutral-talk scenarios and completed measures of functional health, need for succorance, and self-esteem. Two orthogonal dimensions were found in perceptions of baby talk: Warmth and Superiority. The personality trait of need for succorance was consistently associated with perceptions of warmth in baby talk, whereas functional health, age, and institutionalization were associated with perceptions of superiority. Significant interactions were found between perceptions of baby talk and frequency of receiving baby talk in the prediction of self-esteem, providing suggestive evidence for previously expressed concerns about potentially harmful effects of receiving baby talk on self-esteem among seniors who have negative perceptions of baby talk. However, older persons with positive perceptions of baby talk reported higher self-esteem when they frequently received baby talk, in accordance with person-environment theory. The self-esteem interaction for men occurred on the Superiority dimension, whereas the interaction for women occurred on the Warmth dimension.

Activities of Daily Living↗
PubMed1992

Rectal endosonography accurately predicts depth of penetration in rectal cancer.

Sixty-three patients with primary rectal adenocarcinomas have been examined prior to surgery with rectal endosonography (ES). Maximum depths of tumour penetration measured endosonographically have been compared with subsequent maximum depths measured on the fixed resected specimen (n = 30) and the histological slide (n = 61). In both cases there was a good degree of correlation between the ultrasonic estimations of depth and the histological ones (r = 0.36, p = 0.05, CI = 95% and r = 0.46, p less than 0.001, CI = 99% respectively). In 12 cases ultrasonic depths of tumour were also measured in the laboratory and then compared with depths from fixed (n = 12) and fresh specimens (n = 5) with a good correlation (r = 0.75, p = 0.005, CI = 99% and r = 0.79, p = 0.036, CI = 95% respectively). Rectal endosonographic estimation of rectal cancer depth of invasion is an accurate measure of tumour penetration and may help distinguish between fixation due to inflammatory tissue and tumour fixity.

Adenocarcinoma↗
PubMed1989

Preoperative assessment of mesorectal lymph node involvement in rectal cancer.

One hundred patients with rectal adenocarcinoma were examined preoperatively with rectal endosonography (ES) and 50 were also examined with computed tomography (CT). ES predicted mesorectal lymph node involvement with an accuracy of 83 per cent, sensitivity of 88 per cent, specificity of 79 per cent, positive predictive value of 78 per cent and negative predictive value of 89 per cent. CT in comparison had an accuracy of 57 per cent, sensitivity of 25 per cent, specificity of 91 per cent, positive predictive value of 75 per cent and negative predictive value of 53 per cent. No particular histological architectural feature could be identified as responsible for false positive diagnosis though nodal size was significantly larger in the true positive and false positive group when compared with the true negatives (P less than 0.001 and P less than 0.01 respectively).

Adenocarcinoma↗
PubMed1989

The detection and evaluation of locally recurrent rectal cancer with rectal endosonography.

Eighty-five patients treated surgically for rectal cancer have been followed up by conventional clinical examination, sigmoidoscopy, and endosonography. Local recurrence was diagnosed in 22 patients. Nineteen of these had either sigmoidoscopic or digital evidence of recurrence and three were diagnosed solely by endosonography. In all cases endosonography gave additional information on which to base management decisions. Routine use of endosonography should allow the detection of early recurrence in a larger number of patients.

Adult↗