Expression of angiogenic growth factors in laryngeal carcinoma.

Over 2,200 cases of carcinoma of the larynx are diagnosed in the UK annually, with an overall 5-year survival rate of 67%. Angiogenesis is vital for the growth and metastasis of solid tumours and the expression of key angiogenesis-related proteins has been shown to be of prognostic significance. In this study we reported the expression of key angiogenesis-related factors, selected from a pilot array study, in a cohort of laryngeal tumours and associated metastatic lymph nodes. Forty patients diagnosed with squamous cell carcinoma of the larynx were recruited. Tissue specimens were obtained intra-operatively, prior to chemo- and/or radiotherapy, from the tumours and secondary lymph nodes. The patient group comprised 32 men and 8 women with a mean age of 68 years (range, 51-89 years). The relative expression of the angiogenesis-related proteins angiogenin, interleukin (IL)-8, tissue inhibitor of metalloproteinases-1 (TIMP-1), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-basic and insulin-like growth factor binding protein 3 (IGFBP3) was determined in the tissue lysates by ELISA. The expression of angiogenin was higher in early-stage compared with late-stage tumours (P=0.034) and the expression of IGFBP3 was higher in tumours compared with the metastatic lymph nodes (P=0.016). No statistically significant differences were recorded for VEGF, FGF, TIMP-1 or IL-8 between tumour stages or primary tumours and lymph nodes. To the best of our knowledge, this study was the first to investigate multiple angiogenic factors in the lysates of laryngeal carcinomas and metastatic nodes and identified angiogenin and IGFBP3 as factors possibly involved in tumour progression. A greater understanding of their function may offer novel prognostic and/or therapeutic options.

Protein profiling of angiogenesis-related growth factors in laryngeal carcinoma: Pattern of protein expression in relation to tumour progression.

The expression of angiogenesis-related proteins was determined in laryngeal tumour tissue, associated tumour involved lymph nodes, apparently normal mucosa and control tissue and were related to tumour stage. Both laryngeal tumour tissue and associated metastatic nodes were obtained from seven patients undergoing surgical resection; in four cases apparently normal mucosa was also dissected from the tumour specimen margins. Control uvula mucosa was obtained from five healthy volunteers undergoing uvulopalatopharyngoplasty. The relative expression of 55 angiogenesis-related proteins was determined in tissue lysates using a Proteome Profiler human angiogenesis array kit. The level of 32/55 angiogenesis-related proteins was higher in tumour tissue compared with controls. Furthermore, in these tumour biopsies higher levels of proteins were associated with increasing tumour stage. A similar trend was seen for 29/32 of these proteins in the nodal tissue. In T4 stage tumour tissue samples, 29/55 angiogenensis-related proteins were more highly expressed compared with the adjacent normal mucosa from the same patient, and this decreased to 8 proteins in tumour tissue from the T1 stage patients. In contrast, the expression of 23 angiogenesis-related proteins in metastatic lymph node tissue from T4 stage patients was lower compared with that found in the normal mucosa adjacent to the tumour. In conclusion, this study has identified a number of factors involved in angiogenesis that are likely to contribute to the growth and metastasis of laryngeal tumours. Furthermore, a number of factors were also substantially altered in metastatic deposits compared with the primary tumour mass or adjacent normal tissue. This study requires confirmatory analysis of the selected key factors in a larger cohort of patients.

Genetic variation in South Indian castes: evidence from Y-chromosome, mitochondrial, and autosomal polymorphisms.

BACKGROUND: Major population movements, social structure, and caste endogamy have influenced the genetic structure of Indian populations. An understanding of these influences is increasingly important as gene mapping and case-control studies are initiated in South Indian populations. RESULTS: We report new data on 155 individuals from four Tamil caste populations of South India and perform comparative analyses with caste populations from the neighboring state of Andhra Pradesh. Genetic differentiation among Tamil castes is low (RST = 0.96% for 45 autosomal short tandem repeat (STR) markers), reflecting a largely common origin. Nonetheless, caste- and continent-specific patterns are evident. For 32 lineage-defining Y-chromosome SNPs, Tamil castes show higher affinity to Europeans than to eastern Asians, and genetic distance estimates to the Europeans are ordered by caste rank. For 32 lineage-defining mitochondrial SNPs and hypervariable sequence (HVS) 1, Tamil castes have higher affinity to eastern Asians than to Europeans. For 45 autosomal STRs, upper and middle rank castes show higher affinity to Europeans than do lower rank castes from either Tamil Nadu or Andhra Pradesh. Local between-caste variation (Tamil Nadu RST = 0.96%, Andhra Pradesh RST = 0.77%) exceeds the estimate of variation between these geographically separated groups (RST = 0.12%). Low, but statistically significant, correlations between caste rank distance and genetic distance are demonstrated for Tamil castes using Y-chromosome, mtDNA, and autosomal data. CONCLUSION: Genetic data from Y-chromosome, mtDNA, and autosomal STRs are in accord with historical accounts of northwest to southeast population movements in India. The influence of ancient and historical population movements and caste social structure can be detected and replicated in South Indian caste populations from two different geographic regions.

Cognitive dysfunction and associated factors in patients with chronic schizophrenia.

BACKGROUND: Deficits in neurocognitive function are a hallmark of schizophrenia. They are associated with clinical manifestations and the course of the illness. A study of cognitive dysfunction in Indian patients with schizophrenia is of significance in view of a more benign course and outcome of the illness in this region. AIM: To study cognitive deficits and associated factors in patients with chronic schizophrenia and compare them with those in the normal population. METHODS: We compared 100 patients with chronic schizophrenia with 100 matched normal controls on multiple measures of attention, executive function and memory. RESULTS: Compared to normal individuals, patients with schizophrenia performed poorly in all cognitive tests. Cognitive deficits in patients were related to gender, education, age, duration of illness, and presence of positive and negative symptoms. CONCLUSION: The neurocognitive profile of Indian patients with chronic schizophrenia resembles those of patients in developed countries.