This article introduces one of South Asia's most important border regions into academic discourse, namely, the Central Himalayan mountain rim separating India and the Tibetan Autonomous Region (People's Republ...This article introduces one of South Asia's most important border regions into academic discourse, namely, the Central Himalayan mountain rim separating India and the Tibetan Autonomous Region (People's Republic of China). What makes this border region so interesting is a tangled interplay of changing environmental, cultural, and political forms to which the local populations constantly have to adapt in order to make a living there. We focused on the so-called 'Bhotiyas' of Uttarakhand, former trans-Himalayan traders whose ethnicity and livelihood was traditionally associated with the Indo-Chinese border that was sealed as a result of the India-China war in 1962. Drawing on the work of borderland scholarship, we identified the key processes and developments that changed the perspective of this area. Competing political aspirations as well as the 'Bhotiyas' countervailing strategies were considered equally important for understanding local livelihoods and identities within the dynamics of a 'high mountain border region'. Through an exemplary analysis of historical differences of power in one 'Bhotiya' valley, we further explored the ways in which shifting socio-spatial constellations are creatively re-interpreted by the borderlanders.展开更多
BACKGROUND Head and neck squamous cell carcinoma(HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine k...BACKGROUND Head and neck squamous cell carcinoma(HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases(RTKs) and members of the fibroblast growth factor receptors(FGFR)-family. Singlenucleotide polymorphism(SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC.AIM To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted.METHODS Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany.Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP.Patients' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis.RESULTS Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high"(+++) in 74(26%),"intermediate"(++) in 103(36.3%), and "low"(+) in 107(36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors(33.8%), 84 of them(29.6%) having a heterozygous and 12(4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage(P < 0.004), local metastasis(P < 0.0001) and reduced disease-free survival(P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival(P < 0.003).CONCLUSION In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention.展开更多
文摘This article introduces one of South Asia's most important border regions into academic discourse, namely, the Central Himalayan mountain rim separating India and the Tibetan Autonomous Region (People's Republic of China). What makes this border region so interesting is a tangled interplay of changing environmental, cultural, and political forms to which the local populations constantly have to adapt in order to make a living there. We focused on the so-called 'Bhotiyas' of Uttarakhand, former trans-Himalayan traders whose ethnicity and livelihood was traditionally associated with the Indo-Chinese border that was sealed as a result of the India-China war in 1962. Drawing on the work of borderland scholarship, we identified the key processes and developments that changed the perspective of this area. Competing political aspirations as well as the 'Bhotiyas' countervailing strategies were considered equally important for understanding local livelihoods and identities within the dynamics of a 'high mountain border region'. Through an exemplary analysis of historical differences of power in one 'Bhotiya' valley, we further explored the ways in which shifting socio-spatial constellations are creatively re-interpreted by the borderlanders.
文摘BACKGROUND Head and neck squamous cell carcinoma(HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases(RTKs) and members of the fibroblast growth factor receptors(FGFR)-family. Singlenucleotide polymorphism(SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC.AIM To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted.METHODS Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany.Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP.Patients' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis.RESULTS Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high"(+++) in 74(26%),"intermediate"(++) in 103(36.3%), and "low"(+) in 107(36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors(33.8%), 84 of them(29.6%) having a heterozygous and 12(4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage(P < 0.004), local metastasis(P < 0.0001) and reduced disease-free survival(P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival(P < 0.003).CONCLUSION In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention.