SummaryTo understand the role of p53 tumour suppressor gene in the carcinogenesis of arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan, we collected tumour samples from 23 patients with Bowen's disease, seven patients with basal cell carcinomas (BCC) and nine patients with squamous cell carcinomas (SCC). The result showed that p53 gene mutations were found in 39% of cases with Bowen's disease (9/23), 28.6% of cases with BCC (2/7) and 55.6% of cases with SCC (5/9). Most of the mutation sites were located on exon 5 and exon 8. Moreover, the results from direct sequencing indicated that missense mutations were found at codon 149 (C→T) in one case, codon 175 (G→A) in three cases, codon 273 (G→C) in three cases, codon 292 (T→A) in one case, codon 283 (G→T) in one case, codon 172 (T→C) in one case and codon 284 (C→A) in one case. In addition, silent mutations were also found in four cases. These mutations were located at codons 174, 253, 289 and 298 respectively. In immunohistochemistry analysis, p53 overexpression was found in 43.5% (10/23) of cases with Bowen's disease, 14% (1/7) of cases with BCC and 44% (4/9) of cases with SSC. These findings showed that p53 gene mutation rate in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan is high and that the mutation types are different from those in UV-induced skin cancers.

There is high risk of metastasis and recurrence in head and neck squamous cell carcinoma (HNSCC) patients, especially for patient who received definitive surgery and adjuvant radiotherapy. Aberrant activation of PI3K/AKT/mTOR signaling occurs in approximately 80% of HNSCC, which has been indicated to serve as prognostic biomarkers for patients suffer from recurrence or metastasis. Therefore, in this study, we focus on the relationship between the expression level of signaling factors in PI3K/AKT/mTOR pathway and recurrence tumor from HNSCC patients. A tissue microarray (TMA) was constructed from 54 cases of HNSCC patients who received definitive surgery and adjuvant radiotherapy, are followed more than 5 years, and with no previous malignancy and synchronous tumor. Slides were scored and dichotomized by two pathologists and scores. Based on the TMA block with IHC staining, the results showed that PI3K/AKT/mTOR signaling was highly activated both in recurrence and non-recurrence patients. Particularly, in the recurrence population, the results showed the low expression phospho-eukaryotic initiation factor 4E (p-eIF4E) or high expression eIF4E, phospho-eIF4E binding protein 1 (p-4EBP1), phospho-ribosomal protein S6 kinase beta-1 (p-S6K1) and phospho-40S ribosomal protein S6 (p-S6R) exhibited worse overall survival. The expression level of eIF4E and p-4EBP1 were significantly associated with tumor recurrence and recurrence-free survival. Furthermore, high expression level of eIF4E and p-4EBP1 had worse recurrence-free survival. In conclusion, the expression of eIF4E and p-4EBP1 should be considered as predictive biomarkers for the HNSCC patients. This may contribute to potential predictive biomarkers for HNSCC patient who receive adjuvant radiotherapy.

Our previous studies have shown that seven out of 15 patients with adrenocortical tumours contained K- ras gene mutation. In addition, the mutation type was a multiple-site mutation, and the hot spots were located at codons 15, 16, 18 and 31, which were different from those reported before (codons 12, 13 and 61). To understand whether the mutation hot spots in human adrenocortical tumours were associated with activation of K- Ras oncogene and the alterations of its biocharacteristics, mutant K- Ras genes were cloned from tumour tissues and then constructed with expression vector pBKCMV. Mutant K- Ras genes were expressed at high levels in Escherichia coli and the resultant K- Ras proteins were shown to be functional with respect to their well-known specific, high-affinity, GDP/GTP binding. The purified K- Ras protein from E. coli were then measured for their intrinsic GTPase activity and the GTPase activity in the presence of GTPase-activating protein for Ras. The results showed that the wild-type cellular K- Ras protein (p21BN) exhibits about ten times higher intrinsic GTPase activity than the activated protein (p21BM3) encoded by mutant K- Ras gene, which mutated at codon 60. With regards to the codon 15, 16, 18 and 31 mutant K- Ras proteins (p21BM2), the GTPase activity in the presence of GAP is much lower than that of the normal K- Ras protein, whereas the intrinsic GTPase activity is nearly the same as that of the normal K- Ras protein. These results indicated that mutations at these hot spots of K- Ras gene were indeed activated K- Ras oncogene in adrenocortical tumours; however, their association with tumors needs further experiments to prove. © 2000 Cancer ResearchCampaign

Nutritional assessments, including the Geriatric Nutritional Risk Index (GNRI), have emerged as prediction tools for long-term survival in various cancers. This study aimed to investigate the therapeutic strategy and explore the prognostic factors in the elderly patients (≥ 65 years) with diffuse large B cell lymphoma (DLBCL). The cutoff value of the GNRI score (92.5) was obtained using the receiver operating characteristic curve. Among these patients (n = 205), 129 (62.9%) did not receive standard R–CHOP chemotherapy. Old age (≥80 years), poor performance status, low serum albumin level, and comorbidities were the major factors associated with less intensive anti-lymphoma treatment. Further analysis demonstrated that a lower GNRI score (<92.5) was linked to more unfavorable clinical features. In the patients who received non-anthracycline-containing regimens (non-R–CHOP), multivariate analysis showed that a low GNRI can serve as an independent predictive factor for worse progression-free (HR, 2.85; 95% CI, 1.05–7.72; p = 0.039) and overall survival (HR, 2.98; 95% CI, 1.02–8.90; p = 0.045). In summary, nutritional evaluation plays a role in DLBCL treatment and the GNRI score can serve as a feasible predictive tool for clinical outcomes in frail elderly DLBCL patients treated with non-anthracycline-containing regimens.