Differential expression of HIF1A and its downstream target VEGFA in the main subtypes of renal cell carcinoma and their impact on patient survival.

Renal cell carcinoma (RCC) represents around 3% of all cancers, with the most frequent histological types being clear-cell RCC (ccRCC), followed by papillary (pRCC) and chromophobe (chRCC). Hypoxia-inducible factors (HIFs), which promote the expression of various target genes, including vascular endothelial growth factor (VEGF) and the high- affinity glucose transporter 1, have an important role in the pathogenesis of RCC. This study investigated the immunohistochemical expression of HIF-1α and VEGF-A, showing significantly higher HIF-1α nuclear expression in pRCC compared to ccRCC, while there was no significant difference in VEGF-A protein expression between the analyzed histological RCC subtypes. The quantitative reverse transcription polymerase chain reaction for HIF1A showed no statistical difference between histological types. Data from publicly available RNA sequencing databases were analyzed and showed that, compared to healthy kidney tissue, VEGFA was significantly up-regulated in ccRCC and significantly down-regulated in pRCC. The comparison between histological subtypes of RCC revealed that VEGFA was significantly up-regulated in ccRCC compared to both pRCC and chRCC. There was no statistically significant difference in survival time between HIF1A high- and low-expression groups of patients. As for VEGFA expression, pRCC patients with low expression had a significantly higher survival rate compared to patients with high VEGFA expression.

The Effect of GLUT1 and HIF-1α Expressions on Glucose Uptake and Patient Survival in Non-Small-Cell Lung Carcinoma.

Lung cancer is the second-most-common cancer while being the leading cause of cancer deaths worldwide. It has been found that glucose transporter 1 (GLUT1) and hypoxia-inducible factor 1α (HIF-1α) are overexpressed in various malignancies and that they correlate with the maximum standard uptake values (SUVmax) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) and poor prognosis. In this study, we aim to evaluate the relationship between the SUVmax, GLUT1, and HIF-1α expression with primary tumor size, histological type, lymph node metastases, and patient survival. Of the 48 patients with non-small-cell lung cancer, those with squamous cell carcinomas (SCCs) had significantly higher GLUT1 and HIF-1α immunohistochemical expressions in comparison to adenocarcinomas (ACs), while there was no statistically significant difference in FDG accumulation between them. No significant correlation was noted between either GLUT1 or HIF-1α protein expression and FDG uptake and overall survival. However, an analysis of tumor transcriptomics showed a significant difference in overall survival depending on mRNA expression; patients with SCC and high HIF-1α levels survived longer compared to those with low HIF-1α levels, while patients with AC and low GLUT1 levels had a higher average survival time than those with high GLUT1 levels. Further studies are needed to determine the prognostic value of the expression of these factors depending on the histologic type.

Determining the immunohistochemical expression of GLUT1 in renal cell carcinoma using the HSCORE method.

The aim of the present study was to compare the immunohistochemical expression of glucose transporter 1 (GLUT1) between the most common histological types of renal cell carcinoma (RCC), and to determine whether a correlation between GLUT1 expression and nuclear grade or tumor size exists. A total of 19 RCC samples were selected for the study, consisting of 8 clear cell (cc)RCC and 11 non-ccRCC tissues. Immunohistochemistry for GLUT1 was performed on formalin-fixed and paraffin-embedded sections using GLUT1 antibodies. All data analyses were performed using the MedCalc software. There was a higher immunohistochemical expression of GLUT1 in the ccRCC group compared with the non-cc group, but there was no difference in GLUT1 expression between groups of RCCs with differing nuclear grades. No significant correlation between GLUT1 expression and tumor size was found. The higher immunohistochemical expression of GLUT1 in ccRCC may be a contributing factor to the clinical characteristics and behavior of that group of carcinomas. These results suggest that GLUT1 expression cannot be used as a prognostic factor for RCC, but it may be used as a predictive factor in the future.

Adjuvant Chemotherapy in Locally Advanced Cervical Cancer After Treatment with Concomitant Chemoradiotherapy--Room for Improvement?

BACKGROUND: The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy. In the majority of patients with LACC after properly executed concomitant chemoradiotherapy local control of the disease is achieved, and consequently distant relapse becomes the main cause of death for these patients. In an attempt to improve the outcome of patients with LACC, we designed a regimen of concomitant chemobrachyradiotherapy with cisplatin and ifosfamide followed by consolidation chemotherapy. PATIENTS AND METHODS: Between 1999 and 2012, 118 patients diagnosed with LACC, The International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IVA, regardless of histology, were treated with concomitant chemobrachyradiotherapy and consolidation chemotherapy at our Institution. Chemotherapy consisted of two cycles of cisplatin and ifosfamide applied concomitantly with two intracavitary low-dose rate brachytherapy applications, and of four cycles of the same drug combination as an adjuvant/consolidation part of the treatment. The primary outcome in this analysis was distant disease-specific survival. RESULTS: A total of 18 patients had documented relapse of cervical cancer, with only three local recurrences observed; 15 patients developed only distant recurrence, and one patient developed both local and distant recurrence. The distant disease-specific survival after a median follow-up of 96 months was 86.4%. CONCLUSION: Consolidation or adjuvant chemotherapy that follows concomitant chemoradiotherapy has a potential role in further improving control of the disease, especially distant control of the disease.

Long follow-up of patients with locally advanced cervical cancer treated with concomitant chemobrachyradiotherapy with cisplatin and ifosfamide followed by consolidation chemotherapy.

OBJECTIVES: Locally advanced cervical cancer (LACC) is one of the leading health problems of the developing countries. We present long-term outcomes of treatment with a concomitant chemobrachyradiotherapy followed by consolidation chemotherapy regimen. MATERIALS AND METHODS: We treated 118 patients with LACC (International Federation of Gynecology and Obstetrics stages IB2-IVA) with external radiotherapy (50 Gy in 25 fractions) and concomitant chemobrachyradiotherapy (low-dose rate). Chemotherapy was applied during brachyradiotherapy (cisplatin on day 1 in combination with 24-hour infusion of ifosfamide and mesna uroprotection). Four cycles of consolidation chemotherapy were given starting 4 weeks after the second concomitant chemobrachyradiotherapy cycle. RESULTS: After median follow-up period of 99.3 months, we observed acceptable acute and late toxicity, local control rate of 97.5%, and an overall survival of 74.6% at 96 months. CONCLUSIONS: Chemobrachyradiotherapy regimen followed by consolidation chemotherapy described in this article is a valuable treatment option for LACC.