Background: Tumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood.Methodology: The metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The expressions of pH regulators in TECs and NECs were determined by quantitative reverse transcription-PCR. Cell proliferation was measured by the MTS assay. Western blotting and ELISA were used to validate monocarboxylate transporter 1 and carbonic anhydrase 2 (CAII) protein expression within the cells, respectively. Human tumor xenograft models were used to access the effect of CA inhibition on tumor angiogenesis. Immunohistochemical staining was used to observe CAII expression, quantify tumor microvasculature, microvessel pericyte coverage, and hypoxia.Results: The present study shows that, unlike NECs, TECs proliferate in lactic acidic. TECs showed an upregulated CAII expression both in vitro and in vivo. CAII knockdown decreased TEC survival under lactic acidosis and nutrient-replete conditions. Vascular endothelial growth factor A and vascular endothelial growth factor receptor signaling induced CAII expression in NECs. CAII inhibition with acetazolamide minimally reduced tumor angiogenesis in vivo. However, matured blood vessel number increased after acetazolamide treatment, similar to bevacizumab treatment. Additionally, acetazolamide-treated mice showed decreased lung metastasis.Conclusion: These findings suggest that due to their effect on blood vessel maturity, pH regulators like CAII are promising targets of antiangiogenic therapy.Graphical

Objectives: The aim of the study is to evaluate the impact of nephron–sparing surgery on postoperative quality of life (QOL) in patients with localized renal cell carcinoma, compared with radical nephrectomy. Methods: From 1986 to 1996, a total of 66 patients with localized small renal cell carcinoma <4 cm in diameter and a functioning contralateral renal unit underwent radical nephrectomy (n = 51) or nephron–sparing surgery (n = 15). Of these, 50 patients evaluated various dimensions of QOL using standardized self–rating questionnaires, EORTC QLQ–C30. Results: There is no significant difference in 5–year overall survival between the nephron–sparing surgery group and the radical nephrectomy group. With regard to postoperative QOL, patients who underwent nephron–sparing surgery showed a significantly higher score on physical function than patients treated with radical nephrectomy (p<0.05). Nephron–sparing surgery was additionally superior to radical nephrectomy in terms of fatigue, sleep disturbance, pain and constipation. Conclusion: Selected patients with localized, small, unilateral renal cell carcinoma and a normal contralateral kidney will benefit from nephron–sparing surgery.

To clarify the relationship between the probability of prostate cancer scaled using a 5-point Likert system and the biological characteristics of corresponding tumor foci. The present study involved 44 patients undergoing 3.0-Tesla multiparametric MRI before laparoscopic radical prostatectomy. Tracing based on pathological and MRI findings was performed. The relationship between the probability of cancer scaled using the 5-point Likert system and the biological characteristics of corresponding tumor foci was evaluated. A total of 102 tumor foci were identified histologically from the 44 specimens. Of the 102 tumors, 55 were assigned a score based on MRI findings (score 1: n = 3; score 2: n = 3; score 3: n = 16; score 4: n = 11 score 5: n = 22), while 47 were not pointed out on MRI. The tracing study revealed that the proportion of >0.5 cm3 tumors increased according to the upgrade of Likert scores (score 1 or 2: 33 %; score 3: 68.8 %; score 4 or 5: 90.9 %, χ2 test, p < 0.0001). The proportion with a Gleason score >7 also increased from scale 2 to scale 5 (scale 2: 0 %; scale 3: 56.3 %; scale 4: 72.7 %; 5: 90.9 %, χ2 test, p = 0.0001). On using score 3 or higher as the threshold of cancer detection on MRI, the detection rate markedly improved if the tumor volume exceeded 0.5 cm3 (<0.2 cm3: 10.3 %; 0.2-0.5 cm3: 25 %; 0.5-1.0 cm3: 66.7 %; 1.0 < cm3: 92.1 %). Each Likert scale favobably reflected the corresponding tumor’s volume and Gleason score. Our observations show that “score 3 or higher” could be a useful threshold to predict clinically significant carcinoma when considering treatment options.

The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.