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Several carbonic anhydrase (CA, EC 4.2.1.1) isoforms play an essential role in processes connected to tumorigenesis, as they efficiently accelerate the hydration of carbon dioxide to bicarbonate and proton. In this context, examples are CA IX and CA XII, which were proved to be upregulated in many solid malignancies. On the other hand, cancer and the immune system are inextricably linked, and targeting the immune checkpoints recently was shown to efficiently improve the treatment of malignancies. In this study, we have investigated the expression of CA isoforms in tumour-infiltrating lymphocytes (TILs) that, according to the immunosurveillance theory, were suggested to have a crucial role in the development of colorectal cancer (CRC). T lymphocytes isolated from healthy surrounding mucosa showed a higher CA activity compared to those present in tumour and peripheral blood in the same patients. CA I and II were confirmed as enzyme isoforms involved in the process, as determined by proteomic analysis of corresponding TIL samples. These preliminary findings suggest a dysregulation of the local immune response in the CRC tissues and a loss of effective anticancer mechanisms mediated by CAs therein.

Purpose: Bleeding from parenchyma transection during a robotic hepatic surgery remains the most critical point affecting postoperative recovery and long-term survival. Various robotic devices with different types of energies have been proposed; however, each of these lack in steerability, efficacy, or accuracy. The aim of this work is to evaluate the feasibility and performance of a new steerable microwave resection device intended for minimizing intraoperative blood loss during laparoscopic and robotic liver resections. Methods: The new device operating at 2.45 GHz was designed to accommodate the engineering constraints derived from its use for robotic surgery or laparoscopy, in which a steerable head is required and the internal cooling of forced gas or water is undesirable. The device design, analysis, and optimization were addressed using the most advanced commercial electromagnetic and thermal solvers to achieve the best results. To experimentally validate the results of the numerical analysis, many ablations were performed on a freshly explanted bovine liver by using a single device prototype with three levels of energy supplied to the tissue. During the ablation procedures, the time, temperature, and shape of the thermal lesion were recorded using thermocouples and an infra-red thermos camera. Summary: Ex vivo tests showed good agreement with the numerical simulations, demonstrating the validity of the simplifications adopted to deal with the complex phenomena involved in the extreme hyperthermia of a living tissue. The high performance, thermal reliability, and robustness of the developed device were also demonstrated along with the possibility of reducing operation time and blood loss.

Carbonic anhydrase (CA, EC 4.2.1.1) IX is regarded as a tumour hypoxia marker and CA inhibitors have been proposed as a new class of antitumor agents, with one such agent in Phase II clinical trials. The expression of some CAs, in particular the isoforms CA IX and CA XII, has been correlated with tumour aggressiveness and progression in several cancers. The aim of this study was to evaluate the possibility that CA IX could represent a marker related to clear cell Renal Cell Carcinoma (ccRCC). Bcl-2 and Bax, and the activity of caspase-3, evaluated in tissue biopsies from patients, were congruent with resistance to apoptosis in ccRCCs with respect to healthy controls, respectively. In the same samples, the CA IX and pro-angiogenic factor VEGF expressions revealed that both these hypoxia responsive proteins were strongly increased in ccRCC with respect to controls. CA IX plasma concentration and CA activity were assessed in healthy volunteers and patients with benign kidney tumours and ccRCCs. CA IX expression levels were found strongly increased only in plasma from ccRCC subjects, whereas, CA activity was found similarly increased both in plasma from ccRCC and benign tumour patients, compared to healthy volunteers. These results show that the plasmatic level of CA IX, but not the CA total activity, can be considered a diagnostic marker of ccRCCs. Furthermore, as many reports exist relating CA IX inhibition to a better outcome to anticancer therapy in ccRCC, plasma levels of CA IX could be also predictive for response to therapy.