The use of low power ultrasound in therapeutic medicine is a developing field and this review will concentrate on the applications of this technology in cancer therapy. The effects of low power ultrasound have been evaluated in terms of the biological changes induced in the structure and function of tissue. The main fields of study have been in sonodynamic therapy, improving chemotherapy, gene therapy and apoptosis therapy. The range of ultrasonic power levels that can be effectively employed in therapy appears to be narrow and this may have hindered past research in the applications in cancer treatment.

Eighty kidneys (40 left and 40 right kidneys) of New Zealand rabbits were ablated using high intensity focused ultrasound (HIFU), (14,300 W/cm(2), 1.0 MHz). Kidneys were randomly divided into two groups. HIFU was performed in the manner of linear scan in both groups. Prior to HIFU, normal saline solution and isovolumetric microbubble agent were administrated intravenously in groups I and II, respectively. HIFU was finished in all left kidneys and in 26/40 right ones. The therapeutic efficiency was reflected using necrosis rate (cubic centimeters per second), which was the tissue volume of coagulative necrosis per 1 s HIFU exposure. In both groups, predetermined volumes were damaged without harming overlying tissues. Necrosis rates were increased in group II both in left (0.0089+/-0.0107 vs. 0.0493+/-0.0777, P=0.0323) and in right (0.0039+/-0.0055 vs. 0.0162+/-0.0168, P=0.0248) kidneys. Pathological examinations confirmed that there were no intact tissue focuses within exposed regions in either group. These findings suggested that the microbubble agent improved the therapeutic efficiency of HIFU. Hemorrhage and hyperemia were also detected on the margin of the ablated tissues (both in cortex and medulla) in both groups.

Ultrasound: A Chemotherapy Sensitizer www.tcrt.orgChemotherapy plays a very important role in cancer treatment. However, there are still some barriers in the successful use of such therapies, mainly because of the adverse side effects of the anticancer agents and due to the development of chemoresistance. This paper focuses on the use of ultrasound to enhance chemotherapy and to overcome drug resistance. The action of many anticancer agents can be improved with the use of ultrasonic exposure either in vitro or in vivo. Drug resistance can be circumvented using ultrasound alone. Furthermore, the reversal attributable to chemoresistance modifiers, such as verapamil and PSC 833, is augmented by ultrasound. Ultrasound-mediated chemosensitization is usually achieved via increasing intracellular drug accumulation, although other mechanisms are also involved. Ultrasound also can play a role in targeted chemotherapy, releasing anticancer chemicals directly and efficiently into the lesions. However, this promising modality has not been clinically adopted so far and the reasons are discussed.

Abstract. The Forkhead box O (FOXO) protein family is predominantly involved in apoptosis, oxidative stress, DNA damage/repair, tumor angiogenesis, glycometabolism, regulating life span and other important biological processes. Its activity is affected by a variety of posttranslational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, methylation and glycosylation. When cells are subjected to different environments, the corresponding PTMs act on the FOXO protein family, to change transcriptional activity or subcellular localization, and the expression of downstream target genes, will ultimately affect the biological behavior of the cells. In this review, we will discuss the biological characteristics of FOXO protein PTMs.

BackgroundHigh-intensity focused ultrasound (HIFU) is considered to be an alternative to surgery. Extracorporeal ultrasound-guided HIFU (USgFU) has been clinically used to treat solid tumors. Preliminary trials in a small sample of a Western population suggested that this modality was safe. Most trials are performed in China thereby providing comprehensive data for understanding the safety profile. The aim of this study was to evaluate adverse events of USgFU therapy.Methods and FindingsClinical data were searched in 2 Chinese databases. Adverse events of USgFU were summarized and compared with those of magnetic resonance-guided HIFU (MRgFU; for uterine, bone or breast tumor) and transrectal ultrasound-guided HIFU (for prostate cancer or benign prostate hyperplasia). USgFU treatment was performed using 7 types of device. Side effects were evaluated in 13262 cases. There were fewer adverse events in benign lesions than in malignant lesions (11.81% vs. 21.65%, p<0.0001). Rates of adverse events greatly varied between the disease types (0–280%, p<0.0001) and between the applied HIFU devices in both malignant (10.58–44.38%, p<0.0001) and benign lesions (1.67–17.57%, p<0.0001). Chronological analysis did not demonstrate a decrease in the rate of adverse events. Based upon evaluable adverse events, incidences in USgFU were consistent with those in MRgFU or transrectal HIFU. Some side effects frequently occurred following transrectal HIFU were not reported in USgFU. Several events including intrahepatic metastasis, intraoperative high fever, and occlusions of the superior mesenteric artery should be of particular concern because they have not been previously noted. The types of adverse events suggested that they were ultrasonic lesions.ConclusionThe frequency of adverse events depended on the location of the lesion and the type of HIFU device; however, side effects of USgFU were not yet understood. USgFU did not decrease the incidence of adverse events compared with MRgFU.

The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the ATP-binding cassette (ABC) transporter family, members of which are involved in various types of cancer. The relationship between CFTR and ovarian cancer remains to be elucidated. The aim of the present study was to investigate the expression of CFTR in human ovarian cancer tissues and its clinical significance in the progression of ovarian cancer. The role of CFTR in the malignant invasion, migration and proliferation of ovarian cancer in vitro and in vivo was also investigated. Immunohistochemical staining analysis was performed to detect the expression of CFTR in 83 cases of human epithelial ovarian cancer specimens. Moreover, SKOV3 and A2780 stable cell lines containing shRNA gene specific for CFTR were established. Cell proliferation and motility were observed and compared with CFTR-RNAi cells. Tumorigenicity of CFTR-RNAi cells was investigated by tumor xenograft experiments conducted subcutaneously in nude mice. The expresssion of CFTR in ovarian cancer was significantly higher than that in benign ovarian tumor and normal ovaries (P<0.05). In ovarian cancer, CFTR expression was significantly associated with advanced FIGO stage, poor histopathological grade and serum Ca-125 (P<0.05). Furthermore, we observed that CFTR staining was stronger in the serous type as compared to the other types (P<0.05). Compared with the negative control, decreased cell invasion, migration, proliferation, adhesion and colony formation were observed in CFTR-RNAi cells in vitro. In vivo, tumorigenic abilities of CFTR-RNAi cells were significantly repressed compared with that of the control groups. CFTR overexpression may play an important role in the development and progression of ovarian cancer. Additionally, the downregulation of CFTR suppresses aggressive malignant biological behaviors of ovarian cancer cells in vitro and in vivo.

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Membrane-associated RING-CH (MARCH) belongs to the family of RING-CH type E3 ubiquitin ligases. MARCH1 ubiquitinates and downregulates MHC class II expression in APCs and targets major players of the immune system. However, the role of MARCH1 in ovarian cancer has not been elucidated. The present study investigated the function of MARCH1 in ovarian cancer and the potential mechanisms involved. MARCH1 expression was examined in human ovarian cancer tissue specimens by immunohistochemistry. The role of MARCH1 in ovarian cancer cells was assessed by cell proliferation, migration and invasion assays with MARCH1 gene silencing. To investigate the mechanism by which MARCH1 functions, correlation between MARCH1 and the cell signaling pathways were analyzed using a luciferase reporter assay, real-time RT-PCR, western blot assay and immunofluorescence. MARCH1 was found to be overexpressed in ovarian cancer tissues when compared to adjacent non-tumor and normal ovarian tissues. Silencing MARCH1 inhibited SKOV3 cell proliferation, invasion and migration, as well as inhibiting the NF-κB and the Wnt/β-catenin pathways. MARCH1 functions as a tumor promoter by upregulating the NF-κB and the Wnt/β-catenin pathways, indicating that MARCH1 may be a therapeutic target for patients with ovarian cancer.