Reduced expression of microRNA122 (miR122), a liver-specific microRNA, is frequent in hepatocellular carcinoma (HCC). However, its biological significances remain poorly understood. Because deregulated amino acid levels in cancers can affect their biological behavior, we determined the amino acid levels in miR122-silenced mouse liver tissues, in which intracellular arginine levels were significantly increased. The increased intracellular arginine levels were through upregulation of the solute carrier family 7 (SLC7A1), a transporter of arginine and a direct target of miR122. Arginine is the substrate for nitric oxide (NO) synthetase, and intracellular NO levels were increased in miR122-silenced HCC cells, with increased resistance to sorafenib, a multikinase inhibitor. Conversely, maintenance of the miR122-silenced HCC cells in arginine-depleted culture media, as well as overexpression of miR122 in miR122-low-expressing HCC cells, reversed these effects and rendered the cells more sensitive to sorafenib. Using a reporter knock-in construct, chemical compounds were screened, and Wee1 kinase inhibitor was identified as upregulators of miR122 transcription, which increased the sensitivity of the cells to sorafenib. These results provide an insight into sorafenib resistance in miR122-low HCC, and suggest that arginine depletion or a combination of sorafenib with the identified compound may provide promising approaches to managing this HCC subset.

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Background: Postoperative irradiation for brain tumor in pregnant women is a matter of concern. Aim: We aimed to assess the safety of radiotherapy for brain tumors in pregnancy. We here report a successful treatment for anaplastic astrocytoma during pregnancy: surgery + postoperative irradiation. We wish to emphasize how we devised irradiation procedure to achieve both therapeutic effectiveness and safety to the fetus/infant. Case Presentation: A 34-year-old pregnant woman suffered with brain anaplastic astrocytoma. Tumor resection under craniotomy was performed with success. We decided to conduct postoperative radiotherapy at 25 weeks of gestation to reduce the risk of recurrence. We used a flattening filter-free volumetric arc therapy (FFF-VMAT) technique, which can achieve lower out-of-field dose than VMAT with a flattening filter or helical tomotherapy. We prescribed 60 Gy over 30 fractions. During actual beam delivery, surface and rectal dose to the patient (mother) were measured. The total fetal dose was estimated at 0.006-0.018 Gy, which is under the threshold set by the ICRP. A male healthy infant was born vaginally at the 37th week of pregnancy. The patient (mother) and the infant are healthy at the time of writing. Conclusion: FFF-VMAT is a good choice for brain tumors during pregnancy.

BackgroundBreathing motion management is the key to delivering stereotactic body radiation therapy (SBRT) for liver lesions. This study aimed to compare the dosimetric parameters of liver SBRT using two different techniques: free breathing and breath hold. MethodThe study included 11 patients with liver metastases or hepatocellular carcinoma who underwent liverdirected SBRT. A dosimetric comparison was performed using dose-volume histogram analysis, evaluating parameters such as the maximum dose to 5 cc of bowel volume, mean liver dose (MLD), and liver V20 and V30. Statistical analyses were performed to compare results. ResultsThe findings revealed that the breath hold technique resulted in significantly lower doses to the bowel and smaller volumes of normal liver tissue receiving 20 Gy (V20) and 30 Gy (V30) than the free breathing. Although there was no statistically significant difference in the MLD between the two techniques, the breath hold technique resulted in a lower MLD. ConclusionThis dosimetric comparison study suggests that the breath hold technique is associated with lower radiation exposure to the bowel and normal liver tissues. Although this may not be feasible for all patients, it may be an appropriate procedure for selected individuals. Further research is needed to validate these findings in different patient populations and explore their impact on clinical outcomes and patient-reported quality of life.