Mutation Analysis of Radioresistant Early-Stage Cervical Cancer.

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRASmt/SMAD4mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRASmt/SMAD4mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRASmt/SMAD4mt cancer cells. These data indicate that the KRASmt/SMAD4mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRASmt/SMAD4mt signature.

Motor cortex somatotopic presentation after restriction of neck movement in rats.

[Purpose] In this study, we aimed to investigate the effects of neck movement restriction on somatotopic mapping of the motor cortex. We restricted cervical extension for two weeks and investigated the effects on motor cortex somatic representation in rats. [Subjects and Methods] We placed six Wistar rats into each of three groups: (i) the experimental group, in which cervical extension was restricted; (ii) the sham group, in which cervical movement was not restricted, but a splint was placed in the shoulder girdle; and (iii) the control group. After cervical immobilization for two weeks, we evaluated the motor cortex somatic representation using intra-cortical micro-stimulation. [Results] In the experimental group, the areas of the cervical and vibrissal domains of the motor cortex decreased by approximately 50%, and the forelimb domain showed slight reduction. In addition, a trunk domain formed at the locus of the vibrissal area. There were no differences between the sham and control groups. [Conclusion] Restriction of cervical extension for two weeks resulted in changes in motor cortex somatic representation. Reversible changes occurred in cortical areas that controlled the neck and parts of the body involved in cervical movement.

Neck and trunk representations in the primary motor cortex in rats.

[Purpose] The neck and trunk play crucial roles in body movement and are extremely important areas of treatment for physical therapists. However, many aspects of the neural basis of this motor control remain unknown. Therefore, we investigated the distribution and electrophysiological properties of the neck and trunk in the primary motor cortex in rats. [Subjects and Methods] Using intracortical microstimulation, we investigated the somatotopic representation and movements induced by electrical stimulation of the neck and truck areas of the motor cortex in 8 Wistar rats. [Results] We determined that the neck and trunk areas are located separately on the rostral and caudal sides of the motor cortex, respectively. The neck area was significantly larger in size, while the threshold was significantly larger for the trunk area. Stimulation of the neck area with a current higher than the threshold induced movement of the forelimbs, jaw, trunk, and whiskers. However, stimulation of the trunk area did not result in movement in sites other than the trunk. [Conclusion] During movement, the respective activities of the neck and trunk are interdependent. However, due to the separate locations of these areas in the motor cortex, their properties differ greatly.