KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer

5-Fluorouracil (5-FU) is one of the most frequently used pharmacological agents in the treatment of colorectal cancer (CRC). Resistance to chemotherapy is a major cause of treatment failure of CRC, and it is a well known fact that cancer stem cells play a significant role in the acquisition of drug resistance. In this study, we focused on the KHDRBS3 gene that encodes KH RNA Binding Domain Containing, Signal Transduction Associated 3. We first clarified the relationship between KHDRBS3 and 5-FU resistance. We then observed higher expression levels of KHDRBS3 in KRAS-mutant organoids and cell lines in comparison with KRAS wild-type organoids and cell lines. Immunohistochemical analysis using CRC cases revealed that the prognosis of KHDRBS3-positive patients was significantly worse compared with that of KHDRBS3-negative patients. Univariate and multivariate Cox proportional hazards analyses showed that KHDRBS3 was an independent prognostic factor in patients with CRC. We determined that KHDRBS3 might play a crucial role in the acquisition of stem cell properties, such as drug resistance and spheroid/organoid formation, by regulating CD44 variant expression and the Wnt signaling pathway. In an immunodeficient mouse model, KHDRBS3-positive cells showed efficient tumor formation and formed metastatic lesions in the lungs. These results indicated that KHDRBS3 plays a crucial role in drug resistance and anchorage-independent growth by maintaining stem cell-like features in CRC cells. KHDRBS3 could be a promising candidate marker for predicting chemotherapeutic effect and prognosis in CRC patients.     

Characteristic endoscopic findings of gastric adenocarcinoma of fundic-gland mucosa type

Gastric Cancer - Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland...     

KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria

Cyanobacterial clock proteins KaiA and KaiC are proposed as positive and negative regulators in the autoregulatory circadian kaiBC expression, respectively. Here, we show that activation of kaiBC expression by kaiA requires KaiC, suggesting a positive feedback control in the cyanobacterial clockwork. We found that robust circadian phosphorylation of KaiC. KaiA was essential for in vivo KaiC phosphorylation and activated in vitro KaiC autophosphorylation. These effects of KaiA were attenuated by the kaiA2 long period mutation. Both the long period phenotype and the abnormal KaiC phosphorylation in this mutant were suppressed by a previously undocumented kaiC mutation. We propose that KaiA-stimulated circadian KaiC phosphorylation is important for circadian timing.     

Normal delivery following an uneventful pregnancy in a Japanese acromegalic patient after discontinuation of octreotide long acting release formulation at an early phase of pregnancy

We report a 35-year-old woman with active acromegaly despite pituitary surgery and irradiation who received continuous octreotide LAR treatment for the control of GH excess until discovery of her pregnancy. The patient delivered a healthy boy following an uneventful pregnancy after discontinuing octreotide LAR as soon as possible at the early phase of pregnancy. Despite a substantial maternal-fetal transfer of octreotide, postnatal development was normal at 3 years of age. In almost all previously described cases, octreotide was discontinued after pregnancy was confirmed. No side-effects of mother or fetus have been reported. Octreotide treatment in pregnancy seems to be feasible and safe. Due to the still-limited number of reported cases treated with octreotide LAR, the potential benefits of octreotide LAR treatment should be weighed carefully against its possible risks.     

CT-based automated planning of acetabular cup for total hip arthroplasty (THA) based on hybrid use of two statistical atlases

Purpose

This study describes the use of CT images in atlas-based automated planning methods for acetabular cup implants in total hip arthroplasty (THA). The objective of this study is to develop an automated cup planning method considering the statistical distribution of the residual thickness.

Methods

From a number of past THA planning datasets, we construct two statistical atlases that represent the surgeon’s expertise. The first atlas is a pelvis-cup merged statistical shape model (PC-SSM), which encodes global spatial relationships between the patient anatomy and implant. The other is a statistical residual thickness map (SRTM) of the implant surface, which encodes local spatial constraints of the anatomy and implant. In addition to PC-SSM and SRTM, we utilized the minimum thickness as a threshold constraint to prevent penetration.

Results

The proposed method was applied to the pelvis shapes segmented from CT images of 37 datasets of osteoarthritis patients. Automated planning results with manual segmentation were compared to the plans prepared by an experienced surgeon. There was no significant difference in the average cup size error between the two methods (1.1 and 1.2 mm, respectively). The average positional error obtained by the proposed method, which integrates the two atlases, was significantly smaller (3.2 mm) than the previous method, which uses single atlas (3.9 mm). In the proposed method with automated segmentation, the size error of the proposed method for automated segmentation was comparable (1.1 mm) to that for manual segmentation (1.1 mm). The average positional error was significantly worse (4.2 mm) than that using manual segmentation (3.2 mm). If we only consider mildly diseased cases, however, there was no significance between them (3.2 mm in automated and 2.6 mm in manual segmentation).

Conclusion

We infer that integrating PC-SSM and SRTM is a useful approach for modeling experienced surgeon’s preference during cup planning.