Engineered T Cell Receptor for Cancer Immunotherapy.

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

Association of frailty with fall events in older adults: A 12-year longitudinal study in Korea.

BACKGROUND: Evidence has shown that frailty is associated with the risk of falls in older people. However, the components of frailty that have the highest association with fall events are largely unknown. METHODS: This study analyzed panel data from the Korean Longitudinal Study of Aging. We used the Korean Frailty Instrument, which includes domains for social isolation, exhaustion and weakness estimated by grip strength, to assess frailty. Fall event data were collected during follow-up visits. RESULTS: A total of 3122 community-dwelling adults aged 65 years or older were included at baseline in 2006 and were followed up every 2 years until 2018. The participants with frailty had a higher risk of falls than those without frailty (OR=1.31, 95% CI=1.11-1.54, P = 0.001; fully adjusted model). We found that three components of frailty, namely, social isolation, exhaustion, and weakness, were independently and significantly related to fall events in the unadjusted model. In the fully adjusted model, social isolation and exhaustion were significantly associated with fall events (OR=1.38, 95% CI=1.18-1.61, P < 0.001 and OR=1.28, 95% CI=1.10-1.51, P = 0.006, respectively), and there was no significant association between weakness and the risk of falls (OR=1.11, 95% CI=0.91-1.34, P = 0.307). CONCLUSIONS AND IMPLICATIONS: Frailty was associated with more fall events in Korean older adults. Social isolation and exhaustion but not weakness were significantly associated with fall events. Our study suggests that interventions should be tailored to older adults with social and psychological frailty.

Deciphering Clinicoradiologic Phenotype for Thymidylate Synthase Expression Status in Patients with Advanced Lung Adenocarcinoma Using a Radiomics Approach.

We aimed to identify predictive clinicoradiologic characteristics of thymidylate synthase (TS) expression status in advanced non-squamous non-small cell lung cancer patients. We reviewed clinicoradiologic features of 169 patients stratified into TS-negative (n = 84) and TS-positive (n = 85) groups, including quantitative CT radiomic features of both primary lung and metastatic lesions from initial CT and PET. Clinical factors including age and smoking history were significantly associated with TS as well as radiomic features. The predictive performance for dichotomizing TS expression status was slightly higher when imaging features of primary lung lesions were added compared to the model based solely on the clinical features, but without statistical significance (10-fold cross-validated AUC = 0.619 and 0.581, respectively; P = 0.425). The predictive performance of clinicoradiologic parameters slightly increased with primary lung lesions only compared to the inclusion of metastatic lesions, but without statistical significance (10-fold cross-validated AUC = 0.619 and 0.554, respectively; P = 0.203). Overall survival was prolonged in the TS-negative group compared to the TS-positive group (P = 0.001). TS-negativity is a potential prognostic biomarker, and our study presents that although CT radiomic features have potential for predicting TS expression status, clinical significance is uncertain. The addition of radiomic features to clinical factors did not show significant improvement in predicting TS-negativity.

Heterologous expression and enzymatic characterization of γ-glutamyltranspeptidase from Bacillus amyloliquefaciens.

γ-Glutamyltranspeptidase (GGT) catalyzes the cleavage of γ-glutamyl compounds and the transfer of γ-glutamyl moiety to water or to amino acid/peptide acceptors. GGT can be utilized for the generation of γ-glutamyl peptides or glutamic acid, which are used as food taste enhancers. In the present study, Bacillus amyloliquefaciens SMB469 with high GGT activity was isolated from Doenjang, a traditional fermented soy food of Korea. The gene encoding GGT from B. amyloliquefaciens SMB469 (BaGGT469) was cloned from the isolate, and heterologously expressed in E. coli and B. subtilis. For comparison, three additional GGT genes were cloned from B. subtilis 168, B. licheniformis DSM 13, and B. amyloliquefaciens FZB42. The BaGGT469 protein was composed of 591 amino acids. The final protein comprises two separate polypeptide chains of 45.7 and 19.7 kDa, generated via autocatalytic cleavage. The specific activity of BaGGT469 was determined to be 17.8 U/mg with γ-L-glutamyl-p-nitroanilide as the substrate and diglycine as the acceptor. GGTs from B. amyloliquefaciens showed 1.4- and 1.7-fold higher transpeptidase activities than those from B. subtilis and B. licheniformis, respectively. Especially, recombinant B. subtilis expressing BaGGT469 demonstrated 11- and 23-fold higher GGT activity than recombinant E. coli and the native B. amyloliquefaciens, respectively, did. These results suggest that BaGGT469 can be utilized for the enzymatic production of various γ-glutamyl compounds.

Improvement in imaging diagnosis technique and modalities for solitary pulmonary nodules: from ground-glass opacity nodules to part-solid and solid nodules.

With advances in CT technology and the popularity of low-dose CT as a device for lung cancer screening, the detection rate of sub-solid pulmonary nodules as well as solid nodules has been increased. Distinguishing solid from sub-solid features is an essential step in the CT evaluation of solitary pulmonary nodules (SPNs) because strategies for nodule characterization and guidelines for management are different for each category. In addition to conventional CT parameters, numerous novel concepts and modalities have been developed. Although there is currently no single effective method for differentiating malignant from benign nodules, growth rate measurement using volumetry, evaluation of tumor vascularity on dynamic helical CT, dual-energy CT and MRI and physiologic evaluation with PET/CT can all be useful for nodule characterization. New techniques such as tomosynthesis can improve detection over radiography alone. The purpose of this article is to enhance our understanding of the evidence-based strategies involved in diagnosing SPNs.

Combined Undifferentiated and Neuroendocrine Carcinomas of the Gallbladder Appearing as Two Separate Lesions: A Case Report with Radiological-Pathological Correlation.

We report herein a rare case of incidentally detected combined undifferentiated and neuroendocrine carcinomas of the gallbladder. An incidental gallbladder malignancy was revealed on abdominal ultrasound and multi-detector computed tomography in a 54-year-old man. A short distance from the main polypoid hypoechoic mass at the fundus of the gallbladder, focal wall thickening was noted with prominently increased power Doppler flow. Extended cholecystectomy was performed, and histology confirmed the main polypoid mass as undifferentiated carcinoma and the separate nodule as neuroendocrine carcinoma. To our knowledge, this is the first report presenting two separate lesions of combined gallbladder carcinomas by radiological features.

Role of CT and PET Imaging in Predicting Tumor Recurrence and Survival in Patients with Lung Adenocarcinoma: A Comparison with the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma.

INTRODUCTION: Recently, a new lung adenocarcinoma classification scheme was published. The prognostic value of this new classification has not been elaborated together with the value of imaging biomarkers including computed tomography (CT) and positron emission tomography (PET). METHODS: We reviewed pathologic specimens and imaging characteristics of primary tumors from 723 consecutive patients who underwent surgical resection for lung adenocarcinoma. On pathology, the predominant histologic subtype and pattern group were quantified. Tumor-shadow disappearance ratio (TDR) on CT and maximum standardized uptake value (SUVmax) on PET were assessed. The relationships between those variables and survival (overall survival [OS] and disease-free survival) were analyzed by using Kaplan-Meier curves and Cox regression analyses. RESULTS: The median follow-up period was 3.8 years. There were 137 patients (19%) with recurrence and 167 patients (23%) with metastasis after surgical resection. Among 723 patients, 35 patients (4.8%) had adenocarcinoma in situ, 34 patients (4.7%) had minimally invasive adenocarcinoma, 125 patients (17.3%) had lepidic predominant, 314 patients (43.4%) had acinar predominant, 65 patients (9.0%) had papillary predominant, 23 patients (3.2%) had micropapillary predominant, 113 patients (15.6%) had solid predominant, and 14 patients (1.9%) had variant adenocarcinomas. OS and disease-free survival rates were significantly different according to TDR on CT and SUVmax on PET, predominant subtypes, and pattern groups. On multivariate analysis, the SUVmax (p < 0.001), TDR (p = 0.038), and pattern group (p = 0.015) were independent predictors of OS. CONCLUSIONS: TDR on CT, SUVmax on PET, and the new histologic classification schemes appear to be promising parameters for the prognostic stratification of patients with lung adenocarcinomas, allowing for the triage of patients who necessitate further staging workup and adjuvant therapy.

Standard chest CT using combined automated tube potential selection and iterative reconstruction: image quality and radiation dose reduction.

OBJECTIVE: To evaluate the image quality and radiation dose reduction of chest computed tomography (CT) using combined automated tube potential selection (ATPS) and iterative reconstruction (IR). MATERIALS AND METHODS: Image quality and radiation dose were compared between conventional contrast-enhanced chest CT using 120 kVp and filtered back projection (Protocol A) and CT using ATPS and IR (Protocol B) in 43 patients. RESULTS: The effective radiation dose was 3.6 ± 0.4 mSv for Protocol A and 2.2 ± 0.6 mSv for Protocol B (mean dose reduction, 39.7%). Protocol B showed diagnostic image quality in all patients. CONCLUSION: ATPS and IR allows for radiation dose reduction while maintaining diagnostic image quality.

Image quality assessment of ultra low-dose chest CT using sinogram-affirmed iterative reconstruction.

OBJECTIVES: To assess the image quality of ultra-low-dose computed tomography (ULDCT) using sinogram-affirmed iterative reconstruction (SAFIRE) compared to reduced dose CT (RDCT). METHODS: Eighty-one consecutive patients underwent non-enhanced ULDCT using 80 kVp and 30 mAs and contrast-enhanced RDCT using automated tube potential selection and tube current modulation. CT images were reconstructed with SAFIRE. Image noise and subjective image quality of normal structures and various pulmonary lesions were assessed. RESULTS: The mean effective doses were 0.29 ± 0.03 and 2.88 ± 1.11 mSv for ULDCT and RDCT, respectively. ULDCT had significantly higher noise (p < 0.001). Image quality of five normal structures was diagnostic in 91.1 % of ULDCT and 100 % of RDCT. With ULDCT, the frequencies of non-diagnostic image quality were 2.0 (1/50), 4.6 (13/280), 25.5 (14/55), and 40.0 (8/20)% for BMIs of < 20, 20-25, 25-30, and >30. In the assessment of pulmonary lesions, non-diagnostic image quality was observed for 11.2 % of all lesions, 60.9 % of decreased attenuation (significantly more frequent for upper lung lesions), and 23.5 % of ground-glass nodules. CONCLUSION: ULDCT generates diagnostic images in patients with a BMI ≤25, but is of limited use for lesions with decreased attenuation, ground-glass nodules, or those located in the upper lobe. KEY POINTS: • Iterative reconstruction enables ultra-low-dose CT (ULDCT) with very low radiation doses. • Image quality of ULDCT depends on the patient body mass index (BMI). • Selection of kVp and mAs depends on both BMI and lesion type. • Diagnosis of pulmonary emphysema or ground-glass nodules requires higher radiation doses.

Tuberculous-destroyed lung: cardiovascular CT findings and prognostic imaging factors.

The purpose of this study was to evaluate cardiovascular computed tomography (CT) findings in tuberculous-destroyed lung (TDL) and to correlate these imaging features with survival. CT was assessed for the diameter of the pulmonary artery (dPA) and ascending aorta, the diameters of ventricles, ventricular septal bowing (VSB), extent of TDL, or hypertrophied bronchial artery and others. Seventy-three percent of the TDL patients had a dPA greater than 29 mm. The right ventricle (RV)/left ventricle (LV) ratio in 70% of the patients was greater than 1.0, and VSB was observed in 18%. The RV/LV ratio was the only independent risk factor for poor survival in statistical analysis.

A newly designed Y-shaped covered stent in the palliative treatment of hepatic hilar malignant obstruction: case report.

We report a case in an inoperable patient with the hilar malignant biliary obstruction treated palliatively by the use of a newly designed Y-shaped covered stent without interfering contra-lateral bile duct. We percutaneously inserted a newly designed Y-shaped covered stent into a biliary tree in an inoperable patient with Bismuth Type II cholangiocarcinoma. We checked tubograms, enhanced CT studies, and blood bilirubin levels before, one week after, and at every three month after the stenting, by observing closely the signs of clinical infection as well. The follow-up period was about 12 months. The placement of the Y-shaped covered stent was successful and resulted in adequate biliary drainage in the immediate post-procedural tubogram and in the follow-up abdominal CT. The serum bilirubin levels did not show elevation after the insertion of the Y-shaped covered stent.

Detailed modes of action and biochemical characterization of endo-arabinanase from Bacillus licheniformis DSM13.

An endo-arabinanase (BLABNase) gene from Bacillus licheniformis DSM13 was cloned and expressed in Escherichia coli, and the biochemical properties of its encoded enzyme were characterized. The BLABNase gene consists of a single open reading frame of 987 nucleotides that encodes 328 amino acids with a predicted molecular mass of about 36 kDa. BLABNase exhibited the highest activity against debranched α-(1,5)-arabinan in 50 mM sodium acetate buffer (pH 6.0) at 55°C. Enzymatic characterization revealed that BLABNase hydrolyzes debranched or linear arabinans with a much higher activity than branched arabinan from sugar beet. Enzymatic hydrolysis pattern analyses demonstrated BLABNase to be a typical endo-(1,5)-α-S-arabinanase (EC 3.2.1.99) that randomly cleaves the internal α-(1,5)-linked L-arabinofuranosyl residues of a branchless arabinan backbone to release arabinotriose mainly, although a small amount of arabino-oligosaccharide intermediates is also liberated. Our results indicated that BLABNase acts preferentially along with the oligosaccharides longer than arabinopentaose, thus enabling the enzymatic production of various arabino-oligosaccharides.