Purpose: Detection of telomerase reverse transcriptase (TERT) promoter mutations is a crucial process in the integrated diagnosis of glioblastomas. However, the TERT promoter region is difficult to amplify because of its high guanine-cytosine (GC) content (> 80%). This study aimed to analyze the capturing of TERT mutations by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tissues. Materials and Methods: We compared the detection rate of TERT mutations between targeted NGS and Sanger sequencing in 25 cases of isocitrate dehydrgenase (IDH)-wildtype glioblastomas and 10 cases of non-neoplastic gastric tissues. Our customized panel consisted of 232 essential glioma-associated genes. Results: Sanger sequencing detected TERT mutations in 17 out of 25 glioblastomas, but all TERT mutations were missed by targeted NGS. After the manual visualization of the NGS data using an integrative genomics viewer, 16 cases showed a TERT mutation with a very low read depth (mean, 21.59; median, 25), which revealed false-negative results using auto-filtering. We optimized our customized panel by extending the length of oligonucleotide baits and increasing the number of baits spanning the coverage of the TERT promoter, which did not amplify well due to the high GC content. Conclusion Our study confirmed that it is crucial to consider the recognition of molecular bias and to carefully interpret NGS data.

Background: We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. Methods: We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. Results: Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). Conclusion We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.

Background: We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. Methods: We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. Results: Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). Conclusion We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.

Objective: A prospective, assessor-blinded, randomized controlled trial was conducted in patients with chronic low back pain to evaluate the efficacy of portable low power laser therapy (LPLT) and the effect when combined with exercise therapy on pain and functions. Method: 60 patients were recruited and 56 patients, excluding 4 dropouts, were randomly allocated to the LPLT group (Group 1: 19 patients), placebo laser therapy with exercise group (Group 2: 18 patients), and LPLT with exercise group (Group 3: 19 patients). Laser therapy and exercise was performed five times a week for 4 weeks. Visual analogue scale (VAS), Schober test, lumbar range of motion (ROM) measures (flexion, extension and lateral flexion), Oswestry Disability index (ODI) were measured at baseline, at 4 weeks after intervention, and at 6 weeks after 2 weeks of no intervention. Results: Statistically significant improvements were noted in all group by time interaction with respect to all outcome parameters (p＜0.05). All parameters in each group improved not only in the period of treatment (4 weeks), but also in the final evaluation (6 weeks) 2 weeks after the end of treatment. Post-hoc analysis showed statistically significant difference between the LPLT with exercise group and the other groups in all outcome parameters except for the ODI at 4 weeks and at 6 weeks. Conclusion Portable LPLT is effective treatment in reducing pain and improving lumbar ROM and with exercise is more effective than laser or exercise monotherapy for the chronic low back pain patients.

Objective: A prospective, assessor-blinded, randomized controlled trial was conducted in patients with chronic low back pain to evaluate the efficacy of portable low power laser therapy (LPLT) and the effect when combined with exercise therapy on pain and functions. Method: 60 patients were recruited and 56 patients, excluding 4 dropouts, were randomly allocated to the LPLT group (Group 1: 19 patients), placebo laser therapy with exercise group (Group 2: 18 patients), and LPLT with exercise group (Group 3: 19 patients). Laser therapy and exercise was performed five times a week for 4 weeks. Visual analogue scale (VAS), Schober test, lumbar range of motion (ROM) measures (flexion, extension and lateral flexion), Oswestry Disability index (ODI) were measured at baseline, at 4 weeks after intervention, and at 6 weeks after 2 weeks of no intervention. Results: Statistically significant improvements were noted in all group by time interaction with respect to all outcome parameters (p＜0.05). All parameters in each group improved not only in the period of treatment (4 weeks), but also in the final evaluation (6 weeks) 2 weeks after the end of treatment. Post-hoc analysis showed statistically significant difference between the LPLT with exercise group and the other groups in all outcome parameters except for the ODI at 4 weeks and at 6 weeks. Conclusion Portable LPLT is effective treatment in reducing pain and improving lumbar ROM and with exercise is more effective than laser or exercise monotherapy for the chronic low back pain patients.

Purpose: Aster tataricus (AT) is one of the Asteraceae perennial herbs used in traditional Chinese medicine. The herb contains various bioactive substances, such as flavonoids, isoflavonoids, and phenolic compounds in the roots, and exhibits a range of effects including anti-bacterial, anti-oxidant, and anti-inflammatory activities. This study compared the immunomodulatory effects of ethanol and water extracts of whole AT, except the roots, and analyzed the molecular mechanisms for the regulatory effects on cytokine secretion from THP-1 cells. Methods: The effects of AT extract on the cell viability and proliferation of THP-1 cells were analyzed using the Cell Counting Kit-8 method. The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of the AT-treated THP-1 cells were measured using an enzyme-linked immunosorbent assay. The protein levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor kappa B (IκBα), and mitogen-activated protein kinase (MAPK) phosphorylation in the cell lysates were determined by western blotting. Results: The water extract and the ethanol extract of AT did not affect the cell viability, and increased the proliferation of THP-1 cells significantly compared to the vehicle. The water extract increased the secretion of IL-1β from THP-1 cells in a dose-dependent manner, but the ethanol extract had no effect. The expression of COX-2 and iNOS protein and the phosphorylation of MAPK and Akt were induced in AT-treated cells. In addition, IκBα was degraded by AT in a concentration-dependent manner. IL-1β secretion by AT was reduced by extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors, while TNF-α secretion was decreased by inhibitors of ERK, p38 MAPK, and JNK.Interestingly, the p38 MAPK inhibitor increased the production of IL-1β by AT further. Conclusion The water extract of the above-ground parts of AT contains immunomodulatory bioactive substances that stimulate immune cells through the MAPK signaling pathway.

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is performed for single hepatocellular carcinoma (HCC) that are not eligible for surgery or ablation therapy. We investigated the clinical outcomes of patients with a single HCC ≤ 5 cm treated with TACE. METHODS: This study analyzed 175 consecutive patients who underwent TACE as an initial treatment for single HCC ≤ 5 cm. Predictive factors for complete response (CR), recurrence after CR, and overall survival (OS) were evaluated. RESULTS: Total 119 patients (68%) achieved CR after TACE. Tumor size < 3 cm and hepatitis B virus infection were significant predictors of CR (p < 0.05). Recurrent HCC was detected in 73 patients (61.3%) after CR. Age > 65 years and absence of liver cirrhosis were predictive factors for non-recurrence after CR (p < 0.05). The OS for all patients was 80.7 ± 5.6 months, and the 1-, 3-, and 5-year OS rates were 88.1%, 64.8%, and 49.9%, respectively. In multivariate analysis for OS, CR (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.292 to 0.747) and Child class A (HR, 0.390; 95% CI, 0.243 to 0.626) were significant factors. The OS for the CR and Child class A group were 92 and 93.6 months, respectively, and that of the non-CR and Child B, C group were 53.3 and 50.7 months, respectively (p < 0.001). CONCLUSIONS TACE can be a valid treatment in patients with a single HCC ≤ 5 cm not suitable for curative treatment, especially in patients with Child class A and CR after TACE.

BACKGROUND/AIMS: To investigate the predictive factors for complete response (CR) and recurrence after CR in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). METHODS: Among 691 newly diagnosed HCC patients, 287 were treated with TACE as a first therapy. We analyzed the predictive factors for CR, recurrence after CR, and overall survival (OS). RESULTS: Eighty-one patients (28.2%) achieved CR after TACE, and recurrence after CR was detected in 35 patients (43.2%). In multivariate analyses, tumor size (≤5 cm) and single nodularity were predictive factors for CR, with hazard ratios (HRs) of 0.35 (p=0.002) and 0.41 (p<0.001), respectively. Elevated serum α-fetoprotein (AFP) (>20 ng/mL) level and multinodularity exhibited significant relationships with recurrence after CR, with HRs of 2.220 (p=0.026) and 3.887 (p<0.001), respectively. Tumor size (>5 cm), multinodularity, elevated serum AFP (>20 ng/mL) level, Child-Turcotte-Pugh score (B and C), and portal vein thrombosis were significant factors for OS. CONCLUSIONS: In patients treated with TACE as a first therapy, tumor size (≤5 cm) and single nodularity were predictive factors for CR, and multinodularity and elevated serum AFP (>20 ng/mL) levels were predictive factors for recurrence after CR. These factors were also significant for OS.
Carcinoma, Hepatocellular* ; Chemoembolization, Therapeutic ; Humans ; Multivariate Analysis ; Recurrence* ; Venous Thrombosis

No abstract available.
Bendamustine Hydrochloride* ; Cytarabine* ; Drug Therapy* ; Lymphoma*

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
Aged ; Aminopterin/adverse effects/*analogs & derivatives/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bortezomib/adverse effects/*therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Lymphoma, T-Cell, Peripheral/diagnostic imaging/*drug therapy/pathology ; Male ; Neoplasm Recurrence, Local ; Neutropenia/etiology ; Positron Emission Tomography Computed Tomography