Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study.

OBJECTIVES: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. MATERIALS AND METHODS: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. RESULTS: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). CONCLUSION: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.

Surface-Engineered Titanium with Nanoceria to Enhance Soft Tissue Integration Via Reactive Oxygen Species Modulation and Nanotopographical Sensing.

The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-ß signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

Comparative Study on the Immunogenicity of COVID-19 mRNA Vaccines in Patients Receiving Adjuvant and Palliative Chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. RESULTS: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. CONCLUSIONS: ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent and/or metastatic HNSCC. METHODS: In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti-PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment. RESULTS: Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths. CONCLUSION: To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.

Treatment Patterns and Prognosis of Palliative Chemotherapy Combined With Targeting Agents in Patients With Unresectable Metastatic Colorectal Cancer: CHOICE, A Multicenter Longitudinal Observational Study.

BACKGROUND/AIM: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents. PATIENTS AND METHODS: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors. RESULTS: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC. CONCLUSION: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors.

Effects of environmental factors and intraspecific niche overlap on the body and ecological characteristics of red-tongued pit vipers (Gloydius ussuriensis).

The body condition of a snake species provides important physiological, morphological, and ecological information that elucidates its habits, life cycle, and competitive relationships. We measured the body size and condition of the wild Gloydius ussuriensis population in South Korea from 2018 to 2022, analyzed the degree of intraspecific niche overlap, and identified the geographic and climatic factors affecting their body condition. We found that the females were longer than the males. The body condition index (BCI) of G. ussuriensis differed depending on sex and season; the BCI of the females and males was highest in August and October, respectively. Environmental factors related to altitude and temperature affected the body condition of G. ussuriensis; BCI increased as the mean annual temperature and winter temperature increased; however, it increased when the annual temperature range decreased. The mean Pinaka index was 0.96, indicating a high degree of niche overlap; however, the niche overlap among the neonates was less than that among the adults and juveniles. To elucidate the causes of niche overlap and mechanisms behind the intraspecific competition among G. ussuriensis individuals, the habitat and utilization of food resources at different development stages of G. ussuriensis should be further investigated.

Nucleoredoxin gene SINRX1 negatively regulates tomato immunity by activating SA signaling pathway.

The tomato (Solanum lycopersicum) is widely consumed globally and renowned for its health benefits, including the reduction of cardiovascular disease and prostate cancer risk. However, tomato production faces significant challenges, particularly due to various biotic stresses such as fungi, bacteria, and viruses. To address this challenges, we employed the CRISPR/Cas9 system to modify the tomato NUCLEOREDOXIN (SlNRX) genes (SlNRX1 and SlNRX2) belonging to the nucleocytoplasmic THIOREDOXIN subfamily. CRISPR/Cas9-mediated mutations in SlNRX1 (slnrx1) plants exhibited resistance against bacterial leaf pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326, as well as the fungal pathogen Alternaria brassicicola. However, the slnrx2 plants did not display resistance. Notably, the slnrx1 demonstrated elevated levels of endogenous salicylic acid (SA) and reduced levels of jasmonic acid after Psm infection, in comparison to both wild-type (WT) and slnrx2 plants. Furthermore, transcriptional analysis revealed that genes involved in SA biosynthesis, such as ISOCHORISMATE SYNTHASE 1 (SlICS1) and ENHANCED DISEASE SUSCEPTIBILITY 5 (SlEDS5), were upregulated in slnrx1 compared to WT plants. In addition, a key regulator of systemic acquired resistance, PATHOGENESIS-RELATED 1 (PR1), exhibited increased expression in slnrx1 compared to WT. These findings suggest that SlNRX1 acts as a negative regulator of plant immunity, facilitating infection by the Psm pathogen through interference with the phytohormone SA signaling pathway. Thus, targeted mutagenesis of SlNRX1 is a promising genetic means to enhance biotic stress resistance in crop breeding.

Curative resection of leiomyosarcoma of the descending colon with metachronous liver metastasis: A case report.

BACKGROUND: Leiomyosarcoma (LMS) has a poor prognosis and rarely originates from the colon. If resection is possible, surgery is the first treatment most commonly considered. Unfortunately, no standard treatment exists for hepatic metastasis of LMS; although, several treatments, such as chemotherapy, radiotherapy, and surgery, have been used. Subsequently, the management of liver metastases remains controversial. CASE SUMMARY: We present a rare case of metachronous liver metastasis in a patient with LMS originating from the descending colon. A 38-year-old man initially reported abdominal pain and diarrhea over the previous two months. Colonoscopy revealed a 4-cm diameter mass in the descending colon, 40 cm from the anal verge. Computed tomography revealed intussusception of the descending colon due to the 4-cm mass. The patient underwent a left hemicolectomy. Immunohistochemical analysis of the tumor revealed that it was positive for smooth muscle actin and desmin, and negative for cluster of differentiation 34 (CD34), CD117, and discovered on gastrointestinal stromal tumor (GIST)-1, which are characteristic of gastrointestinal LMS. A single liver metastasis developed 11 mo post-operatively; the patient subsequently underwent curative resection thereof. The patient remained disease-free after six cycles of adjuvant chemotherapy (doxorubicin and ifosfamide), and 40 and 52 mo after liver resection and primary surgery, respectively. Similar cases were obtained from a search of Embase, PubMed, MEDLINE, and Google Scholar. CONCLUSION: Early diagnosis and surgical resection may be the only potential curative options for liver metastasis of gastrointestinal LMS.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Status of Using Complementary and Alternative Medicine among Patients with Cancer in Korea: an Online Survey of Online Cancer Support Groups (KCSG PC21-20).

PURPOSE: An increasing number of patients with cancers are interested in complementary and alternative medicine (CAM), which lacks scientific evidence. This study aimed to determine how CAM was used and how media affected patients in online cancer support groups (OCSG). Materials and Methods: Between August 18 and September 12, 2021, an online survey was conducted among the members of OCSG. The survey consisted of five parts: baseline characteristics, attitudes toward and experience with CAM, source of information and reliabilities, experience with anthelmintics, and online health information literacy and usage. RESULTS: Among the 644 responders, a total of 221 patients with cancer completed the survey, and 78.2% (173/221) used CAM. The users' median age was 52 years; 46.8% were males, and 43.9% had metastatic disease. Fifty-three CAM users (30.6%) discussed their physicians about CAM. In addition, 16.2% (28/173) of CAM users had the experience of anthelmintics. The use of anthelmintics in patients with cancers was associated with younger age (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84 to 0.95), metastatic disease (OR, 10.88; 95% CI, 3.39 to 34.86), previous exposure to CAM information (OR, 5.57; 95% CI, 1.01 to 30.72), experience with more types of CAM (OR, 1.98; 95% CI, 1.29 to 3.05), and side effects (OR, 5.10; 95% CI 1.46 to 17.75). CONCLUSION: Use of anthelmintics, a CAM of which information is widespread online, is affected by several factors. This study will provide essential information for developing a CAM management strategy in this digital age.

Correction: Understanding the Social Mechanism of Cancer Misinformation Spread on YouTube and Lessons Learned: Infodemiological Study.

[This corrects the article DOI: 10.2196/39571.].

Study on the use of Nanostring nCounter to analyze RNA extracted from formalin-fixed-paraffin-embedded and fresh frozen bladder cancer tissues.

Formalin-fixed paraffin-embedded (FFPE) tissue is the most common source of archived material for genomic medicine. However, FFPE tissue is suboptimal for high-throughput analyses, such as RNA sequencing, because the quality of nucleic acids in FFPE tissues is low. We compared RNA-seq with the nCounter system to evaluate use of FFPE tissue for genomic medicine. Twelve fresh frozen bladder cancer samples were analyzed by both RNA sequencing and nCounter, and matched FFPE samples, by nCounter. Gene-expression values obtained by these two platforms were compared by calculating Pearson correlation coefficients for each sample (across the set of matched genes) and for each matched gene (across the set of samples). For each sample, gene-expression levels measured by RNA sequencing highly correlated with those measured by nCounter (all Pearson's R > 0.8, P < 0.0001), as seen by hierarchical clustering. RNA sequencing results for fresh frozen tissues positively correlated with nCounter results for FFPE tissues (R ranged from 0.675 to 0.873, all P < 0.0001). Correlation and hierarchical-clustering analyses of nCounter data from the two specimens demonstrated a strong positive correlation between each group (R ranged from 0.779 to 0.977, all P < 0.0001). Our findings suggest that the nCounter system is useful for assaying archived-FFPE samples and that the gene-expression signatures obtained from FFPE samples represent those from fresh frozen tissues.

Understanding the Social Mechanism of Cancer Misinformation Spread on YouTube and Lessons Learned: Infodemiological Study.

BACKGROUND: A knowledge gap exists between the list of required actions and the action plan for countering cancer misinformation on social media. Little attention has been paid to a social media strategy for disseminating factual information while also disrupting misinformation on social media networks. OBJECTIVE: The aim of this study was to, first, identify the spread structure of cancer misinformation on YouTube. We asked the question, "How do YouTube videos play an important role in spreading information about the self-administration of anthelmintics for dogs as a cancer medicine for humans?" Second, the study aimed to suggest an action strategy for disrupting misinformation diffusion on YouTube by exploiting the network logic of YouTube information flow and the recommendation system. We asked the question, "What would be a feasible and effective strategy to block cancer misinformation diffusion on YouTube?" METHODS: The study used the YouTube case of the self-administration of anthelmintics for dogs as an alternative cancer medicine in South Korea. We gathered Korean YouTube videos about the self-administration of fenbendazole. Using the YouTube application programming interface for the query "fenbendazole," 702 videos from 227 channels were compiled. Then, videos with at least 50,000 views, uploaded between September 2019 and September 2020, were selected from the collection, resulting in 90 videos. Finally, 10 recommended videos for each of the 90 videos were compiled, totaling 573 videos. Social network visualization for the recommended videos was used to identify three intervention strategies for disrupting the YouTube misinformation network. RESULTS: The study found evidence of complex contagion by human and machine recommendation systems. By exposing stakeholders to multiple information sources on fenbendazole self-administration and by linking them through a recommendation algorithm, YouTube has become the perfect infrastructure for reinforcing the belief that fenbendazole can cure cancer, despite government warnings about the risks and dangers of self-administration. CONCLUSIONS: Health authorities should upload pertinent information through multiple channels and should exploit the existing YouTube recommendation algorithm to disrupt the misinformation network. Considering the viewing habits of patients and caregivers, the direct use of YouTube hospital channels is more effective than the indirect use of YouTube news media channels or government channels that report public announcements and statements. Reinforcing through multiple channels is the key.

Utility of a Molecular Signature for Predicting Recurrence and Progression in Non-Muscle-Invasive Bladder Cancer Patients: Comparison with the EORTC, CUETO and 2021 EAU Risk Groups.

To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed. Cox regression analyses showed that the MSP888 was an independent predictor of NMIBC progression in the CBNUH cohort (p = 0.043). Particularly in patients without an intravesical BCG immunotherapy, MSP888 significantly linked with risk of disease recurrence and progression (both p < 0.05). However, the EORTC, CUETO and 2021 EAU risk scores showed disappointing results with respect to estimating the NMIBC prognosis. In the UROMOL cohort, the MSP888, Lund and UROMOL subtypes demonstrated a similar capacity to predict NMIBC progression (all p < 0.05). Conclusively, the MSP888 is favorable for stratifying patients to facilitate optimal treatment.

The thiol-reductase activity of YUCCA6 enhances nickel heavy metal stress tolerance in Arabidopsis.

Anthropogenic activities cause the leaching of heavy metals into groundwater and their accumulation in soil. Excess levels of heavy metals cause toxicity in plants, inducing the production of reactive oxygen species (ROS) and possible death caused by the resulting oxidative stress. Heavy metal stresses repress auxin biosynthesis and transport, inhibiting plant growth. Here, we investigated whether nickel (Ni) heavy metal toxicity is reduced by exogenous auxin application and whether Ni stress tolerance in Arabidopsis thaliana is mediated by the bifunctional enzyme YUCCA6 (YUC6), which functions as an auxin biosynthetic enzyme and a thiol-reductase (TR). We found that an application of up to 1 µM exogenous indole-3-acetic acid (IAA) reduces Ni stress toxicity. yuc6-1D, a dominant mutant of YUC6 with high auxin levels, was more tolerant of Ni stress than wild-type (WT) plants, despite absorbing significantly more Ni. Treatments of WT plants with YUCASIN, a specific inhibitor of YUC-mediated auxin biosynthesis, increased Ni toxicity; however yuc6-1D was not affected by YUCASIN and remained tolerant of Ni stress. This suggests that rather than the elevated IAA levels in yuc6-1D, the TR activity of YUC6 might be critical for Ni stress tolerance. The loss of TR activity in YUC6 caused by the point-mutation of Cys85 abolished the YUC6-mediated Ni stress tolerance. We also found that the Ni stress-induced ROS accumulation was inhibited in yuc6-1D plants, which consequently also showed reduced oxidative damage. An enzymatic assay and transcriptional analysis revealed that the peroxidase activity and transcription of PEROXIREDOXIN Q were enhanced by Ni stress to a greater level in yuc6-1D than in the WT. These findings imply that despite the need to maintain endogenous IAA levels for basal Ni stress tolerance, the TR activity of YUC6, not the elevated IAA levels, plays the predominant role inNi stress tolerance by lowering Ni-induced oxidative stress.

Very severe immune aplastic anemia after mRNA vaccination against COVID-19 responds well to immunosuppressive therapy: clinical characteristics and comparison to previous reports.

OBJECTIVE: Various hematologic side effects of the Coronavirus Disease 2019 (COVID-19) vaccination has been reported, and most of them are thought to be related to autoimmune pathways. To the best of our knowledge, only few cases of post-COVID-19 vaccination aplastic anemia (AA) have been reported and there is no reported Korean case of COVID-19 vaccine-induced AA yet. We present a case of severe immune-mediated AA that developed after the administration of a messenger ribonucleic acid (mRNA) gene-based spike protein vaccine against COVID-19, which responded well to immunosuppressive therapy, and discuss the probable pathogenesis of AA and the implication of vaccination along with a comparison of previous cases reported. METHODS: A 53-year-old Korean man developed sudden pancytopenia three months after COVID-19 vaccination. To evaluate the cause of pancytopenia, a bone marrow study was performed. RESULTS: A diagnosis of AA was made through the bone marrow study and he received triple immunosuppressive therapy (IST). After triple IST for five months, his blood cell count was improved and maintained without transfusion and his follow-up bone marrow examination showed improved cellularity. CONCLUSION: COVID-19 vaccine might be associated with the development of immune-mediated AA. Prompt hematologic evaluation should be performed when there are symptoms or signs suggestive of cytopenia after COVID-19 vaccination. Although the clinical outcome of post-vaccination AA varies, a good prognosis can be possible for patients with COVID-19 vaccination-induced AA.

Association between Timing and Duration of Adjuvant Chemotherapy and Colorectal Cancer Survival in Korea, 2011-2014: A Nationwide Study based on the Health Insurance Review and Assessment Service Database.

Background: Population-based analyses of the treatment outcomes of colorectal cancer (CRC) in Asian countries are limited. Therefore, we conducted a nationwide study to assess the relationship between the timing and duration of adjuvant chemotherapy (AC) and survival in patients with CRC in South Korea. Methods: Data on AC from the Health Insurance Review and Assessment Service Database (HIRA) were analyzed, and the survival of patients who underwent curative-intent surgical resection for CRC between 2011 and 2014 was investigated. Results: From the HIRA data, 45,992 patients with stage II-III CRC were identified. Chemotherapy regimens were administered as follows: 10,640 (23.3%) received 5-fluorouracil and leucovorin/capecitabine (FL/CAP), 13,083 (28.7%) received FL/CAP plus oxaliplatin (FOLFOX/CAPOX), 299 (0.7%) received uracil and tegafur/doxifluridine (UFT/D), and 21,570 (47.3%) underwent surgery alone. Patients who did not receive AC had worse survival than those who received AC in both the colon and rectum groups (HR, 1.96, 95% CI, 1.85-2.07 and HR, 2.18, 95% CI, 2.01-2.37, respectively). Regarding patients with stage II-III CRC, AC initiation ≥ 2 months after surgery was associated with a significant decrease in overall survival (OS) (FL/CAP: HR, 1.82; 95% CI, 1.53-2.17 and FOLFOX/CAPOX: HR, 2.92; 95% CI, 2.47-3.45); however, the effects of UFT/D regimens were not statistically significant. For patients with stage II-III colon cancer, AC <3 months had lower OS (FL/CAP: HR, 3.72, 95% CI, 2.80-4.94; FOLFOX/CAPOX: HR, 2.15, 95% CI, 1.87-2.47; and UFT/D: HR, 1.74, 95% CI, 0.56-5.41). In terms of patients with stage II-III rectal cancer, AC <3 months, regardless of chemotherapy regimens, had a significant lower survival (FL/CAP: HR, 1.91, 95% CI, 1.66-2.20; FOLFOX/CAPOX: HR, 2.20, 95% CI, 1.75-2.77; and UFT/D: HR, 3.71, 95% CI, 1.45-9.44). Conclusions: Postoperative time to initiation and duration of AC were associated with survival. Based on our results, initiating AC within 2 months after surgery and administering AC for >3 months can potentially have an OS benefit in patients with stage II-III CRC.