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Radiation Oncology Journal Jun 2024This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive...
PURPOSE
This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer.
MATERIALS AND METHODS
Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2-3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded.
RESULTS
The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4-5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates.
CONCLUSION
This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.
PubMed: 38946076
DOI: 10.3857/roj.2024.00080 -
Radiation Oncology Journal Jun 2024To assess risk factors of disease progression after salvage radiation therapy (SRT) with androgen deprivation therapy (ADT) in case of prostate-specific antigen (PSA)...
Analysis of risk factors for disease progression after salvage radiation therapy with androgen deprivation therapy in prostate cancer patients who have prostate-specific antigen persistence after radical prostatectomy.
PURPOSE
To assess risk factors of disease progression after salvage radiation therapy (SRT) with androgen deprivation therapy (ADT) in case of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP).
MATERIALS AND METHODS
We analyzed 57 patients who received SRT with ADT between 2013 and 2019 due to PSA persistence after RP. The endpoint was disease progression defined by biochemical recurrence or clinical recurrence. Age, Pre-RP PSA level, Gleason score, pathologic stage, presence of pelvic lymph node dissection, surgical margins, and PSA at 6-8 weeks after RP were analyzed as predictive factors for disease progression. Kaplan-Meier method and Cox regression models were used for data analysis.
RESULTS
At a median follow-up of 38 months (interquartile range, 26-61), 17 patients had disease progression. Pathologic T stage (pT3b vs. pT3a or lower; hazard ratio [HR] = 9.20; p = 0.035) and PSA level at 6-8 weeks after RP (≥2.04 vs. <2.04 ng/mL; HR = 5.85; p = 0.002) were predictors of disease progression. The 5-year disease progression-free survival rate was 46.7% in pT3b group as compared to 92.9 % in pT3a or lower group, and 18.4% for PSA ≥2.04 ng/mL after RP as compared to 79.2% for PSA <2.04 ng/mL.
CONCLUSION
Pathological T stage (pT3b) and post RP PSA ≥2.04 ng/mL are independent risk factors of disease progression after SRT with ADT in patients with PSA persistence after RP.
PubMed: 38946074
DOI: 10.3857/roj.2023.00962 -
Radiation Oncology Journal Jun 2024Sinonasal malignancies are a rare group of head and neck cancers. We aimed to report the oncological outcomes based on histological types in patients who underwent...
PURPOSE
Sinonasal malignancies are a rare group of head and neck cancers. We aimed to report the oncological outcomes based on histological types in patients who underwent radiotherapy.
MATERIALS AND METHODS
In this single-institution study, we retrospectively retrieved and analyzed data of patients with sinonasal carcinomas who underwent radiotherapy during 2011-2016 as part of their treatment. The 3-year rate of local, regional, and distant recurrences, and overall survival were evaluated according to the histological type.
RESULTS
A total of 28 patients were evaluated in this study, the majority of whom were male (60%). Squamous cell carcinoma (SCC), adenoid cystic carcinoma (ACC), and adenocarcinoma (ADC) were found in 15 patients (53.5%), 8 (28.5%), and 5 (18%), respectively. The highest rates of local and regional recurrences were observed in ACC and SCC, respectively. Distant recurrences were numerically more common in ADC. The 3-year OS was 48%, 50%, and 73% in SCC, ADC, and ACC, respectively.
CONCLUSION
Different histopathologies of sinonasal cancer seem to have different patterns of failure, and this may be considered in the treatment approach.
PubMed: 38946073
DOI: 10.3857/roj.2022.00514 -
Transplantation Jul 2024Donation after circulatory death livers are more susceptible to ischemia/reperfusion injury (IRI) because of a longer period of warm ischemia. Growing evidence now...
BACKGROUND
Donation after circulatory death livers are more susceptible to ischemia/reperfusion injury (IRI) because of a longer period of warm ischemia. Growing evidence now suggests that ferroptosis plays a key regulatory role in the development of IRI, so targeting ferroptosis may be an effective strategy to alleviate IRI in liver transplantation (LT).
METHODS
Using donation after circulatory death LT models in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) models in BRL-3A cells, we tested the effect of the Chinese medicine monomer wogonin on liver IRI and explored the specific mechanism.
RESULTS
Wogonin attenuated liver IRI and increased the survival rate of rats by inhibiting lipid peroxidation and ferroptosis. Mechanistically, arachidonic acid 15-lipoxygenase-1 (ALOX15) and inducible nitric oxide synthase (iNOS) were identified as potential targets of baicalein through bioinformatics analysis combined with in vivo and in vitro experiments. This result was further confirmed by molecular docking and cellular thermal shift assays. Finally, we silenced ALOX15 and iNOS in the OGD/R cell model and found that silencing ALOX15 and iNOS could reproduce the regulatory effect of wogonin and abrogate the regulatory effect of wogonin.
CONCLUSIONS
In brief, this study emphasizes that wogonin exerts a protective effect in liver IRI through the regulation of ALOX15- and iNOS-mediated ferroptosis. ALOX15 and iNOS are potential targets for intervention in IRI induced by LT, and wogonin is a drug candidate for LT patients.
PubMed: 38946036
DOI: 10.1097/TP.0000000000005123 -
Journal of Hepato-biliary-pancreatic... Jun 2024The adjuvant S-1 trial affirmed adjuvant chemotherapy for biliary tract cancer but excluded pT1N0 distal cholangiocarcinoma (DCC) according to the seventh edition of the...
BACKGROUND
The adjuvant S-1 trial affirmed adjuvant chemotherapy for biliary tract cancer but excluded pT1N0 distal cholangiocarcinoma (DCC) according to the seventh edition of the American Joint Committee on Cancer (AJCC) classification. The introduction of tumor depth of invasion (DOI) for T-classification in the eighth edition complicates identifying DCC patients less likely to benefit from adjuvant chemotherapy.
METHODS
Our cohort consisted of 185 patients with DCC who underwent pancreaticoduodenectomy between 2002 and 2019. We compared clinicopathological factors and survival outcomes between pT1N0 patients in the seventh edition and those in the eighth edition. New DOI cutoffs for subdividing pT1N0 (8th edition) patients were evaluated to identify patients less likely to benefit from adjuvant chemotherapy.
RESULTS
Transitioning to the eighth edition increased in pT1N0 cases from eight to 46. The 5-year cumulative recurrence rates of them were 14.3% for the seventh edition and 28.3% for the eighth edition. We proposed a DOI cutoff of <2 mm, at which the 5-year cumulative recurrence rate was 11.5%.
CONCLUSION
The eighth AJCC classification revealed that a significant proportion of pT1N0 DCC patients were at risk for recurrence. A DOI cutoff of <2 mm may be considered to potentially improve patient selection for adjuvant chemotherapy.
PubMed: 38946012
DOI: 10.1002/jhbp.12010 -
Physiologia Plantarum 2024Maize (Zea mays L.) is an important food crop with a wide range of uses in both industry and agriculture. Drought stress during its growth cycle can greatly reduce maize...
Maize (Zea mays L.) is an important food crop with a wide range of uses in both industry and agriculture. Drought stress during its growth cycle can greatly reduce maize crop yield and quality. However, the molecular mechanisms underlying maize responses to drought stress remain unclear. In this work, a WRKY transcription factor-encoding gene, ZmWRKY30, from drought-treated maize leaves was screened out and characterized. ZmWRKY30 gene expression was induced by dehydration treatments. The ZmWRKY30 protein localized to the nucleus and displayed transactivation activity in yeast. Compared with wild-type (WT) plants, Arabidopsis lines overexpressing ZmWRKY30 exhibited a significantly enhanced drought stress tolerance, as evidenced by the improved survival rate, increased antioxidant enzyme activity by superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), elevated proline content, and reduced lipid peroxidation recorded after drought stress treatment. In contrast, the mutator (Mu)-interrupted ZmWRKY30 homozygous mutant (zmwrky30) was more sensitive to drought stress than its null segregant (NS), characterized by the decreased survival rate, reduced antioxidant enzyme activity (SOD, POD, and CAT) and proline content, as well as increased malondialdehyde accumulation. RNA-Seq analysis further revealed that, under drought conditions, the knockout of the ZmWRKY30 gene in maize affected the expression of genes involved in reactive oxygen species (ROS), proline, and myo-inositol metabolism. Meanwhile, the zmwrky30 mutant exhibited significant downregulation of myo-inositol content in leaves under drought stress. Combined, our results suggest that ZmWRKY30 positively regulates maize responses to water scarcity. This work provides potential target genes for the breeding of drought-tolerant maize.
Topics: Zea mays; Reactive Oxygen Species; Droughts; Plant Proteins; Gene Expression Regulation, Plant; Homeostasis; Inositol; Transcription Factors; Arabidopsis; Plants, Genetically Modified; Stress, Physiological; Antioxidants; Plant Leaves; Drought Resistance
PubMed: 38945803
DOI: 10.1111/ppl.14423 -
Clinical Lung Cancer Jun 2024Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significant antitumor activity to advanced non-small-cell lung cancer...
The Design for a Phase II, Randomized, Multicenter Study of CtDNA-Guided Treatment With Furmonertinib Combined Therapy or Furmonertinib Alone for Untreated Advanced EGFR Mutant Non-small-cell Lung Cancer Patients: The FOCUS-C Study.
BACKGROUND
Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significant antitumor activity to advanced non-small-cell lung cancer (NSCLC) patients with classic EGFR mutations. However, EGFR-TKI monotherapy shows poor efficacy in patients whose circulating tumor cell DNA (ctDNA) of EGFR mutations cannot be rapidly cleared.
MATERIALS AND METHODS
As a third-generation TKI, furmonertinib has shown superior antitumor activity and minor toxicity. The FOCUS-C study is a prospective, multicenter, randomized controlled trial (NCT05334277) to explore the efficacy and safety of furmonertinib plus pemetrexed-platinum doublet chemotherapy with or without bevacizumab versus furmonertinib monotherapy in untreated advanced EGFR mutant NSCLC patients without EGFR clearance after the induction therapy of furmonertinib. Patients with EGFR clearance will still receive furmonertinib as Arm A. Patients without ctDNA clearance will be randomized in a 2:2:1 ratio as Arm B1 (furmonertinib), Arm B2 (furmonertinib combined with carboplatin and pemetrexed for 4 cycles, and then furmonertinib and pemetrexed as maintenance therapy) and Arm B3 (Arm B2 regimen plus bevacizumab). The primary endpoint is progression-free survival (PFS) in Arm B2/B1. Secondary endpoints include PFS in Arm B3/B1, PFS in Arm A/B1, PFS in Arm B3/B2, objective response and disease control rate, overall survival and safety in all Arms. Exploratory endpoints are focused on the efficacy based on plasma NGS at different timepoints.
CONCLUSION
This study will evaluate the efficacy and tolerability of furmonertinib plus carboplatin and pemetrexed with or without bevacizumab verses furmonertinib alone in untreated patients with advanced EGFR mutant NSCLC without EGFR clearance.
PubMed: 38945800
DOI: 10.1016/j.cllc.2024.06.002 -
Clinical Colorectal Cancer Jun 2024TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains... (Review)
Review
Oncological Outcomes and Response Rate After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Network Meta-Analysis Comparing Induction vs. Consolidation Chemotherapy vs. Standard Chemoradiation.
TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.
PubMed: 38945765
DOI: 10.1016/j.clcc.2024.06.001 -
International Journal of Biological... Jun 2024Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major...
Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major obstacles to their utilization. To address these issues, we designed a novel dual-network hydrogel microsphere that combines gastric acid resistance with enhanced mucoadhesion, aiming for the targeted delivery of probiotics. Thiolated oxidized guar gum (SOGG) was disulfide-linked to form the first network, and sodium alginate (SA) was cross-linked with Ca to form the second network. Under the protection of the interpenetrating dual network microspheres, a much higher viability of Lactobacillus rhamnosus (LGG) (8.73 log CFU/mL) was achieved in simulated gastric fluid, compared to the zero-survival rate of free LGG. Mucoadhesion tests showed that the adhesion rate of SOGG/SA microspheres to the intestinal mucosa was 1.75 times higher than that of thiol-free microspheres. In vivo studies revealed that LGG-loaded microspheres significantly enhanced intestinal barrier function, remodeled the gut microbiome, and alleviated DSS-induced colitis in mice. Overall, SOGG/SA microspheres provide an effective strategy to the challenges of probiotic reduction in the stomach and rapid expulsion from the intestines, enhancing their health benefits.
PubMed: 38945718
DOI: 10.1016/j.ijbiomac.2024.133395 -
Food Research International (Ottawa,... Aug 2024Infants have digestive environments that are more favorable for microbial proliferation and subsequent endogenous nitrite production than those of adults, but direct...
Infants have digestive environments that are more favorable for microbial proliferation and subsequent endogenous nitrite production than those of adults, but direct evidence of this has been lacking. In this study, we propose a novel epidemiology of infant methemoglobinemia by demonstrating the risk posed by nitrite-producers in the gastrointestinal tract. Nitrite-producers from vegetables (n = 323) were exposed to stress factors of the gastrointestinal environment (gastric pH, intestinal bile salts, anaerobic atmosphere) reflecting 4 different postnatal age periods (Neonate, ≤1 month; Infant A, 1-3 months; Infant B, 3-6 months; Infant C, 6-12 months). "High-risk" strains with a nitrate-to-nitrite conversion rate of ≥1.3 %, the minimum rate corresponding to nitrite overproduction, under the Neonate stress condition were analyzed for intestinal adhesion. Among all the phyla, Pseudomonadota achieved the highest survival (P < 0.05; survival rate of 51.3-71.8 %). Possible cross-protection against bile resistance due to acid shock was observed for all the phyla. All the high-risk strains exhibited moderate autoaggregation (14.0-36.4 %), whereas only a few exhibited satisfactory surface hydrophobicity (>40 %). The Pantoea agglomerans strain strongly adhered to Caco-2 cells (7.4 ± 1.1 %). This study showed the ability of the Pantoea, Enterobacter, and Klebsiella strains to survive under gastrointestinal stress for ≤12 months, to excessively produce nitrite under neonatal stress conditions, and to settle in the human intestine. To our knowledge, this is the first study to reveal the role of the natural flora of vegetables in the epidemiology of infant methemoglobinemia through a multilateral approach.
Topics: Humans; Vegetables; Infant; Methemoglobinemia; Nitrites; Infant, Newborn; Bacterial Adhesion; Bile Acids and Salts; Gastrointestinal Tract; Hydrogen-Ion Concentration; Gastrointestinal Microbiome
PubMed: 38945602
DOI: 10.1016/j.foodres.2024.114582