ABSTRACT
Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, given their potential as druggable targets. Among 87 patients who underwent curative resection, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype (p = 0.018) and associated with a higher histologic grade (p = 0.008). HER2 did not correlate with clinicopathological features, while c-Met was more common in node-negative groups (p = 0.004) and often co-expressed with EGFR (p = 0.049). EGFR-positive patients had worse disease-free (HR = 2.89; 95% CI, 1.35-6.20; p = 0.061) and overall survival (HR = 6.89; 95% CI, 2.94-16.2; p = 0.026) than EGFR-negative patients. HER2-positive AAC showed a trend towards shorter survival, although not statistically significant, and c-Met had no impact on survival outcomes. In the context of systemic disease, survival outcomes did not vary according to EGFR, HER2, and c-Met expression, but the HER2-positive group showed a trend towards inferior progression-free survival (HR = 1.90; 95% CI, 0.56-6.41; p = 0.166). This study underscores the potential of EGFR, HER2, and c-Met as targets for personalized therapy in AAC, warranting further research to evaluate targeted treatments.
ABSTRACT
Micelle silymarin (MS) is recognized for its diverse range of beneficial properties, which encompass anti-inflammatory, antioxidant, hepatoprotective, and antidiabetic effects. The main objective of this study was to examine the effects of micelle silymarin on the performance, egg quality, blood profile, and absorption rate of silymarin in laying hens. In experiment 1: 288 Hy-Line brown laying hens, 28 wk old, were utilized for this experiment. The hens were randomly allocated into 3 dietary treatment groups, with each group comprising eight replicates of 12 hens, each housed in individual pens with access to feed and water. Over a 12-wk feeding trial, the hens were provided with a basal diet supplemented with different levels of MS: 0, 0.03, and 0.06%. In experiment 2: For this experiment, 192 Hy-Line Brown laying hens were divided into 2 dietary treatment groups, with each group comprising eight replications of 12 hens. The dietary treatments were: TRT1, basal diet + powder silymarin 4%; TRT2, basal diet + MS 4%. From the first experiment, the findings revealed that incorporating micelle silymarin (MS) into the hens' diet significantly increased egg weight at wk 6 (P < 0.05). Similarly, at wk 12 and throughout the entire experiment, significant effects were observed on downgraded egg count, egg production, egg weight, and feed conversion ratio (FCR) (P < 0.05). Moreover, Haugh Units (HU) and albumen height showed a linear improvement (P < 0.05) at wk 4 with MS supplementation. Furthermore, there was a linear increase in egg yolk color, albumen height, and eggshell thickness at wk 8 with MS supplementation (P < 0.05). Furthermore, a layers-fed diet supplemented with MS showed a linear increase (P < 0.05) in HU, egg weight, yolk color, albumen height, eggshell strength, and eggshell thickness in wk 12. Regarding blood profile parameters, the study revealed linear reductions for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) (P < 0.05), whereas there was a tendency for albumin, triglyceride, and cholesterol (P < 0.10). In the second experiment, it was observed that the blood absorption rate of silymarin was higher in TRT2 compared to TRT1 at 2- and 4-h intervals following administration. In summary, increasing MS supplementation in the diet of laying hens enhanced egg production, egg quality, and blood profile. Additionally, silymarin absorption was higher in its micelle form than in its powder form.
ABSTRACT
Achyranthes japonica extract (AJE) is a multifuctional products that express anti-inflammatory, antioxidant and anti-microbial properties. This study was aimed to evaluate the effects of AJE addition to standard and low crude protein (LCP) diet on growth performance, nutrient digestibility, excreta bacterial count, excreta noxious gas emissions, breast meat quality, and organ weight of broiler chicken. A total of 340 one-day-old Ross 308 broilers [initial body weight (BW) of 43.10 ± 1.46 g, 5 replicate cages per treatment, and 17 birds per cage] were randomly distributed into 1 of 4 dietary treatment groups for a 35 day trial. The diets were provided based on three age stage of the broiler. In the starter stage broiler were fed basal diet. Experimental diet were fed to broiler from day 8 to 35. In growing (days 8-21) and finishing (days 22-35) stage broiler were fed: Standard crude protein (SCP) diet and LCP diet with 0.025% and 0.05% of AJE supplementation respectively. Here, the SCP and LCP diets were 21.50% and 20.86% CP during days 8-21 and 20.00% and 19.40% CP during days 22-35, respectively. The SCP diets with 0.025% AJE supplementation resulted in higher (p < 0.5) BW gain (BWG) at finishing stage and a tendency to lower feed conversion ratio and BWG in the overall period compared to LCP diets with or without AJE supplemenation. Moreover, dry matter and nitrogen digestibility were increased with SCP diet along with 0.025% of AJE. No significant difference was found in meat quality parameters except for pH. Interestingly, the NH3 gas emission to the environment was found to be less with different levels of CP and AJE supplementation. Therefore, we concluded that the addition of 0.025% AJE to the SCP diet improved broiler growth performance and nutrient digestibility with low fecal NH3 emissions.
ABSTRACT
Achyranthes japonica extract (AJE) is derived from a medicinal plant Achyranthes japonica, known for its anti-inflammatory, antioxidant, and antimicrobial properties. AJE contains multiple bioactive compounds, including saponins, triterpenoids, phytoecdysteroids, 20-hydroxyecdysone, and inokosterone. The aim of this investigation was to examine the impact of AJE as a phytogenic feed additive on growth performance, nutrient digestibility, excreta microbial count, noxious gas emissions, breast meat quality in broilers. About three hundred and sixty, day-old broilers (Ross 308) were assigned into four treatments (five replication cages/treatment, and 18 birds/cage). Dietary treatments: CON, basal diet; 0.02% AJE, basal diet with 0.02%; 0.04% AJE, basal diet with 0.04% AJE, and 0.06% AJE, basal diet with 0.06% of AJE. Body weight gain increased linearly (p < 0.05) through the inclusion of AJE during days 7 to 21, 21 to 35, as well as the entire experimental period. Besides, feed intake increased (p < 0.05) linearly during days 21 to 35 and the entire experiment with the increased AJE doses in broiler diet. Dry matter digestibility was increased (p < 0.05) linearly along with increasing amounts of AJE. With increasing AJE supplementation, nitrogen and energy utilization tended to improve (p < 0.10). In summary, the addition of AJE in the corn-soybean meal diet led to higher body weight gain and increased feed intake as well as enhanced nutrient digestibility, among them the highest improvement was found in 0.06%-AJE indicating the acceptance of AJE as a phytogenic feed additive.
ABSTRACT
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.
ABSTRACT
In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
ABSTRACT
Introduction: The gastrointestinal tract is integral to defending against external contaminants, featuring a complex array of immunological, physical, chemical, and microbial barriers. Mycotoxins, which are toxic metabolites from fungi, are pervasive in both animal feed and human food, presenting substantial health risks. Methods: This review examines the pharmacological, toxicological, and microbiological impacts of natural products on mycotoxicosis, with a particular focus on the gut-x axis. The analysis synthesizes current understanding and explores the role of natural products rich in polysaccharides, polyphenols, flavonoids, and saponins. Results: The review highlights that mycotoxins can disrupt intestinal integrity, alter inflammatory responses, damage the mucus layer, and disturb the bacterial balance. The toxins' effects are extensive, potentially harming the immune system, liver, kidneys, and skin, and are associated with serious conditions such as cancer, hormonal changes, genetic mutations, bleeding, birth defects, and neurological issues. Natural products have shown potential anticancer, anti-tumor, antioxidant, immunomodulatory, and antitoxic properties. Discussion: The review underscores the emerging therapeutic strategy of targeting gut microbial modulation. It identifies knowledge gaps and suggests future research directions to deepen our understanding of natural products' role in gut-x axis health and to mitigate the global health impact of mycotoxin-induced diseases.
ABSTRACT
This study investigated the impacts of micellar quercetin (MQ) supplementation on growth performance, meat stability, excreta gas emissions, and physiological status. During a 35-day trial, 640 Ross 308 broilers were utilized. These birds were one day old, with an average initial body weight of 43.34 ± 1.43 g. They were randomly distributed across four experimental diets, each consisting of 10 replicate pens with 16 chicks per pen. The diets included the following: control (CON) with 0% micellar quercetin (MQ), TRT1 with 0.025% MQ, TRT2 with 0.050% MQ, and TRT3 with 0.100% MQ. The results indicate that broilers fed diets with increasing levels of MQ exhibited significantly higher body weight gains (BWGs) compared to the control group (p < 0.05). There was a clear linear increase in the breast muscle percentage with higher levels of quercetin supplementation (p < 0.05), while the breast color remained consistent across all groups (p > 0.05). Both cooking loss and drip loss exhibited a linear decrease as MQ levels in the diet increased (p < 0.05). The level of aspartate aminotransferase (AST) tended to decrease with higher MQ levels. Thyroxine (T4) and lymphocyte levels also showed a linear increase with increasing MQ dosage in the diet (p < 0.05). However, no significant effects were observed on nutrient digestibility, gas emissions, or fecal microbial components (Lactobacillus, E. coli, and Salmonella) with higher levels of MQ supplementation (p > 0.05). In conclusion, augmenting quercetin levels in the diet positively influenced the BWG, breast muscle development, and meat quality parameters such as cooking loss and drip loss, with beneficial effects on blood profiles.
ABSTRACT
This study investigated how sucralose influenced rabbit intestine and caecal microbial activity, blood parameters, growth performance, carcass characteristics, and digestibility. In total, 160 5-week-old rabbits from the APRI line weighing 563.29 gm were randomly assigned to four experimental groups with four replicates-5 males and 5 females in each. Four experimental groups were used, as follows: SUC1, SUC2, and SUC3 got 75, 150, and 300 mg of sucralose/kg body weight in water daily, while the control group ate a basal diet without supplements. The results showed that both the control and SUC1 groups significantly (p < 0.05) increased daily weight gain and final body weight. Sucralose addition significantly improved feed conversion ratio (p < 0.05) and decreased daily feed intake (gm/d). The experimental groups do not significantly differ in terms of mortality. Furthermore, nutrient digestibility was not significantly affected by sucralose treatment, with the exception of crud protein digestion, which was significantly reduced (p < 0.05). Additionally, without altering liver or kidney function, sucralose administration dramatically (p < 0.05) decreased blood serum glucose and triglyceride levels while increasing total lipids, cholesterol, and malonaldehyde in comparison to the control group. Furthermore, the addition of sucrose resulted in a significant (p < 0.05) increase in the count of total bacteria, lactobacillus, and Clostridium spp., and a decrease in the count of Escherichia coli. Further analysis using 16S rRNA data revealed that sucralose upregulated the expression of lactobacillus genes but not that of Clostridium or E. Coli bacteria (p < 0.05). Therefore, it could be concluded that sucralose supplementation for rabbits modifies gut microbiota and boosts beneficial bacteria and feed conversion ratios without side effects. Moreover, sucralose could decrease blood glucose and intensify hypercholesterolemia and should be used with caution for human consumption.
ABSTRACT
Background: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC. Methods: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin. Conclusion: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.
Subject(s)
Ataxia Telangiectasia Mutated Proteins , Cisplatin , Cytidine Deaminase , Minor Histocompatibility Antigens , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Ataxia Telangiectasia Mutated Proteins/metabolism , Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors , Cisplatin/pharmacology , Cisplatin/therapeutic use , Cytidine Deaminase/genetics , Cytidine Deaminase/metabolism , Cell Line, Tumor , Male , Minor Histocompatibility Antigens/metabolism , Minor Histocompatibility Antigens/genetics , Middle Aged , Female , Checkpoint Kinase 1/metabolism , Checkpoint Kinase 1/antagonists & inhibitors , Checkpoint Kinase 1/genetics , Apoptosis , Aged , Neoplasm Invasiveness , Cell Proliferation , Cell Survival/drug effectsABSTRACT
The impact of glycine and glutamate, as components of glutathione (GSH) precursors, was studied as a factor in determining the growth rate of weaning pigs, their digestion of nutrient supplements and their blood concentration levels. There were 180 crossbred weaning pigs with an average body weight (BW) of 7.94 ± 1.53 kg (five pigs per pen [two barrows and three gilts]; nine pens per treatment) that were randomly assigned to one of four diets. We used a basal diet as the control, TRT1 as the treatment with 0.10% precursor of GSH, TRT2 as the treatment with 0.20% precursor of GSH and TRT3 as the treatment with 0.30% precursor of GSH. The BW of weaning pigs exhibited a linear increase on days 7 (p < 0.001), 21 (p < 0.001) and 42 (p < 0.009) following the supplementation with the GSH precursor. Supplementation with GSH precursor led to a consistent and gradual increase in average daily gain (ADG) on days 8-21, 22-42 and overall, as indicated by a significant linear trend (p < 0.05). G: F was linearly increased (p < 0.05) on days 22-42 and overall with the increment in the precursor of GSH supplementation. However, GSH precursor supplementation did not have any impact on nutrient digestibility and blood profile in the treatment group. In summary, the administration of GSH precursor improved BW, ADG and G: F ratio while not affecting nutrient digestibility or blood profile.
ABSTRACT
In most current farm operations, lactating sows need to overcome reproductive and environmental stresses that have resulted in poor sow production performance and piglet growth. Therefore, this study aimed to investigate the effects of in-feed supplementation of monosodium glutamate (MSG) in sows during late gestation lactation in regard to litter performance. The study subjects were 12 multi-parity sows (Landrace × Large White), farrowing sows with an average parity of four (three with three parities, seven with four parities, and two with five parities). They were randomly divided into the following two diet groups: the basal diet as a control (CON) group based on corn and soybean meal; and the basal diet + 2% MSG group. The experimental time ranged from 109 days before delivery to 21 days after delivery. There were six sows in each group, and each sow served as the experimental unit. There were no significant differences (p > 0.05) in body weight (BW), back fat (BF) thickness and estrus interval between sows supplemented with 2% MSG in their diets before and after farrowing and during weaning (p > 0.05). However, MSG-treated sows tended to increase BW loss at farrowing more than the CON group (p = 0.093) but lost less weight during lactation than the CON group (p = 0.019). There were no significant differences in the body condition scores (BCSs) and BF loss of the two groups of sows before and after farrowing and at weaning (p > 0.05). There was no significant difference in the weight of newborn piglets between the two groups of sows (p > 0.05). The weaning weight (p = 0.020) and average daily gain (ADG) (p = 0.045) of suckling piglets were higher in the MSG treated group compared to the CON group. The daily milk production of sows in the MSG treatment group was higher compared to the CON group (p = 0.045). The protein concentration of milk at week 3 (p = 0.060) and fat concentration of milk at week 5 (p = 0.095) of the MSG-supplemented sows tended to increase more than the CON group. In summary, the dietary inclusion of MSG supplementation had a beneficial effect on the late gestating sows and their piglet's growth and milk production. Our research has shown that the addition of 2% MSG in late gestation and lactation diet would be beneficial for both sow and piglet production.
ABSTRACT
BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Esophagogastric Junction , Fluorouracil , Leucovorin , Organoplatinum Compounds , Receptor, Fibroblast Growth Factor, Type 2 , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Female , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Leucovorin/administration & dosage , Middle Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Aged , Esophagogastric Junction/pathology , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/administration & dosage , Adult , Double-Blind Method , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Asia, Eastern , Aged, 80 and over , Survival Rate , East Asian PeopleABSTRACT
This study introduces a hydrothermal synthesis method that uses glucose and Cu2+ ions to create a Cu-nanoparticle (NP)-decorated hydrothermal carbonaceous carbon hybrid material (Cu-HTCC). Glucose serves both as a reducing agent, efficiently transforming Cu2+ ions into elemental Cu nanostructures, and as a precursor for HTCC microstructures. An enhanced plasmon-induced electric field resulting from Cu NPs supported on microstructure matrices, coupled with a distinctive localized π-electronic configuration in the hybrid material, as confirmed by X-ray photoelectron spectroscopic analysis, lead to the heightened optical absorption in the visible-near-infrared range. Consequently, flexible nanocomposites of Cu-HTCC/PDMS and Cu-HTCC@PDMS (PDMS = polydimethylsiloxane) are designed as 2 and 3D structures, respectively, that exhibit broad-spectrum solar absorption. These composites promise efficient photo-assisted thermoelectric power generation and water evaporation, demonstrating commendable mechanical stability and flexibility. Notably, the Cu-HTCC@PDMS composite sponge simultaneously exhibits commendable efficiency in both water evaporation (1.47 kg m-2 h-1) and power generation (32.1 mV) under 1 sunlight illumination. These findings unveil new possibilities for innovative photothermal functional materials in diverse solar-driven applications.
ABSTRACT
BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.
Subject(s)
Adenocarcinoma , Ampulla of Vater , Antineoplastic Combined Chemotherapy Protocols , Capecitabine , Common Bile Duct Neoplasms , Oxaliplatin , Humans , Capecitabine/therapeutic use , Capecitabine/administration & dosage , Capecitabine/adverse effects , Male , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Oxaliplatin/adverse effects , Ampulla of Vater/pathology , Female , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aged , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adult , Common Bile Duct Neoplasms/drug therapy , Common Bile Duct Neoplasms/pathology , Common Bile Duct Neoplasms/mortality , Retrospective Studies , Progression-Free Survival , Treatment OutcomeABSTRACT
The close link between intestinal microbiota and bone health ('gut-bone' axis) has recently been revealed: the modulation of the amount and nature of bacteria present in the intestinal tract has an impact on bone health and calcium (Ca) metabolism. Probiotics are known to favorably impact the intestinal microbiota. The objective of this study was to investigate the effect of Pediococcus acidilactici CNCM I-4622 (PA) on laying performance, egg/eggshell quality, Ca metabolism and bone mineralization and resistance in relatively old layers (50 wks old at the beginning of the experiment) during 14 weeks. 480 Hy Line brown layers were divided into 2 groups (CON and PA: 3 layers/rep, 80 rep/group) and fed with a diet formulated to be suboptimal in calcium (Ca) and phosphorus (P) (- 10% of the requirements). The total egg weight was improved by 1.1% overall with PA, related to an improvement of the weight of marketable eggs (+ 0.9%). PA induced a decreased % of downgraded eggs, mainly broken eggs (- 0.4 pts) and FCR improvement (- 0.8% for all eggs, - 0.9% for marketable eggs). PA also led to higher Haugh units (HU: + 7.4%). PA tended to decrease crypt depth after the 14 weeks of supplementation period in the jejunum (- 25.2%) and ileum (- 17.6%). As a consequence, the VH/CD ratio appeared increased by PA at the end of the trial in the jejunum (+ 63.0%) and ileum (+ 48.0%). Ca and P retention were increased by 4 pts following PA supplementation, translating into increased bone hardness (+ 19%), bone cohesiveness (+ 43%) and bone Ca & P (+ 1 pt) for PA-supplemented layers. Blood Ca and P were respectively improved by 5% and 12% with PA. In addition, blood calcitriol and osteocalcin concentrations were respectively improved by + 83% and + 3% in PA group at the end of the trial, compared to CON group. There was no difference between the 2 groups for ALP (alkaline phosphatase) and PTH (parathyroid hormone). PA significantly decreased the expression of the following genes: occludin in the small intestine, calbindin 1 in the ovarian tissue and actin B in the bone. PA therefore improved zootechnical performance of these relatively old layers, and egg quality. The parallel increase in Ca and P in the blood and in the bone following PA supplementation suggests an improvement of the mineral supply for eggshell formation without impacting bone integrity, and even increasing bone resistance.
Subject(s)
Calcium , Chickens , Dietary Supplements , Pediococcus acidilactici , Phosphorus , Probiotics , Animals , Probiotics/administration & dosage , Pediococcus acidilactici/metabolism , Phosphorus/metabolism , Calcium/metabolism , Female , Animal Feed , Eggs , Oviposition/drug effects , Gastrointestinal MicrobiomeABSTRACT
BACKGROUND: Optimal gut health is important to maximize growth performance and feed efficiency in broiler chickens. A total of 1,365 one-day-old male Ross 308 broiler chickens were randomly divided into 5 treatments groups with 21 replicates, 13 birds per replicate. The present research investigated effects of microbial muramidase or a precision glycan alone or in combination on growth performance, apparent total tract digestibility, total blood carotenoid content, intestinal villus length, meat quality and gut microbiota in broiler chickens. Treatments included: NC: negative control (basal diet group); PC: positive control (basal diet + 0.02% probiotics); MR: basal diet + 0.035% microbial muramidase; PG: basal diet + 0.1% precision glycan; and MRPG: basal diet + 0.025% MR + 0.1% PG, respectively. RESULTS: MRPG group increased the body weight gain and feed intake (P < 0.05) compared with NC group. Moreover, it significantly increased total serum carotenoid (P < 0.05) and MRPG altered the microbial diversity in ileum contents. The MRPG treatment group increased the abundance of the phylum Firmicutes, and family Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Lactobacillaceae, Peptostreptococcaceae and decreased the abundance of the phylum Campilobacterota, Bacteroidota and family Bacteroidaceae. Compared with the NC group, the chickens fed MRPG showed significantly increased in duodenum villus length at end the trial. CONCLUSION: In this study, overall results showed that the synergetic effects of MR and PG showed enhancing growth performance, total serum carotenoid level and altering gut microbiota composition of broilers. The current research indicates that co-supplementation of MR and PG in broiler diets enhances intestinal health, consequently leading to an increased broiler production.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77 advanced PDAC patients via ELISA, the research determined optimal cutoff values for IL-6 and the IL-6:sIL-6Rα ratio using receiver operating characteristic curve analysis, which then facilitated the division of patients into low and high IL-6 groups, showing significantly different survival outcomes. Notably, high IL-6 levels correlated with adverse features such as poorly differentiated histology, higher tumor burden, and low albumin levels, indicating a stronger likelihood of poorer prognosis. With a median follow-up of 9.28 months, patients with lower IL-6 levels experienced markedly better median overall survival and progression-free survival than those with higher levels, underscoring IL-6's role in predicting disease prognosis. Multivariate analysis further confirmed IL-6 levels, alongside older age, and elevated neutrophil-to-lymphocyte ratio, as predictors of worse outcomes, suggesting that IL-6 could be a critical biomarker for tailoring treatment strategies in advanced PDAC, warranting further investigation into its role in systemic inflammation and the tumor microenvironment.
ABSTRACT
This study investigated the impact of clay mineral 'illite' (IL) on the growth performance, apparent total tract digestibility, and meat-carcass grade quality in growing-finishing pigs. One hundred fifty pigs were divided into two groups with fifteen pens/group and five pigs/pen, a control group that was fed with a corn-soybean meal-based diet and IL treated group were fed a meal-based diet supplemented with 0.5% IL. Compared to the control, IL supplementation increased average daily feed intake (ADFI) and reduce gain to feed ratio (G:F) in the pigs during days 43 to 70 and 99 to 126 and increased dry matter during days 42 and 126, and backfat thickness on day 98 (p < 0.05). The drip loss was reduced on day 7, meat firmness tended to increase with dietary IL supplementation. In summary, dietary 0.5% IL supplementation improved ADFI, nutrient utilization of dry matter, and firmness and reduced G:F and drip loss of growing-finishing pigs.
ABSTRACT
This study was done to investigate the effects of the incorporation of Achyranthes japonica extracts (AJE) in diet on the production parameters of growing pigs. Exp 1: Total, 105 crossbred pigs (average body weight: 24.47 ± 2.46 kg) were used in a 6-week feeding trial. Pigs (seven replicates, five pigs per pen) were allotted randomly to three treatments. Dietary treatments: CON (basal diet); basal diet with 0.025% AJE, and basal diet + 0.050% AJE). Growth performance, nutrient digestibility, fecal microbial count, and fecal noxious gas were assessed in this study. Average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) were not affected by the addition of up to 0.05% AJE. In the case of apparent total tract digestibility (ATTD), dry matter (DM), nitrogen (N), and digestible energy (DE) were not changed in 3rd and 6th weeks of the feeding trial through the addition of AJE up to 0.05% in the growing pig diet. In microbial count, Lactobacillus and Escherichia coli count at 3rd and 6th week was similar in all the treatment diets. The inclusion of AJE at levels up to 0.05% in growing pig diet had no effect on the production of NH3, H2S, acetic acid, and CO2 in the feces. After ending the Exp 1, a total of nine pigs were divided into three treatment groups. Treatment diets were included, TRT1, basal diet + powder quercetin 30 g; TRT2, basal diet + powder quercetin 150 g; TRT3, basal diet + powder quercetin 300g. Rate of absorption in blood was increased with the higher dose of quercetin. The results suggested incorporation of AJE up to 0.05% has no significant effect on ADG, ADFI, and G:F, as well as DM, N, and DE digestibility, fecal microbial count, and fecal noxious gas emission in growing pigs, even though no negative effect was found.