Introduction

There is currently lack of published data on the use of ustekinumab (UST) in routine care setting in Greece. REASSURE study aimed to generate real-world evidence (RWE) on treatment persistence, and patient-reported outcomes (PROs) in patients with Crohn’s Disease (CD).

Aims & Methods

This was an observational, prospective study of adult (18-80 years old) patients with confirmed diagnosis of CD, who commenced therapy with UST as 1^st, 2^nd, or 3rd line biologic treatment, according to physician’s decision, local standards of clinical practice and as per label indication. Data were collected by routine assessments, including Harvey-Bradshaw Index (HBI), and PROs at baseline (start of UST) and follow-up visits every 6-months. Last visit was done at month 24 (±2 months) or at treatment discontinuation (whichever occurred first). Drug persistence, disease activity and safety outcomes over the 24-month observation period are presented herein.

Results

A total of 169 eligible patients were enrolled in 19 Gastroenterology Clinics in Greece between April 2019 and February 2021. At baseline, median age was 45.0 years, 50.9% (86/169) of patients were females, 43.4% (72/166) were employed, and 68.5% (113/165) were former or current smokers. UST was the 1st, 2^nd, and 3rd biologic treatment in 35.5% (60/169), 35.5% (60/169), and 29.0% (49/169) of patients, respectively. The median duration of study participation was 23.9 months (median number of injections received: 13.0). At 24 months, 21.9% (37/169) of patients had discontinued UST after a mean of 10.2 months due to lack/loss of response (15/37), safety issues (10/37), lost at follow-up (6/37), patient’s wish (2/37), death (2/37; both unrelated to UST), pregnancy (1/37) and patient issues (1/37). The Kaplan-Meier (KM)-estimated median drug survival (i.e., time to treatment discontinuation) was not reached in the overall population or subgroups by treatment line, with no statistically significant differences in the risk of UST discontinuation between subgroups of interest [2L vs 1L: hazard ratio (HR)=1.07, 95% confidence interval (CI)=0.48-2.39; 3L vs 1L: HR=1.54, 95% CI=0.70-3.40; 3L vs 2L: HR=1.42, 95% CI=0.65-3.11). The KM-estimated UST treatment-persistence rates for the overall population s were 86.7%, 80.5%, and 78.0%, at 12-, 18-, and 24-months, respectively. The baseline median total ΗΒΙ (8.0) significantly improved (P<0.001) at 12, 18, and 24 months, with a median 4-point reduction at each timepoint, among paired observations. Significant improvements were also noted based on imputed data and in the subgroups per treatment line. The adverse event (AE), serious AE, and UST-related AE rates were 63.9% (108/169), 18.9% (32/169), and 19.5% (33/169), respectively. Each UST-related AE was reported in <4.0% of the patients. Further details on baseline characteristics, 12/18/24-month outcomes, and UST-related AEs are presented in Table 1.

Conclusion

Our data provide RWE for high persistence rate of treatment with UST in our series with Greek patients with CD. Treatment with UST demonstrated a highly favorable effect on disease activity, in combination with a predictable safety profile.

Disclosure

Disclosure: This study was sponsored by Janssen - Cilag, Greece.

Giorgos Bamias Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma, Adacyte Therapeutics, Amgen, Ferring, Cooper, BMS; Funding (Grants/Honoraria): Pfizer, Takeda, Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda, Janssen.
Gerassimos J. Mantzaris has received consultant and/or speaker fees from AbbVie, MSD, Celtrion,Ferring, Aenorasis, Janssen, Pfizer, Takeda, Falk Pharma, and Vianex and research support from AbbVie, Ferring, MSD, and Vianex
Maria Tzouvala has received clinical research funding from Janssen-Cilag Pharmaceuticals SACI, Takeda HELLAS SA, AbbVie Pharmaceuticals S.A. Consulting and/or speaking fees MSD Sharp& Dohme, Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen. Advisory boards: Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen
Dimitrios Christodoulou has received consulting and speaking fees for Janssen, MSD, Galenica. Advisory Board for Galenica
Ioannis Koutroubakis has received clinical research funding: Abbvie, Faran, Ferring, Pfizer, Viatris, Vianex, Vifor, Unipharma. Consulting and/or speaking fees Abbvie, Genesis, Janssen, MSD, Takeda, Vianex. Advisory boards: Abbvie, Janssen, MSD, Pfizer, Takeda, Vianex
Christos Liatsos has received clinical research funding from: Janssen, and consulting and/or speaking fees from: MSD, Pfizer, Boston SCI, Amgen, Galenica.
Georgios Papatheodoridis Clinical research funding: Abbvie, Gilead, Takeda, Vianex. Consulting and/or speaking fees: Abbvie, Astra-Zeneca, BioARS Therapeutics, Elpen, Genesis, Gilead, GlaxoSmithKline, Ipsen, Novo Nordisk, Roche, Sobi. Advisory boards: Abbvie, Astra-Zeneca, Albireo, Amgen, Galenica, Genesis, Gilead, GlaxoSmithKline, Ipsen, Janssen, Novo Nordisk, Roche, Takeda
Dr Katsanos Konstantinos received honoraria for consulting services (educational services, scientific articles, participation in Advisory Boards, clinical trials, lecture fees, other) from the companies as follows:AbbVie, AMGEN, ENORASIS, Epsilon Health, Ferring, Genesis, Grifols S.A., JANSSEN, MSD, Mylan, Shire and Takeda.
Evanthia Zampeli has received clinical research funding: Janssen, TAKEDA, ABBVIE. Consulting and/or speaking fees: Janssen, TAKEDA, BMS, AMGEN, MYLAN. Advisory boards: BMS, GALENICA
Georgios Germanidis has received clinical research funding from Janssen.
Konstantinos Soufleris Consulting and/or speaking fees: AbbVie, Janssen, MSD, Pfizer, Takeda. Clinical research funding:Pfizer. Advisory board: BMS, Galenica.
Matina-Lydia Chatzinikolaou has received consulting fees from Abbvie, Takeda, Amgen, Ferring, Janssen
George Kokkonis has received clinical Research funding from Janssen and speaking fees from Janssen and Amgen
Alexandros Boubonaris has served as advisory board member for Amgen, Takeda
Marios Giakoumis has received clinical research funding from Janssen
Artemis Trikola has received clinical research funding from Janssen
George Michalopoulos has received speaker fees : Takeda, MSD, , Abbvie, Jannsen, Pfizer, Amgen
Vasileios Delis, Konstantina Paraskeva, Theodosios Sdonas, Athanasia Tasovasili, Evgenia Papathanasiou, Maria Palatianou, Andreaddds Nakos, Nikoletta Mathou, George Kalopitas, Panagiotis Giannelis, Kalliopi Foteinogiannopoulou, Konstantina Chalakatevaki, Eleni Beka, Chara Lamouri, Eleftheria Giannakoulopoulou have no conflicts to disclose.
Konstantinos Thomopoulos, Stergios Vradelis, Andreas Protopapas, Ioannis Pachiadakis, Ioannis Goulis, Pantelis Karatzas, George Theocharis, George Tribonias, Angeliki Machaira, Nikolaos Kyriakos, Adonis Protopapas, Konstantinos Fasoulas, Eleni Orfanoudaki and Charilaos Taloumtzis have not disclosed any conflicts.
Spyridon Michopoulos has received clinical research funding from Janssen, Takeda, BMS, consulting and/or speaking fees from Takeda, and has served as advisory board member for Takeda.
Christos Gkamaloutsos, Ioannis Kanistras and Aikaterini Mpartsea are employees of Janssen - Cilag, Greece.

Introduction

Budesonide orodispersible tablet (BOT) is the only approved topical steroid available in Europe for the induction and maintenance of remission in patients with eosinophilic esophagitis (EoE). Available randomized controlled trials have demonstrated that, following induction of histological remission with BOT 1mg twice daily (bid), patients can be maintained in remission with BOT 0.5mg bid. It is currently unknown whether a dose of 1mg once daily (od) has comparable efficacy to 0.5mg bid.

Aims & Methods

In this prospective study conducted at two tertiary referral centers for EoE, we enrolled consecutive patients with EoE undergoing clinical, endoscopic, and histologic re-assessment while on maintenance treatment for EoE with BOT 0.5mg bid or BOT 1mg od. All included patients had achieved histological remission (i.e., <15 eosinophils/high-power field, eos/HPF) following induction of remission with BOT 1mg bid. At the end of the induction of remission period (T0), all patients were assessed using the dysphagia symptom questionnaire (DSQ), the EoE endoscopic reference score (EREFS), and peak eosinophil counts (PEC). At re-assessment while on maintenance treatment (T1), all patients underwent 1) assessment of dysphagia and adaptive behaviors with the DSQ and the Pisa EoE Adaptation Questionnaire v1.0 (PiEAQ). Clinical remission was defined as DSQ not increasing >30% compared to T0. 2) upper endoscopy (EGDS) with assessment of EREFS score and at least six esophageal biopsies, and 3) histological assessment using the EoE Histology Scoring System (EoEHSS). In addition, a comprehensive global assessment of clinical, endoscopic, and histologic findings was performed using the validated index of severity for EoE (I-SEE score). Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. Significance threshold was p<0.05.

Results

Fifty-six patients were included (46 males and 10 females). Following histological remission with BOT 1mg bid, 28 (50%) initiated maintenance treatment with BOT 1mg od and 28 (50%) with BOT 0.5 bid. At the end of induction of remission (T0), the two groups had achieved similar outcomes, with comparable median DSQ [0 (0-28) vs 0 (0-28)], EREFS [1 (0-2) vs 1 (0-1)], and PEC [1 (0-7) vs 1.5 (0-4)] (all p>0.3) (Table 1). At the end of the maintenance treatment (T1), the two groups had been taking maintenance treatment for a comparable duration [20 weeks (12 – 36) vs 20 weeks (12 – 32; p=0.7). Persistent histological and clinical remission at T1 was present in 86% of BOT 1mg od versus 93% of BOT 0.5 bid (p=0.7). In addition, EREFS scores were comparable between groups at T1 [1 (0-2) vs 1 (0-2), p=0.8]. Similarly, the EoEHSS stage and grade was comparable between groups, as was the PiEAQ score [1.5 (0.75-2) vs 0.5 (0-2); p=0.06], and the I-SEE score [ 3 (2-4) vs 3 (2-4); p=0.5] (Table 2).

Conclusion

Persistent clinical endoscopic, and histological remission was maintained in most patients treated either with BOT 1mg od or BOT 0.5mg bid for a median of 20 weeks, indicating that the total daily dose of BOT 1mg may be more important that the frequency of administration, at least in the short term.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Alfasigma, Dr Falk Pharma, Sanofi, Malesci, JB Pharmaceuticals

Introduction

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for Irritable Bowel Syndrome (IBS), demonstrating long-term improvements in symptoms and quality of life (QOL). However, its implementation is hindered by the complexity of treatment protocols, high time and financial costs, and limited accessibility in Japan.

Aims & Methods

This study aimed to develop a smartphone-based CBT application and evaluate its effectiveness in alleviating IBS symptoms.
Adults aged 18 or older who met the Rome IV criteria for IBS and scored ≥110 on the Japanese version of the IBS Symptom Severity Index (IBSSI-J) were enrolled. Twenty-six participants were randomly assigned to either the intervention group (n = 14) or the waiting-list control group (n = 12). Outcome measures included the IBSSI-J, Japanese versions of the IBS-QOL (IBS-QOL-J), Pain Catastrophizing Scale (PCS-J), and Visceral Sensitivity Index (VSI-J). A two-way ANOVA was conducted with group (intervention vs. control) and time (pre, mid, post, follow-up 1) as independent variables.
The intervention group used the app for 5–10 minutes daily over two months. The app included three components: psychoeducation, cognitive restructuring, and exposure. Psychoeducation consisted of educational materials and follow-up quizzes. Cognitive restructuring used gamified multiple-choice content (135 items), replacing conventional thought records. Exposure involved users creating individual anxiety hierarchies and recording their thoughts before and after exercises. The app visualized anxiety changes and progress via graphs.

Table 1.
Intervention module of the application

Results

Eleven participants in the intervention group and eight in the control group completed the program. Significant group × time interactions were observed for all outcome measures. For the IBSSI-J, the interaction was significant (F(3, 51) = 4.41, p < .001), with the intervention group showing greater improvement at mid-point (F(1, 17) = 5.54, p = .03, η² = .25). For the IBS-QOL-J, a significant interaction was found (F(3, 51) = 8.00, p < .001), with improvement evident at follow-up 1 (F(1, 17) = 6.65, p = .02, η² = .28). For the PCS-J, the interaction was significant (F(3, 51) = 3.83, p = .02), with improvements at post (F(1, 17) = 9.26, p = .01, η² = .35) and follow-up 1 (F(1, 17) = 5.83, p = .03, η² = .26). For the VSI-J, the interaction also reached significance (F(3, 51) = 3.32, p = .05).

Conclusion

The CBT-based app was effective in reducing IBS symptom severity. Its effects persisted after the intervention and extended to improvements in QOL, visceral anxiety, and pain catastrophizing—psychological factors associated with the maintenance and exacerbation of IBS. It is assumed that the cognitive restructuring component of the app facilitated cognitive diversification among participants. By empirically challenging the plausibility of these diversified cognitions through behavioral experiments in the form of exposure tasks, participants were able to further develop more adaptive thoughts. This process is considered to have contributed to the improvement of symptoms and enhancement of QOL. This digital approach may offer a viable solution to current barriers in CBT access.

Introduction

Primary sclerosing cholangitis (PSC) is known to present characteristic cholangiographic findings; however, detailed observations using peroral cholangioscopy (POCS) have rarely been reported. We previously reported that POCS findings in PSC can be classified into three types: active (inflammatory), chronic (scarring), and tumorous (tumor-like). These findings may aid in the differential diagnosis of PSC and may be useful in predicting prognosis.

Aims & Methods

We aimed to analyze POCS findings in PSC in detail based on this classification and to clarify their characteristics by evaluating the frequency of each finding, their temporal changes, and comparisons with other biliary diseases.
We retrospectively reviewed 22 patients with PSC who underwent POCS between February 2018 and February 2023. For comparison, we included 19 cases of hepatolithiasis, 25 cases of cholangiocarcinoma, and 3 cases of IgG4-related sclerosing cholangitis (IgG4-SC). Twelve POCS findings were categorized into three types: active (mucosal erythema, ulcers, fibrous white exudates, irregular surface), chronic (longitudinal scarring, annular scarring, pseudodiverticula, stenosis), and tumorous (dilated vessels, tortuous vessels, friability, mass formation). In addition, we included “punched-out lesion (POL)” as an original finding. Each finding was graded on a 5-point scale (0–4) based on the extent or number of lesions, and scores were calculated for each type. We conducted three analyses: (1) correlation between cholangiographic and POCS findings in PSC, (2) temporal changes in POCS findings in PSC, and (3) comparison of POCS findings between PSC and other biliary diseases.

Results

In the first analysis, annular scarring (100%), stenosis (89%), POL (89%), and longitudinal scarring (86%) were frequently observed in PSC. Annular scarring was identified in all cases with a shaggy appearance on cholangiography, and stenosis were present in all ducts with band-like stricture. In ducts showing diverticulum-like outpouchings, longitudinal and annular scarring, pseudodiverticula, and POL were consistently seen, whereas other findings were absent. In the second analysis, active and tumorous scores varied over time even within the same case, whereas chronic scores remained stable or showed a progressive increase. A negative correlation was observed between active and chronic scores (p-value <0.001, r =-0.702). In the third analysis, chronic findings and POL were significantly more common in PSC compared to other diseases (p-value <0.001). Pseudodiverticula were seen exclusively in PSC, while dilated and tortuous vessels and friability were significantly more frequent in cholangiocarcinoma and IgG4-SC (p-value <0.001).

Conclusion

These findings suggest that the characteristic cholangiographic findings of PSC are mainly formed by chronic scarring. Diverticulum-like outpouchings reflect only fibrotic changes. Furthermore, the coexistence of inflammation and fibrosis, along with the time-dependent progression of fibrosis, is a unique feature of PSC, although active inflammation may obscure chronic findings. Finally, longitudinal scarring and POL were particularly prominent in PSC, and pseudodiverticula were highly specific to this disease, suggesting their usefulness in differential diagnosis. In conclusion, chronic findings on POCS are characteristic of PSC and may serve as a helpful tool in its diagnosis and differentiation from other biliary diseases.

References

T Fujisawa, M Ushio, S Takahashi, et al., Role of Peroral Cholangioscopy in the Diagnosis of Primary Sclerosing Cholangitis. Diagnostics (Basel), 2020. 10(5).
T Itoi, T Kamisawa, Y Igarashi, et al., The role of peroral video cholangioscopy in patients with IgG4-related sclerosing cholangitis. J Gastroenterol, 2013. 48(4): p. 504-14.
T H Karlsen, T Folseraas, D Thorburn, et al., Primary sclerosing cholangitis - a comprehensive review. J Hepatol, 2017. 67(6): p. 1298-1323.
T Nakazawa, K Notohara, S Tazuma, et al., The 2016 diagnostic criteria for primary sclerosing cholangitis. J Gastroenterol, 2017. 52(7): p. 838-844.
T Nakazawa, H Ohara, H Sano, et al., Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc, 2004. 60(6): p. 937-44.
H Isayama, S Tazuma, N Kokudo, et al., Clinical guidelines for primary sclerosing cholangitis 2017. J Gastroenterol, 2018. 53(9): p. 1006-1034.
W L Campbell, M S Peterson, M P Federle, et al., Using CT and cholangiography to diagnose biliary tract carcinoma complicating primary sclerosing cholangitis. AJR Am J Roentgenol, 2001. 177(5): p. 1095-100.

Introduction

The diagnosis of Coeliac Disease (CD) in adults still continues to rely heavily on duodenal histology, in spite of several studies demonstrating a positive predictive value (PPV) of 100% for Marsh 3 histology when anti-tissue transglutaminase (TTG) exceeds 10x upper limit of normal. The majority of these studies come from tertiary centres and the slow uptake of the non biopsy approach may be as a result of limited data on the histological outcome of positive serology originating in the primary care setting.

Aims & Methods

To determine the PPV of primary care-based TTG testing with concurrent anti-endomysial antibody (EMA) positivity for histological diagnosis of CD.
The immunology lab in our institution performs reflex EMA testing on all newly positive and newly borderline positive TTG samples from the West of Ireland (TTG≥5U/ml Celikey by Phadia). Over a 6 year period (2018-2023), 1,361 index TTG positive samples also proved positive when tested for EMA. Following electronic medical record review, we excluded all samples from patients who were <16 years old, had a previous diagnosis of CD made elsewhere, lacked biopsy data, or had biopsies that predated the serological test. Patients who had their coeliac serology testing requested by any hospital-based physician were also excluded to ensure that only patients identified by primary care-based screening were included in the outcome analysis. In this manner, 335 adult patients who had serology screening performed by their primary care physician were eligible for further analysis. These eligible patients were then stratified by TTG levels ( ≤20, 21-69, and ≥70 U/ml). PPV was calculated for each stratum. Logistic regression assessed the relationship between TTG values and biopsy results. Additional analyses examined influence of interval between serology and biopsy.

Results

Chi-square analysis confirmed significant association between TTG levels and biopsy results (p<0.00001). For each 10 U/ml increase in TTG, odds of positive biopsy increased by 18% (OR 1.18, 95% CI: 1.10-1.26). For TTG 21-69 U/ml, PPV declined with longer serology-to-biopsy intervals: 100% for ≤47 days versus 45.2% for >203 days. High TTG values maintained excellent PPV regardless of interval. Long-term follow-up of initially biopsy-negative patients revealed subsequent CD diagnosis in 19/40 (47.5%) in the low titre group, 11/30 (36.7%) in the intermediate group, and 7/11 (63.6%) in the high titre group.

Conclusion

TTG titre significantly predicts biopsy-confirmed CD, with TTG ≥70 U/ml having 90.4% PPV. The predictive value of intermediate TTG diminishes with increasing interval between serology and biopsy. A substantial portion of initially biopsy-negative patients across all TTG strata were subsequently diagnosed with CD during follow-up. These findings support TTG in risk-stratifying CD patients, suggest prompt biopsies for intermediate TTG values, and highlight the importance of long-term monitoring even in patients with negative initial biopsies.

References

1. Husby S, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-60.
2. Penny HA, et al. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut. 2021;70(5):876-883.

Introduction

Depression and anxiety are common yet underrecognized comorbidities in patients with pancreatitis. While evidence suggests a significant psychological burden in these patients, the underlying mechanisms remain unclear, and psychological management is not routinely implemented in clinical care. This study aims to assess the prevalence of these conditions and highlight the need for their integration into pancreatitis treatment.

Aims & Methods

Our protocol was registered on PROSPERO (CRD42023481739). We conducted a comprehensive search on November 10, 2023, across three databases - MEDLINE, Embase, and CENTRAL - to identify studies reporting on the prevalence of depression and anxiety symptoms in patients with pancreatitis. We used a random-effects model to calculate the pooled proportion rate and mean differences (MD) with 95% confidence intervals (CI), as well as a pooled single-mean analysis of the psychological questionnaire data.

Results

In total, 43 studies were included in our meta-analysis. Among patients with acute pancreatitis (AP), anxiety was reported in approximately 23% of cases (CI: 7-54), whereas in chronic pancreatitis (CP), the prevalence was higher at 31% (CI: 23-39). Depressive symptoms were identified in approximately 29% of AP patients (CI: 14-51) and 39% of CP patients (CI: 30-48). The pooled single-mean analysis of questionnaire data further underscored the severity of these psychological symptoms, with scores exceeding established clinical cut-off points. For depressive symptoms, mean scores were as follows: CESD-10 (14.30 [CI: 6.69-21.92]), HADS (8.23 [CI: 4.53-11.94]), and SES (49.29 [CI: 44.01-54.57]). Similarly, anxiety symptom severity was reflected in the following measures: HADS (8.67 [CI: 4.53-11.94]) and SAS (47.75 [CI: 35.05-60.45])

Conclusion

There is a significant prevalence of both anxiety and depression in patients with pancreatitis. There is a need to integrate psychological interventions into the treatment of pancreatitis to potentially improve clinical outcomes.

Introduction

Pancreatic cancer is particularly notable for its aggressive progression and dismal prognosis, which underscores the urgent need for the development of novel therapeutic strategies that can effectively combat this formidable disease. Recent investigations have brought to light the potential of salvianolic acid B (SalB), a polyphenolic compound that is extracted from the roots of the Salvia miltiorrhiza plant, as a promising candidate for targeted cancer treatment. However, the precise mechanisms through which SalB influences metabolic changes in pancreatic cancer cells and promotes ferroptosis—a specific type of programmed cell death characterized by iron-dependent lipid peroxidation—remain to be fully elucidated. Therefore, this study aims to thoroughly investigate the impact of SalB on the metabolic reprogramming of pancreatic cancer cells, while also clarifying the specific mechanisms by which it induces ferroptosis.

Aims & Methods

We established an in situ mouse model of pancreatic cancer to evaluate SalB's anti-tumor effects at 10, 30, and 100 μM, assessing critical parameters like glutathione (GSH) levels, glutathione peroxidase 4 (GPX4) activity, malondialdehyde (MDA) production, reactive oxygen species (ROS) levels, ferrous iron (Fe2+) concentrations, mitochondrial morphology, ATP levels, enzyme activity, mitochondrial ROS, and mitochondrial membrane potential (MMP) in Panc-1, BxPC-3, and SW1990 cell lines. We also used Fer-1 to inhibit ferroptosis and reevaluated SalB's effects, exploring its relationship with ferroptosis in pancreatic cancer cells.

Results

SalB significantly reduced tumor volume in mice afflicted with in situ pancreatic cancer, all while notably not impacting the body weight of these animals, suggesting a targeted therapeutic effect without the common side effects associated with weight loss. In various cell lines, including Panc-1, BxPC-3, and SW1990, treatment with SalB resulted in a marked decline in levels of GSH and GPX4, which are crucial for cellular antioxidant defense. This decline was coupled with a significant increase in MDA and ROS, indicating that SalB effectively induces oxidative stress within the cells, a condition that can lead to cell death. Furthermore, SalB treatment led to elevated intracellular levels of Fe2+, alterations in mitochondrial morphology, a decrease in MMP, and reduced ATP levels, alongside inhibited activity of mitochondrial respiratory chain enzymes and increased production of mitochondrial ROS. These changes collectively confirm SalB's potent ability to inhibit mitochondrial function while simultaneously improving the overall metabolic condition in pancreatic cancer cells. Following pretreatment with the ferroptosis inhibitor Fer-1, the reductions in GSH, GPX4, and MMP levels, as well as the increases in MDA, ROS, and Fe2+ levels induced by SalB, were effectively reversed, demonstrating the dynamic interplay between these cellular components. Additionally, Fer-1 restored ATP levels and the diminished activity of mitochondrial respiratory chain enzymes caused by SalB treatment, while also attenuating the production of mitochondrial ROS. These findings underscore the critical role of ferroptosis in mediating the effects of SalB on mitochondrial function and highlight its significant impact on the overall metabolic state of pancreatic cancer cells, suggesting a promising avenue for therapeutic intervention.

Conclusion

SalB effectively suppresses pancreatic cancer progression by inducing ferroptosis and mitochondrial metabolic reprogramming.

References

[1] Riva G, Pea A, Pilati C, et al. Histo-molecular oncogenesis of pancreatic cancer: From precancerous lesions to invasive ductal adenocarcinoma. World J Gastrointest Oncol. 2018;10(10):317-327.
[2] Li M, Tao J, Qian R, et al. Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis. Front Genet. 14:1086368.
[3] Qin T, Rasul A, Sarfraz A, et al. Salvianolic acid A & B: potential cytotoxic polyphenols in battle against cancer via targeting multiple signaling pathways. Int J Biol Sci. 2019;15(10):2256-2264.