Circulating tumor DNA-based stratification strategy for chemotherapy plus PD-1 inhibitor in advanced non-small-cell lung cancer.

Stratification strategies for chemotherapy plus PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) are critically demanded. We performed high-throughput panel-based deep next-generation sequencing and low-pass whole genome sequencing on prospectively collected circulating tumor DNA (ctDNA) specimens from 460 patients in the phase 3 CHOICE-01 study at different time points. We identified predictive markers for chemotherapy plus PD-1 inhibitor, including ctDNA status and genomic features such as blood-based tumor mutational burden, intratumor heterogeneity, and chromosomal instability. Furthermore, we established an integrated ctDNA-based stratification strategy, blood-based genomic immune subtypes (bGIS) scheme, to distinguish patients who benefit from the addition of PD-1 inhibitor to first-line chemotherapy. Moreover, we demonstrated potential applications for the dynamic monitoring of ctDNA. Overall, we proposed a potential therapeutic algorithm based on the ctDNA-based stratification strategy, shedding light on the individualized management of immune-chemotherapies for patients with advanced NSCLC.

A Review of the Efficacy and Mechanisms of Blood Flow Restriction Training in Enhancing Somatic Function and Preventing Falls in Older Adults.

Falls have become an important public health problem that seriously affects the quality of survival of older adults and are a major cause of fractures, death, and reduced quality of life. With the advent of an aging society, the social, economic, and medical burdens of falls in older adults are increasing. Currently, there is a lack of effective means to prevent falls in older adults, and traditional health education and clinical interventions are not effective. It is urgent to find a safe and effective training method that can improve balance function and is suitable for the elderly. Low-intensity blood flow restriction training (BFRT) is an emerging training modality that, by restricting blood flow to the limbs and combining it with low-intensity exercise, can effectively improve muscle mass, aerobic capacity, and bone density, and has been shown to enhance somatic function in older adults. However, the effectiveness and specific mechanisms of BFRT in preventing falls in older adults are unclear. Based on recent research progress, this paper explores the possibility of BFRT in preventing falls in older adults by analyzing its positive effects on muscle mass, balance function, and cognitive function, the risk factors of falling in the elderly are summarized, as well as its potential role in reducing fall risk factors. It aims to provide new thinking for academia and clinical practice and to provide a scientific basis for reducing the risk of falls in the elderly.

Demethylzeylasteral ameliorates podocyte damage in murine lupus by inhibiting inflammation and enhancing autophagy.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan and tissue involvement. Lupus nephritis (LN), an inflammatory condition of the kidneys associated with SLE, represents a significant cause of morbidity and mortality in SLE patients. Current immunosuppressive therapies for LN have limited efficacy and can lead to significant side effects. Demethylzeylasteral (DML) has shown promise in the treatment of LN, but its precise mechanism of action remains unclear. PURPOSE: To assess the therapeutic effects and potential molecular mechanisms of DML in LN METHODS: The study evaluated the renal protective effects of DML in MRL/lpr mice through assessments of immune complex levels, renal function, and pathological changes. Network pharmacology and transcriptomics approaches were used to elucidate the underlying mechanisms. Molecular docking, biacore assay, monoclonal antibody blocking experiments, and in vitro studies were conducted to verify the mechanisms of action. RESULTS: DML treatment reduced levels of anti-Sm and anti-dsDNA IgG antibodies, as well as serum creatinine and blood urea nitrogen levels. DML also mitigated glomerular damage and fibrosis. Mechanistically, DML alleviated podocyte damage by suppressing inflammation and enhancing autophagy through inhibition of the IL-17A/JAK2-STAT3 pathways. Additionally, DML exhibited high binding affinity with IL17A, JAK2, and STAT3. CONCLUSION: These findings provide strong evidence for the beneficial effects of DML in LN, suggesting its potential as a novel therapeutic strategy for improving renal function in autoimmune kidney diseases.

Brain-tumor-seeking and serpin-inhibiting outer membrane vesicles restore plasmin-mediated attacks against brain metastases.

Many chemotherapeutic and molecular targeted drugs have been used to treat brain metastases, e.g., anti-angiogenic vandetanib. However, the blood-brain barrier and brain-specific resistance mechanisms make these systemic therapeutic approaches inefficacious. Brain metastatic cancer cells could mimic neurons to upregulate multiple serpins and secrete them into the extracellular environment to reduce local plasmin production to promote L1CAM-mediated vessel co-option and resist anti-angiogenesis therapy. Here, we developed brain-tumor-seeking and serpin-inhibiting outer membrane vesicles (DE@OMVs) to traverse across the blood-brain barrier, bypass neurons, and specially enter metastatic cancer cells via targeting GRP94 and vimentin. Through specific delivery of dexamethasone and embelin, reduced serpin secretion, restored plasmin production, significant L1CAM inactivation and tumor cell apoptosis were specially found in intracranial metastatic regions, leading to delayed tumor growth and prolonged survival in mice with brain metastases. By combining the brain-tumor-seeking properties with the regulation of the serpin/plasminogen activator/plasmin/L1CAM axis, this study provides a potent and highly-selective systemic therapeutic option for brain metastases.

Divergent sensory pathways of sneezing and coughing.

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.

Effects of actinomycetes on the growth, antioxidant and genes expression in Fritillaria taipaiensis P. Y. li.

F. taipaiensis P. Y. Li represents a significant asset within traditional Chinese medicinal flora, though it confronts the challenge of germplasm deterioration during its cultivation phase. This study aimed to discern the implications of single strains or combinations of diverse growth-promoting actinomycetes on the growth metrics, antioxidant competence and pertinent gene expression in the leaves of F. taipaiensis. The result revealed that the malondialdehyde content within the plant's leaves notably diminished in the treatment groups compared to the CK group, with the S6 group showcasing the most pronounced malondialdehyde reduction, amounting to approximately one-third of the CK's value. Leaf area, length and width peaked in the S5 cohort, registering values 4.55, 2.46 and 1.85 times surpassing the CK group. Concurrently, plant height and stem thickness were maximal in the S6 group, being 2.29 and 1.75 times that of the CK group, whereas leaf thickness reached its zenith in the S7 group, marking a 2.17-fold elevation compared to the CK. Photosynthetic pigments, soluble sugars and soluble proteins in the leaves, exhibited augmentation across the inoculated groups to varying magnitudes. Specifically, the S5 group was superior in photosynthetic metrics and pigments, while the S6 group manifested the highest soluble sugar concentration, which was 1.35 times that of the CK. The S3 group demonstrated the pinnacle of soluble protein content, an impressive 5.86-fold increment relative to the CK group. The enzymatic activities of superoxide dismutase, peroxidase and catalase, along with their affiliated gene expressions, were observably augmented in the inoculated groups, with the S5 group standing out. To encapsulate, the actinomycete inoculation holds potential in fostering the growth and maturation of F. taipaiensis, amplifying its environmental resilience. The revelations from this study extend valuable insights for the judicious choice of microbial fertilizers in the cultivated propagation of Fritillaria taipaiensis P. Y. Li.

A qualitative study on the disease coping experiences of pancreatic cancer patients and their spouses.

Cancer affects patients as well as their spouses. Patients and their spouses use different strategies to cope with cancer and the associated burden. This study aimed to gain a deeper and more differentiated understanding of support systems for patients and their spouses. This was an exploratory qualitative study conducted in China. The study was based on 20 semistructured face-to-face interviews. Ten pancreatic cancer patients and their spouses were interviewed. The interviews took place at a tertiary hospital from June 2023 to December 2023. The data were analysed using thematic analysis according to Braun and Clarke's methodology. This study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Twenty participants of different ages (patients: range = 49-75 years; spouses: range = 47-73 years) participated. Patients with different cancer stages (e.g., potentially resectable, borderline resectable, locally advanced) and cancer types (initial diagnosis or relapse) participated in the study. Five themes emerged from the data, namely, denial and silence, fear and worry, struggle, coping strategies and cherishing the present. Active dyadic coping is conducive to promoting disease adaptation, and spouses seem to need more psychological support to improve their own well-being. Health care providers should pay attention to pancreatic cancer patients and their spouses in terms of five themes: denial and silence, fear and worry, struggle, coping strategies and cherishing the present. Future studies should use a combination of qualitative and quantitative methods to explore dyadic coping in greater depth.

Regulatory effect of rapamycin on recruitment and function of myeloid-derived suppressor cells in heart failure.

BACKGROUND: Immune response and inflammation play important roles in the physiological and pathophysiological processes of heart failure (HF). In our previous study, myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells with anti-inflammatory and immunosuppressive functions, were shown to exert cardioprotective effects in HF. The pharmacological targeting of MDSCs using rapamycin may emerge as a promising strategy for the prevention and treatment of HF. However, the specific mechanisms underlying rapamycin-induced MDSC accumulation remain unclear. Our study aimed to clarify the effects of rapamycin on the recruitment and function of MDSCs in HF, exploring new therapeutic options for the prevention and treatment of HF. METHODS: We used transverse aortic constriction surgery and isoproterenol injection to establish HF models. Flow cytometry, reverse transcription polymerase chain reaction, transcriptomics and western blot were used to explore the regulation of rapamycin on recruitment and function of MDSCs in HF. Furthermore, rapamycin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were combined to induce exogenous MDSCs from bone marrow cells. RESULTS: Rapamycin promotes the recruitment of MDSCs by inhibiting their maturation and differentiation via suppression of the Wnt signaling in HF mice and enhanced the immunosuppressive function of MDSCs via the NF-κB signaling. Furthermore, exogenous MDSCs induced by rapamycin and GM-CSF can significantly alleviate transverse aortic constriction-induced cardiac dysfunction. CONCLUSIONS: The pharmacological targeting of MDSCs using rapamycin is a promising strategy for the prevention and treatment of HF.

Comprehending the inhibition mechanism of indole-based bis-acylhydrazone compounds on α-glucosidase: Spectral and theoretical approaches.

Indole-based bis-acylhydrazone compounds can inhibit the activity of α-glucosidase and control the concentration of blood glucose. In this paper, the characteristics of three indole-based bis-acylhydrazone compounds with different inhibitory activities of α-glucosidase as well as the interaction with α-glucosidase were studied by experiments and computational simulation techniques. Enzyme kinetic and spectral experiments showed that the indole-based bis-acylhydrazone compounds were able to inhibit enzyme activity through mixed inhibition dominated by competitive inhibition, and during the binding reaction, indole-based bis-acylhydrazone compounds can quench the intrinsic fluorescence of α-glucosidase through static quenching and an aggregation of the indole-based bis-acylhydrazone with α-glucosidase produces a stable complex with a molar ratio of 1:1, and the combination of indole-based bis-acylhydrazone compounds could lead to slight change in the conformation of α-glucosidase. The theoretical simulation demonstrated that the stability of the complex systems was positively correlated with the inhibitory activity of indole-based bis-acylhydrazone compounds, and the indole-based bis-acylhydrazone compounds occupied the active site in the multi-ligand system, resulting in a significant decrease in the binding ability of starch to active amino acids. These results suggested that indole-based bis-acylhydrazone compound was expected to be a new type of α-glucosidase inhibitor.

Application of fluorescent carbon quantum dots functional modified carboxymethyl cellulose film in toluene gas specific detection.

With the increasing consumption of organic solvents in chemical and pharmaceutical industries, the environment pollution of volatile organic compounds (VOCs) has become an urgent problem. Therefore, the rapid-visual detection method is of great significance in the analysis of VOCs. Based on the fluorescence quenching/enhancement mechanism of carbon quantum dots (CQDs), with the help of carboxymethyl cellulose membrane with porous and large specific surface area structure, a series of green CQDs@carboxymethyl cellulose composite film (CQDs@CMC composite film) was prepared in this study. In the typical-targeted pollutants (toluene) detection application, a fluorescence spectroscopy method was established which could achieve the high sensitivity and strong specificity detection. The mainly conclusions were as follows: The fluorescence spectrometric detection method for toluene: A kind of hydrophobic Lmi/Bet CQDs@CMC composite film was prepared and characterized with imidazole/betaine CQDs and porous carboxymethyl cellulose composite film as raw materials. The toluene detection performance was studied, and the recognition mechanism was explored. The results showed that toluene enhanced the fluorescence of Lmi/Bet CQDs@CMC composite film. The fluorescence intensity of composite films was proportional to toluene concentration when the toluene concentration ranged from 200 to 2200 mg/L. The detection limit of toluene was 1.169 mg/L, which provides a theoretical basis for the detection of toluene by fluorescence spectrometry.

In Vitro and In Vivo Analyses Reveal Tumor-Derived Exosome miR-558 Promotes Angiogenesis in Tongue Squamous Cell Carcinoma by Targeting Heparinase.

This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.

Wutou decoction alleviates arthritis inflammation in CIA mice by regulating Treg cell stability and Treg/Th17 balance via the JAK2/STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Wutou Decoction (WTD) is a classic traditional Chinese medicine formula, which has shown clinical efficacy in treating rheumatoid arthritis (RA). The Treg stability and Th17/Treg imbalance is an important immunological mechanism in RA progression. Whether WTD regulates CD4+ T cell subsets has not been thoroughly investigated yet. AIM OF THE STUDY: This study aimed to explore the potential role and mechanisms of WTD in regulating the diminished stability of Treg cells and the imbalance of CD4+ T cell subsets via in vivo and in vitro experiments. MATERIALS AND METHODS: Firstly, the therapeutic effects of WTD on the collagen-induced arthritis (CIA) mouse and its potential regulatory function on CD4+ T cell subsets were evaluated in vivo. Animal specimens were collected after 31 days of treatment with WTD. The anti-arthritic and anti-inflammatory effects of WTD were assessed through arthritis scoring, body weight, spleen index, serum IL-6 levels, and micro-PET/CT imaging. Gene enrichment analysis was performed to evaluate the activation T cell-related signaling pathway. Flow cytometry was used to determine the proportions of CD4+ T cell subsets in vitro and in vitro. Additionally, ELISA was used to assess the secretion of IL-10 and TGF-ß by Treg cells under inflammatory conditions. The suppressive function of Treg cells on cell proliferation under inflammatory conditions was examined using CFSE labeling. Immunofluorescence staining was performed to detect the phosphorylation levels of STAT3 in CD4+ T cells from mouse spleen tissues. Western blotting was used to evaluate the phosphorylation levels of JAK2/STAT3 in Treg cells. RESULTS: WTD significantly alleviated joint inflammation in CIA mice. WTD reduced serum IL-6 levels in CIA mice, improved their body weight and spleen index. WTD treatment inhibited the activation of CD4+ T cell subgroup-related signaling in the joint tissues of CIA mice. In vitro and in vitro experiments showed that WTD increased the proportion of Treg cells and decreased the proportion of Th17 cells in CIA mice spleen. Furthermore, WTD promoted the secretion of IL-10 and TGF-ß by Treg cells and enhanced the inhibitory capacity of Treg cells on cell proliferation under inflammatory conditions. Immunofluorescence detected decreased STAT3 phosphorylation levels in CD4+ T cells from CIA mice spleen, while western blotting revealed a decrease in JAK2/STAT3 phosphorylation levels in Treg cells in vitro. CONCLUSIONS: Inhibiting JAK2/STAT3 phosphorylation is a potential mechanism through which WTD improves Treg cell stability, balances CD4+ T cell subsets, and attenuates RA joint inflammation.

Suppressing Wnt signaling of the blood‒tumor barrier to intensify drug delivery and inhibit lipogenesis of brain metastases.

Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood‒tumor barrier (BTB). BTB activates its Wnt signaling to maintain barrier properties, e.g., Mfsd2a-mediated BTB low transcytosis. Here, we reported VCAM-1-targeting nano-wogonin (W@V-NPs) as an adjuvant of nano-orlistat (O@V-NPs) to intensify drug delivery and inhibit lipogenesis of brain metastases. W@V-NPs were proven to be able to inactivate BTB Wnt signaling, downregulate BTB Mfsd2a, accelerate BTB vesicular transport, and enhance tumor accumulation of O@V-NPs. With the ability to specifically kill cancer cells in a lipid-deprived environment with IC50 at 48 ng/mL, W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice. The combination did not induce brain edema, cognitive impairment, and systemic toxicity in healthy mice. Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.

Case report: A rare DLST mutation in patient with metastatic pheochromocytoma: clinical implications and management challenges.

Background: Pheochromocytoma is one of the most hereditary human tumors with at least 20 susceptible genes undergoing germline and somatic mutations, and other mutations less than 1% -2%. In recent years, other rare mutations have gradually been discovered to be possibly related to the pathogenesis and metastasis of pheochromocytoma. Most patients with pheochromocytoma experience common symptoms like headaches, palpitations, and sweating, while some may have less common symptoms. The diversity of symptoms, genetic mutations, and limited treatment options make management challenging. Case presentation: A 53-year-old woman was hospitalized after experiencing episodic epigastric pain for one month. A mass was found in her right adrenal gland and she underwent robot-assisted laparoscopic surgery, revealing a pheochromocytoma. At the 16-month follow-up, multiple metastatic lesions consistent with metastatic pheochromocytoma were found. A germline mutation in the dihydrolipoamide succinyltransferase (DLST) gene (c.330 + 14A>G) was detected, and despite trying chemotherapy and adjuvant therapy, the patient had a limited response with an overall survival of 27 months. Conclusions: DLST mutation is one of the rare pheochromocytoma-related mutated genes, and genetic sequencing is crucial for effective clinical management.

Investigating the proliferative inhibition of HepG2 cells by exosome-like nanovesicles derived from Centella asiatica extract through metabolomics.

Nano-particles demonstrating excellent anticancer properties have gradually found application in cancer therapy. However, their widespread use is impeded by their potential toxicity, high cost, and the complexity of the preparation process. In this study, we achieved exosome-like Centella asiatica-derived nanovesicles (ADNVs) through a straightforward juicing and high-speed centrifugation process. We employed transmission electron microscopy and nanoparticle flow cytometry to characterize the morphology, diameter, and stability of the ADNVs. We evaluated the in vitro anticancer effects of ADNVs using Cell Counting Kit-8 and apoptosis assays. Through sequencing and bicinchoninic acid protein analysis, we discovered the abundant presence of proteins and microRNAs in ADNVs. These microRNAs can target various diseases such as cancer and infection. Furthermore, we demonstrated the effective internalization of ADNVs by HepG2 cells, resulting in an increase in reactive oxygen species levels, mitochondrial damage, cell cycle arrest at the G1 phase, and apoptosis. Finally, we analyzed changes in cellular metabolites post-treatment using cell metabolomics techniques. Our findings indicated that ADNVs primarily influence metabolic pathways such as amino acid metabolism and lipid biosynthesis, which are closely associated with HepG2 treatment. Our results demonstrate the potential utility of ADNVs as anticancer agents.

Regulatory roles of dopamine D2 receptor in milk protein production and apoptosis in mammary epithelial cells.

Dopamine D2 receptors (D2Rs) play crucial roles in regulating diverse physiological functions of the central nervous system and peripheral organs. D2Rs are also expressed in mammary glands. However, which cell types express D2Rs and whether they are involved in milk production remains unclear. The present findings revealed that D2Rs are expressed in the apical regions of the lateral membranes of mammary epithelial cells (MECs) in lactating mice. We also investigated the effects of the D2R agonist bromocriptine and/or antagonist domperidone on intracellular cAMP levels, milk protein production, and apoptosis in a lactation culture model of MECs that produce major milk components like lactating MECs in vivo. We found that bromocriptine decreased intracellular cAMP levels, whereas domperidone dose-dependently neutralized this effect. Bromocriptine also inhibited casein and lactoferrin production and suppressed activities of STAT5 and glucocorticoid receptors (GRs). Domperidone neutralized the inhibition of casein production as well as STAT5 and GR inactivation induced by bromocriptine. Furthermore, D2R activation by bromocriptine induced apoptosis and inactivated ERK, a signaling molecule responsible for promoting cell proliferation and survival. Domperidone attenuated ERK inactivation and apoptosis induced by bromocriptine. These findings suggest that D2Rs play regulatory roles in milk protein production and apoptosis in MECs.

Huaier enhances the tumor-killing effect and reverses gemcitabine-induced stemness by suppressing FoxM1.

BACKGROUND: Gemcitabine is the first-line chemotherapy drug that can easily cause chemotherapy resistance. Huaier is a traditional Chinese medicine and shows an antitumor effect in pancreatic cancer, but whether it can enhance the gemcitabine chemotherapeutic response and the potential mechanism remain unknown. PURPOSE: This study was performed to explore the effect of Huaier in promoting the tumor-killing effect of gemcitabine and elucidate the possible mechanism in pancreatic cancer. METHODS: Cell Counting Kit-8 assays and colony formation assays were used to detect proliferation after different treatments. Protein coimmunoprecipitation was applied to demonstrate protein interactions. Nuclear protein extraction and immunofluorescence were used to confirm the intracellular localization of the proteins. Western blotting was performed to detect cell proliferation-related protein expression or cancer stem cell-associated protein expression. Sphere formation assays and flow cytometry were used to assess the stemness of pancreatic cancer cells. The in vivo xenograft model was used to confirm the inhibitory effect under physiological conditions, and immunohistochemistry was used to detect protein expression. RESULTS: Huaier suppressed the proliferation and stem cell-like properties of pancreatic cancer cells. We found that Huaier suppressed the expression of forkhead box protein M1 (FoxM1). In addition, Huaier inhibited FoxM1 function by blocking its nuclear translocation. Treatment with Huaier reversed the stemness induced by gemcitabine in a FoxM1-dependent manner. Furthermore, we verified the above results by an in vivo study, which reached the same conclusion as those in vitro. CONCLUSION: Overall, this study illustrates that Huaier augments the tumor-killing effect of gemcitabine through suppressing the stemness induced by gemcitabine in a FoxM1-dependent way. These results indicate that Huaier can be applied to overcome gemcitabine resistance.

Analysis of chemoresistance characteristics and prognostic relevance of postoperative gemcitabine adjuvant chemotherapy in pancreatic cancer.

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. RESULTS: Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). CONCLUSIONS: Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.