Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.
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ABSTRACT:
SUBMITTER: Xu M
PROVIDER: S-EPMC8160269 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.
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Project description:The liver is the most common site of metastases for colorectal cancer. Complete resection in some patients with resectable liver metastases (LM) can lead to long-term survival and cure. Adjuvant systemic chemotherapy after complete resection of LM improves recurrence-free survival; however, the overall survival benefit is not clear. In selected patients, preoperative systemic treatment for metastatic colorectal cancer can convert unresectable to resectable cancer. This review will focus on patient selection, and integration of perioperative and postoperative systemic treatment to surgery in resectable and initially unresectable LM. Additionally, new drugs and biomarkers will be discussed.
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Project description:BackgroundCurrently, there is a lack of an effective strategy for the prevention of peritoneal metastasis (PM) from locally advanced gastric cancer (AGC). This randomized-controlled study aimed to evaluate the outcome of D2 radical resection with hyperthermic intraperitoneal chemotherapy (HIPEC) plus systemic chemotherapy versus systemic chemotherapy alone in locally AGC patients.MethodsAll enrolled patients were randomly assigned to receive HIPEC plus systemic chemotherapy (HIPEC group) or systemic chemotherapy alone (non-HIPEC group) after radical gastrectomy. HIPEC was performed intraperitoneally with cisplatin (40 mg/m2) within 72 h after surgery, while systemic chemotherapy based on the SOX regimen (S-1 combined with oxaliplatin) was administered 4-6 weeks after radical surgery. Patterns of recurrence, adverse events, 3-year disease-free survival (DFS), and overall survival (OS) were analyzed.ResultsA total of 134 patients were enrolled in the present study. The 3-year DFS rate was 73.8% in the HIPEC group, which was significantly higher than that in the non-HIPEC group (61.2%, P = 0.031). The 3-year OS rate was 73.9% in the HIPEC group and 77.6% in the non-HIPEC group, with no significant difference (P = 0.737). PM was the most common distant metastasis in both groups. The occurrence rate of PM in the HIPEC group was statistically lower than that in the non-HIPEC group (20.9% vs. 40.3%, P = 0.015). Grade 3 or 4 adverse events occurred in 19 (14.2%) patients, and there was no significant difference between the two groups.ConclusionRadical surgery followed by HIPEC combined with systemic chemotherapy is a safe and feasible strategy for locally AGC patients and could effectively improve DFS and reduce the occurrence of PM. However, more prospective randomized studies with a large sample size are warranted.Trial registrationThis study was registered with www.medresman.org.cn as ChiCTR2200055966 on 10/12/2016.
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Project description:Primary tumors and distant site metastases form a bidirectionally communicating system. Yet, the molecular mechanisms of this crosstalk are poorly understood. Here, we identified the proteolytically cleaved fragments of angiopoietin-like 4 (ANGPTL4) as contextually active protumorigenic and antitumorigenic contributors in this communication ecosystem. Preclinical studies in multiple tumor models revealed that the C-terminal fragment (cANGPTL4) promoted tumor growth and metastasis. In contrast, the N-terminal fragment of ANGPTL4 (nANGPTL4) inhibited metastasis and enhanced overall survival in a postsurgical metastasis model by inhibiting WNT signaling and reducing vascularity at the metastatic site. Tracing ANGPTL4 and its fragments in tumor patients detected full-length ANGPTL4 primarily in tumor tissues, whereas nANGPTL4 predominated in systemic circulation and correlated inversely with disease progression. The study highlights the spatial context of the proteolytic cleavage-dependent pro- and antitumorigenic functions of ANGPTL4 and identifies and validates nANGPTL4 as a novel biomarker of tumor progression and antimetastatic therapeutic agent.
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Project description:INTRODUCTION:Surgery in SCLC is limited to very early stages, but several reports suggest a potential broader role. Little is known of the influence of microenvironment on the biology of SCLC. METHODS:We assessed the clinical prognostic factors in a large series of resected SCLC patients. The prognostic value of programmed cell death ligand 1 (PD-L1) expression in tumor cells and tumor infiltrating lymphocytes (TILs) and the percentage of CD3-, CD20-, CD45- and CD68-positive cells, were also investigated. RESULTS:Two hundred five SCLC cases were resected between 2005 and 2015 and the median follow-up was 29 months (range: 2 to 135 months). Median survival of all patients was 69 months, and 5-year survival rates were 63.8%, 65.5%, 34.9%, and 0% for pathologic stages I, II, III, and IV, respectively. By multivariate analysis complete resection, cigarette index, lymph node metastatic rate, percentage of CD3-positive cells, PD-L1 expression in tumor cells, and TILs were independent prognostic factors. High PD-L1 expression was present in 3.2% and 33.5% of all tumor samples in tumor cells and TILs, respectively. High PD-L1 expression in tumor cells or TILs correlated with shorter survival, whereas high expression of CD3, CD20, and CD45 correlated with better survival. CONCLUSIONS:Resected stage II SCLC patients have similar survival as stage I, suggesting that surgery could be extended to patients with hilar lymph node involvement. Survival was better in tumors with a higher percentage of T cells and B cells, whereas PD-L1 expression in tumor cells and TILs correlated with worse survival, which suggests a potential role of immunotherapy in resected SCLC.
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Project description:PurposeChildren with brain tumors experience cognitive late effects, often related to cranial radiation. We sought to determine differential effects of surgery and chemotherapy on brain structure and neuropsychological outcomes in children who did not receive cranial radiation therapy (CRT).MethodsTwenty-eight children with a history of posterior fossa tumor (17 treated with surgery, 11 treated with surgery and chemotherapy) underwent neuroimaging and neuropsychological assessment a mean of 4.5 years (surgery group) to 9 years (surgery + chemotherapy group) posttreatment, along with 18 healthy sibling controls. Psychometric measures assessed IQ, language, executive functions, processing speed, memory, and social-emotional functioning. Group differences and correlations between diffusion tensor imaging findings and psychometric scores were examined.ResultsThe z-score mapping demonstrated fractional anisotropy (FA) values were ≥2 standard deviations lower in white matter tracts, prefrontal cortex gray matter, hippocampus, thalamus, basal ganglia, and pons between patient groups, indicating microstructural damage associated with chemotherapy. Patients scored lower than controls on visuoconstructional reasoning and memory (P ≤ .02). Lower FA in the uncinate fasciculus (R = -0.82 to -0.91) and higher FA in the thalamus (R = 0.73-0.91) associated with higher IQ scores, and higher FA in the thalamus associated with higher scores on spatial working memory (R = 0.82).ConclusionsPosterior fossa brain tumor treatment with surgery and chemotherapy affects brain microstructure and neuropsychological functioning years into survivorship, with spatial processes the most vulnerable. Biomarkers indicating cellular changes in the thalamus, hippocampus, pons, prefrontal cortex, and white matter tracts associate with lower psychometric scores.
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Project description:ObjectiveThe change of bacterial flora structure in colorectal cancer (CRC) patients after treatment is not clear. The aim of this study was to explore the change and function of intestinal microflora in CRC before and after treatment.MethodThe 16S conserved region V3+V4 of intestinal flora obtained from CRC patients was sequenced and analyzed. Alpha and beta diversity indices were used to analyze the abundance and structure of gut flora. FAPROTAX, BugBase, and Tax4Fun software were used to analyze the species phenotypes and Kyoto Encyclopedia of Genes and Genomes Ontology (KO) function pathways.ResultsTotal abundance and structure of species in CRC patients were significantly increased compared with healthy people (control group) (P < 0.05), but there was no significant difference between CRC patients before and after treatment (P > 0.05). There was significant difference in relative abundance of bacteria at different levels (phylum, class, order, family, genus, and species) between the CRC group with after operation (CRC_O group) and chemotherapy (CRC_C group) treatment, particularly Prevotellaceae_UCG-001, Akkermansia, Fusicatenibacter, Tyzzerella_4, Megamonas, etc. in genus level. The KO function analysis showed that most of the bacteria with differences were mainly involved in the biosynthesis of lipopolysaccharide (Megamonas, Megasphaera, and Ruminococcus torques_group), protein digestion and absorption, renin-angiotensin system pathway (Akkermansia, Eubacterium_ruminantium_group, and Eubacterium_nodatum_group genus), adipocytokine signaling pathway and peroxisome pathway (Tyzzerella_4, Phascolarctobacterium, Ruminococcus_gnavus_group), and so on.ConclusionThe abundance of intestinal microflora in CRC patients was increased significantly contrasted to healthy people, and surgery and chemotherapy were hard to reduce this phenomenon. Megamonas was involved in lipopolysaccharide biosynthesis and carcinogenesis in colorectal cancer. Surgery and drug treatment did not reduced lipopolysaccharide biosynthesis but increased the number of probiotic Akkermansia population and reduced the pathogenic bacteria Tyzzerella_4, participate in adipocytokine signaling pathway, and affect metabolism.
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