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2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Qi Li ◽  
Zijian Feng ◽  
Ruyi Miao ◽  
Xun Liu ◽  
Chenxi Liu ◽  
...  

Abstract Background The overall survival of patients  with pancreatic cancer is extremely low. Despite multiple large-scale studies, identification of predictors of patient survival remains challenging. This study aimed to investigate the prognostic factors for pancreatic cancer. Methods The clinical data of 625 patients with pancreatic cancer treated at Shengjing Hospital of China Medical University from January 2013 to December 2017 were collected. Results Of 625 patients, 569 were followed from 1 to 75 months. The median overall survival was 9.3 months. The overall 1-, 3-, and 5-year survival rates were 37.8%, 15.1%, and 10.5%, respectively. Cox proportional hazards model indicated that baseline carbohydrate antigen 199 level, neutrophil-lymphocyte ratio, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of patients with pancreatic cancer. Baseline carbohydrate antigen 199 level, degree of weight loss, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of pancreatic head cancer subgroup. Baseline carbohydrate antigen 199 level, carcinoembryonic antigen level, total bilirubin level, neutrophil-lymphocyte ratio, peripancreatic invasion, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of the pancreatic body/tail cancer subgroup. Conclusions Higher carbohydrate antigen 199 levels, neutrophil-lymphocyte ratio, lymph node metastasis and distant organ metastasis predict a poor prognosis in patients with pancreatic cancer. Early detection, early radical surgery and adjuvant chemotherapy are needed to improve prognosis for this deadly disease.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenjie Zhang ◽  
Juan Xing ◽  
Tian Liu ◽  
Jie Zhang ◽  
Zhujiang Dai ◽  
...  

AbstractPancreatic cancer is a highly malignant tumor and, is extremely difficult to diagnose and treat. Metastasis is one of the critical steps in the development of cancer and uses cell to cell communication to mediate changes in the microenvironment. Small extracellular vesicles (sEVs)-carry proteins, nucleic acids and other bioactive substances, and are important medium for communication between cells. There are two primary steps in sVEs-mediated metastasis: communication between pancreatic cancer cells and their surrounding microenvironment; and the communication between primary tumor cells and distant organ cells in distant organs that promotes angiogenesis, reshaping extracellular matrix, forming immunosuppressive environment and other ways to form appropriate pre-metastasis niche. Here, we explore the mechanism of localization and metastasis of pancreatic cancer and use sEVs as early biomarkers for the detection and treatment of pancreatic cancer. Graphical Abstract


2021 ◽  
Vol 219 (1) ◽  
Author(s):  
Julia Bolik ◽  
Freia Krause ◽  
Marija Stevanovic ◽  
Monja Gandraß ◽  
Ilka Thomsen ◽  
...  

Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis. We show that TNFR1-dependent tumor cell–induced endothelial cell death, tumor cell extravasation, and subsequent metastatic seeding is dependent on the activity of endothelial ADAM17. Moreover, we reveal that ADAM17-mediated TNFR1 ectodomain shedding and subsequent processing by the γ-secretase complex is required for the induction of TNF-induced necroptosis. Consequently, genetic ablation of ADAM17 in endothelial cells as well as short-term pharmacological inhibition of ADAM17 prevents long-term metastases formation in the lung. Thus, our data identified ADAM17 as a novel essential regulator of necroptosis and as a new promising target for antimetastatic and advanced-stage cancer therapies.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lei Chen ◽  
Zhiwen Wang ◽  
Songlin Song ◽  
Tao Sun ◽  
Yanqiao Ren ◽  
...  

Background. Recently, radiotherapy has been used in the treatment of hepatocellular carcinoma (HCC). However, there is no study analyzing the efficacy of radiotherapy in cases of advanced HCC. The objective of this investigation was to determine the efficacy of radiotherapy in patients with HCC invading distant organs. Methods. The data of 2342 patients diagnosed between 2010 and 2015 with HCC invading distant organs were extracted from the SEER database. Propensity score matching (PSM) was used to reduce selection bias. Results. Before PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group (mOS = 5 months, 95% CI: 4.5–5.5; mCSS = 5 months, 95% CI: 4.4–5.6) were longer than those in the nonradiotherapy group (mOS = 3 months, 95% CI: 2.8–3.2; mCSS = 3 months, 95% CI: 2.8–3.2; both P < 0.001 ). After PSM, mOS in the radiotherapy group (5 months, 95% CI: 4.5–5.5) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6–3.4; P < 0.001 ), and the mCSS in the radiotherapy group (5 months, 95% CI: 4.4–5.6) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6–3.4; P < 0.001 ). Before PSM, the multivariate analysis showed that all-cause and cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group. The adjusted Cox regression analysis for subgroups showed that, in the nonradiotherapy group, patients with bone metastases and multiorgan metastases had a worse survival than those in the radiotherapy group. Conclusion. HCC patients with metastases to distant organs obtain survival benefit from radiotherapy, particularly patients with bone metastases and multiorgan metastases.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4937
Author(s):  
Johannes Linxweiler ◽  
Anja Kolbinger ◽  
Dirk Himbert ◽  
Philip Zeuschner ◽  
Matthias Saar ◽  
...  

Extracellular vesicles (EVs) secreted by cancer cells have been shown to take a pivotal part in the process of local and systemic tumor progression by promoting the formation of a supportive local tumor microenvironment and preparing premetastatic niches in distant organ systems. In this study, we analyzed the organ-specific uptake of EVs secreted by urological cancer cells using an innovative in-vivo approach. EVs from benign and malignant prostate, kidney, and bladder cells were isolated using ultracentrifugation, fluorescence-labeled and injected intravenously in immunodeficient mice. After 12 or 24 h, the animals were sacrificed, their organs were harvested and analyzed for the presence of EVs by high-resolution fluorescence microscopy. Across all entities, EVs were taken up fast (12 h > 24 h), and EVs from malignant cells were taken up more efficiently than EVs from benign cells. Though not entirely organ-specific, EVs were incorporated in different amounts, depending on the entity (prostate: lung > liver > brain; kidney: brain > lung > liver; bladder: lung > liver > brain). EV uptake in other organs than lung, liver, brain, and spleen was not observed. Our results suggest a role of EVs in the formation of premetastatic niches and an organotropism in EV uptake, which have to be examined in more detail in further studies.


2021 ◽  
Vol 15 (3) ◽  
pp. 192-197
Author(s):  
Fernanda de Lima Correa ◽  
Luciana Wolfran ◽  
Aline de Marco Viott ◽  
Juliana das Chagas Goulart ◽  
Flávio Shigueru Jojima ◽  
...  

The transmissible venereal tumour (TVT) is one of the most frequent neoplasias in dogs. This tumour has specific characteristics, and it is exclusively of canines. Its transmission occurs through viable neoplastic cell transplantation when in contact with mucosa or unhealthy skin and rarely metastasise. This paper aims to report a rare presentation of pulmonary metastasis of widespread transmissible venereal tumours in a Blue Heeler dog. The patient was cachectic, dyspnoeic, and dehydrated and had multiple skin and pharynx nodulations. The cytology of all cutaneous nodulations showed round vacuolated cells with large eccentric nuclei and loose chromatin, which is compatible with TVT’s microscopic characteristics. Owing to the clinical evolution and reserved prognosis, the patient was euthanized. Necroscopy revealed a mass in the right pulmonary caudal lobe. The mass showed the same histopathologic characteristic of the others: not encapsulated infiltrative neoplastic proliferation of round vacuolated cells. The atypical manifestation of cutaneous metastasis and mainly pulmonary metastasis, in this case, denote the importance of TVT inclusion as a differential in cutaneous neoplasia, even if they show distant organ metastasis. Therefore, it emphasised the importance of cytology and histology in the diagnosis of nodular affections.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dominik Funken ◽  
Yi Yu ◽  
Xiaoyan Feng ◽  
Tawan Imvised ◽  
Faikah Gueler ◽  
...  

AbstractT-cells have been demonstrated to modulate ischemia–reperfusion injury (IRI) in the kidney, lung, liver, and intestine. Whereas most T-cell subpopulations contribute primarily to the antigen-specific effector and memory phases of immunity, γδ-T-cells combine adaptive features with rapid, innate-like responses that can place them in the initiation phase of immune reactions. Therefore, we aimed to clarify the role of γδ-T-cells in intestinal IRI. Adult wild-type (WT) and γδ-T-cell-deficient mice were subjected to acute intestinal IRI. Gene expression of pro-inflammatory cytokines and influx of leukocyte subpopulations in the gut were assessed by qPCR and flow cytometry. Serum transaminases were measured as an indicator of distant organ IRI. Intestinal IRI led to increased influx of neutrophils, pro-inflammatory cytokine expression and LDH/ALT/AST elevation. Selective deficiency of γδ-T-cells significantly decreased pro-inflammatory cytokine levels and neutrophil infiltration in the gut following IRI compared to controls. Furthermore, γδ-T-cell deficiency resulted in decreased LDH and transaminases levels in sera, indicating amelioration of distant organ injury. Increasing evidence demonstrates a key role of T-cell subpopulations in IRI. We demonstrate that γδ-T-cell deficiency ameliorated pro-inflammatory cytokine production, neutrophil recruitment and distant organ injury. Thus, γδ-T-cells may be considered as mediators contributing to the inflammatory response in the acute phase of intestinal IRI.


2021 ◽  
Author(s):  
RAJNIKANT DIXIT

Abstract Periodic ingestion of a protein-rich blood meal by adult female mosquitoes causes a drastic metabolic change in their innate physiological status, which is referred to as ‘metabolic switch. Although the down-regulation of olfactory factors is key to restrain host-attraction, how the gut ‘metabolic switch’ modulates brain functions, and resilience physiological homeostasis remains unexplored. Here we demonstrate that the protein-rich diet induces the expression of brain transcripts related to mitochondrial function and energy metabolism, possibly to cause a shift of the brain’s engagement to manage organismal homeostasis. A dynamic expression pattern of neuro-signalling and neuro-modulatory genes in both gut and brain, establishes an active brain-distant organ communication. Disruption of this comunication through decapitation, does not affect the modulation of the neuro-modulator receptor genes in the gut. In parallel, an unusual and paramount shift in the level of the Neurotransmitters (NTs), from the brain to the gut after blood feeding, further supports the idea of the gut’s ability to serve as a ‘second brain’. Finally, a comparative metagenomics evaluation of gut microbiome population dynamics, highlighted that blood-feeding not only suppresses Enterobacteriaceae family member by 50%, but favors rapid proliferation of Pseudomonadales to 46% of the total community. Notable obesrvation of a rapid proliferation of Pseudomonas bacterial sp. in the gut correlates a possible cause for the suppression of appetite after blood-feeding. Additionally, an altered NTs dynamics of naïve and aseptic mosquitoes provide the initial evidence that gut-endosymbionts are key modulators for the synthesis of major neuroactive molecules. Conclusion: Our data establish a new conceptual understanding of microbiome-gut-brain-axis communication in mosquitoes.Data deposition: Mosquito Brain RNAseq data are accessible under Accession IDs: SRR9853884 (Ac-Br-SF); SRR9853885 (Ac-Br-BF-30Min), SRR9853883 (Ac-Br-BF-30hrs) at NCBI repository. Mosquito Gut metagenomics data are accessible under accession IDs: SRR12579422 (Ac-MG-SF); SRR12622557 (Ac-MG-BF) at NCBI repository.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weilin Zhang ◽  
Wei Zhao ◽  
Qin Li ◽  
Duoyi Zhao ◽  
Junxing Qu ◽  
...  

AbstractMelatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesium–polycaprolactone (Mg–PCL) scaffold and investigated its effect and molecular mechanism on CIC in OS. Mg–PCL scaffold was prepared by 3D-printing and its characteristic was determined. The effect and molecular mechanism of Mg–PCL scaffold as well as melatonin-loaded Mg–PCL on OS growth and progression were investigated in vivo and in vitro. We found that melatonin receptor 1 (MT1) and CIC expressions were increased in OS tissues and cells. Melatonin treatment inhibit the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus playing an anti-invasion and anti-metastasis role in OS. The Mg–PCL–MT could significantly inhibit distant organ metastasis of OS in the in vivo model. Our results showed that melatonin-loaded Mg–PCL scaffolds inhibited the proliferation, invasion and metastasis of OS cells through the CIC pathway. The Mg–PCL–MT could be a potential therapeutics for OS.


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