scholarly journals Surgery for Colorectal Cancer: A Trigger for Liver Metastases Development? New Insights into the Underlying Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 177
Author(s):  
Simran Grewal ◽  
Steven J. Oosterling ◽  
Marjolein van Egmond
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Survival Rates ◽  
Metastatic Progression ◽  
Term Survival ◽  
Metastasis Development ◽  
Potential Trigger ◽  
Underlying Mechanisms

Surgery is a crucial intervention and provides the best chance of cure for patients with colorectal cancer. Experimental and clinical evidence, however, suggests that paradoxically surgery itself may precipitate or accelerate tumor recurrence and/or liver metastasis development. This review addresses the various aspects of surgery-induced metastasis formation and sheds light on the role of inflammation as potential trigger for metastasis development. Understanding these mechanisms may provide potential new perioperative interventions to improve treatment outcomes, and as such could transform the perioperative timeframe from a facilitator of metastatic progression to a window of opportunity to reduce the risk of liver metastasis development. Ultimately, this can potentially improve long-term survival rates and quality of life in patients with colorectal cancer.

scholarly journals Macrophages in Organ Transplantation

2020 ◽  
Vol 11 ◽  
Author(s):  
Farideh Ordikhani ◽  
Venu Pothula ◽  
Rodrigo Sanchez-Tarjuelo ◽  
Stefan Jordan ◽  
Jordi Ochando
Keyword(s):  
Immune Response ◽  
Organ Transplantation ◽  
Survival Rates ◽  
Adaptive Immune Response ◽  
Phagocytic Cells ◽  
Term Survival ◽  
Vast Number ◽  
Monocytes And Macrophages

Current immunosuppressive therapy has led to excellent short-term survival rates in organ transplantation. However, long-term graft survival rates are suboptimal, and a vast number of allografts are gradually lost in the clinic. An increasing number of animal and clinical studies have demonstrated that monocytes and macrophages play a pivotal role in graft rejection, as these mononuclear phagocytic cells recognize alloantigens and trigger an inflammatory cascade that activate the adaptive immune response. Moreover, recent studies suggest that monocytes acquire a feature of memory recall response that is associated with a potent immune response. This form of memory is called “trained immunity,” and it is retained by mechanisms of epigenetic and metabolic changes in innate immune cells after exposure to particular ligands, which have a direct impact in allograft rejection. In this review article, we highlight the role of monocytes and macrophages in organ transplantation and summarize therapeutic approaches to promote tolerance through manipulation of monocytes and macrophages. These strategies may open new therapeutic opportunities to increase long-term transplant survival rates in the clinic.

scholarly journals Long-Term Survival of Campylobacter jejuni at Low Temperatures Is Dependent on Polynucleotide Phosphorylase Activity

2009 ◽  
Vol 75 (23) ◽  
pp. 7310-7318 ◽  
Author(s):  
Nabila Haddad ◽  
Christopher M. Burns ◽  
Jean Michel Bolla ◽  
Hervé Prévost ◽  
Michel Fédérighi ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Low Temperatures ◽  
Survival Rates ◽  
Polynucleotide Phosphorylase ◽  
Wild Type ◽  
Term Survival ◽  
Poultry Products ◽  
Bacterial Gastroenteritis

ABSTRACT Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. Infection generally occurs after ingestion of contaminated poultry products, usually conserved at low temperatures. The mechanisms promoting survival of C. jejuni in the cold remain poorly understood despite several investigations. The present study provides insight into the survival mechanism by establishing the involvement of polynucleotide phosphorylase (PNPase), a 3′-5′ exoribonuclease with multiple biological functions in cold survival. The role of PNPase was demonstrated genetically using strains with altered pnp genes (which encode PNPase) created in C. jejuni F38011 and C. jejuni 81-76 backgrounds. Survival assays carried out at low temperatures (4 and 10°C) revealed a difference of 3 log CFU/ml between the wild-type and the pnp deletion (Δpnp) strains. This did not result from a general requirement for PNPase because survival rates of the strains were similar at higher growth temperatures (37 or 42°C). trans-Complementation with plasmid pNH04 carrying the pnp gene under the control of its natural promoter restored the cold survival phenotype to the pnp deletion strains (at 4 and 10°C) but not to the same level as the wild type. In this study we demonstrate the role of PNPase in low-temperature survival of C. jejuni and therefore attribute a novel biological function to PNPase directly related to human health.

scholarly journals The role of the immunoescape in colorectal cancer liver metastasis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259940
Author(s):  
Chie Takasu ◽  
Shoko Yamashita ◽  
Yuji Morine ◽  
Kozo Yoshikawa ◽  
Takuya Tokunaga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Survival Rates ◽  
Hazard Ratio ◽  
Prognostic Indicators ◽  
Programmed Death ◽  
Immune Molecule ◽  
Programmed Death 1 ◽  
Positive Groups

The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.

scholarly journals Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

2020 ◽  
Vol 21 (15) ◽  
pp. 5207 ◽  
Author(s):  
Francesca Cersosimo ◽  
Silvia Lonardi ◽  
Giulia Bernardini ◽  
Brian Telfer ◽  
Giulio Eugenio Mandelli ◽  
...  
Keyword(s):  
Patient Survival ◽  
Survival Rates ◽  
Tumor Stroma ◽  
Therapeutic Management ◽  
Metastatic Progression ◽  
Tumor Associated Macrophages ◽  
Poor Patient ◽  
Metastasis Development ◽  
Patient Prognosis

Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating macrophages that are known to orchestrate many aspects of OS stromal signaling and disease progression. In particular, increased infiltration of M2-like tumor-associated macrophages (TAMs) has been associated with OS metastasis and poor patient prognosis despite currently used aggressive therapies regimens. This review aims to provide a summary update of current macrophage-centered knowledge and to discuss the possible roles that macrophages play in the process of OS metastasis development focusing on the potential influence of stromal cross-talk signaling between TAMs, cancer-stem cells and additional OSs tumoral microenvironment factors.

Survival investigation in patients with colorectal liver metastasis: A single-institution analysis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 617-617
Author(s):  
Jianmin Xu ◽  
Dexiang Zhu ◽  
Li Ren ◽  
Ye Wei
Keyword(s):  
Liver Resection ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Median Survival ◽  
Colorectal Liver Metastasis ◽  
Survival Rates ◽  
Term Survival ◽  
Long Term Survival ◽  
Primary Colorectal Tumor

617 Background: To investigate survival in patients with colorectal liver metastasis (CRLM) and identify risk factors associated with survival. Methods: Clinical, pathologic, treatment and complete follow-up data were retrospectively collected from 1613 consecutive patients with CRLM in Zhongshan Hospital between 2000 and 2010. The prognostic value of different factors was studied through univariate and multivariate analyses. Results: The median survival was 22.0 mo and 5-yr survival rate was 16%. Survival of synchronous liver metastases (SLM) (21.2 mo and 16%) was lower than that of metachronous liver metastases (MLM) (30.1 mo and 23%, p<0.01). Survival after resection of liver metastases was 49.8 mo and 37%, higher than that after chemotherapy (22.2 mo and 0%), that after intervention(19.0 mo and 11%), that after chemotherapy combined with intervention(22.8 mo and 10%)and that after local regional treatment (28.5 mo and 0%). Expansion of the indications for liver resection (38.0 vs 48.0 mo, 32% vs 40%), simultaneous or staged resection of primary colorectal tumor and liver metastases (47.0 vs 44.0 mo, 33% vs 35%) and preoperative neoadjuvant therapy (44.0 vs 48.0 mo, 38% vs 36%) had no significant effect on survival. 64 initially irresectable patients could undergo surgery after convertible therapy, with the median survival 36.9 mo and 5-yr survival 30%, better than that of unresectable patients (18.2 mo and 8%). Five factors were found to be significant and independent predictors of poor survival by multivariate analysis: SLM, poorly differentiated primary, number of liver metastases >= 4, largest liver metastases >= 5 cm, and no surgical treatment of liver metastases. Giving one point to each above factor, the population was divided into six groups with 5-yr survival rates: 0 (64%), 1 (44%), 2 (29%), 3 (4%), 4 (4%) and 5 (1%) (p<0.01). Conclusions: Survival of SLM was lower than that of MLM. Resection of liver metastases provides good long-term survival benifit for patients with resectable and initially irresectable liver metastases. Expansion of the indications for liver resection is acceptable. Long-term survival outcome can be predicted from a risk factor scoring system.

scholarly journals The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

2020 ◽  
Vol 21 (10) ◽  
pp. 3494
Author(s):  
Aldona Kasprzak ◽  
Agnieszka Adamek
Keyword(s):  
Colorectal Cancer ◽  
Nervous System ◽  
Liver Metastasis ◽  
Current Knowledge ◽  
Distant Metastases ◽  
Colorectal Cancer Liver Metastases ◽  
Functional Changes ◽  
Metastasis Development ◽  
Research Challenge

Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain–tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.

scholarly journals Role of Clp Proteins in Expression of Virulence Properties of Streptococcus mutans

2009 ◽  
Vol 191 (7) ◽  
pp. 2060-2068 ◽  
Author(s):  
Jessica K. Kajfasz ◽  
Alaina R. Martinez ◽  
Isamar Rivera-Ramos ◽  
Jacqueline Abranches ◽  
Hyun Koo ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Mutational Analysis ◽  
Slow Growth ◽  
Global Regulator ◽  
Term Survival ◽  
Virulence Traits ◽  
Underlying Mechanisms

ABSTRACT Mutational analysis revealed that members of the Clp system, specifically the ClpL chaperone and the ClpXP proteolytic complex, modulate the expression of important virulence attributes of Streptococcus mutans. Compared to its parent, the ΔclpL strain displayed an enhanced capacity to form biofilms in the presence of sucrose, had reduced viability, and was more sensitive to acid killing. The ΔclpP and ΔclpX strains displayed several phenotypes in common: slow growth, tendency to aggregate in culture, reduced autolysis, and reduced ability to grow under stress, including acidic pH. Unexpectedly, the ΔclpP and ΔclpX mutants were more resistant to acid killing and demonstrated enhanced viability in long-term survival assays. Biofilm formation by the ΔclpP and ΔclpX strains was impaired when grown in glucose but enhanced in sucrose. In an animal study, the average number of S. mutans colonies recovered from the teeth of rats infected with the ΔclpP or ΔclpX strain was slightly lower than that of the parent strain. In Bacillus subtilis, the accumulation of the Spx global regulator, a substrate of ClpXP, has accounted for the ΔclpXP phenotypes. Searching the S. mutans genome, we identified two putative spx genes, designated spxA and spxB. The inactivation of either of these genes bypassed phenotypes of the clpP and clpX mutants. Western blotting demonstrated that Spx accumulates in the ΔclpP and ΔclpX strains. Our results reveal that the proteolysis of ClpL and ClpXP plays a role in the expression of key virulence traits of S. mutans and indicates that the underlying mechanisms by which ClpXP affect virulence traits are associated with the accumulation of two Spx orthologues.

scholarly journals SURGICAL OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH SYNCHRONOUS COLORECTAL LIVER METASTASES

2014 ◽  
Vol 51 (1) ◽  
pp. 4-9 ◽  
Author(s):  
Rafael FONTANA ◽  
Paulo HERMAN ◽  
Vincenzo PUGLIESE ◽  
Marcos Vinicius PERINI ◽  
Fabricio Ferreira COELHO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Colorectal Liver Metastases ◽  
Disease Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Disease Free

Context Colorectal cancer is the second most prevalent cancer worldwide, and the liver is the most common site of metastases. Surgical resection of colorectal liver metastases provides the sole possibility of cure and the best odds of long-term survival. Objectives To describe surgical outcomes and identify features associated with disease prognosis in patients submitted to synchronous colorectal cancer liver metastasis resection. Methods Retrospective study of 59 patients who underwent surgery for synchronous colorectal cancer liver metastasis. Actuarial survival and disease-free survival were assessed, depending on the prognostic variable of interest. Results Postoperative mortality and morbidity rates were 3.38% and 30.50% respectively. Five-year disease-free survival was estimated at 23.96%, and 5-year overall survival, at 38.45%. Carcinoembryonic antigen levels ≥50 ng/mL and presence of three or more liver metastasis were limiting factors for disease-free survival, but did not affect late survival. No patient with liver metastases and extrahepatic disease had disease-free interval longer than 20 months, but this had no significance or impact on long-term survival. None of the prognostic factors assessed had an impact on late survival, although no patients with more than three liver metastases survived beyond 40 months. Conclusions Although Carcinoembryonic antigen levels and number of metastases are prognostic factors that limit disease-free survival, they had no impact on 5-year survival and, therefore, should not determine exclusion from surgical treatment. Resection is the best treatment option for synchronous colorectal liver metastases, and even for patients with multiple metastases, large tumors and extrahepatic disease, it can provide long-term survival rates over 38%.

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