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Cancer is the second leading cause of death worldwide. Although multiple new cancer treatments have emerged in recent years, drug therapy, mainly comprising chemotherapy, targeted therapy, and immunotherapy, remains the most common approach. The multidrug resistance (MDR) of cancer cells to various treatments remains a challenge. Scientists have always focused on the acquired drug resistance mechanisms of tumor cells themselves. However, recent evidence shows that the tumor microenvironment (TME) plays a critical role in regulating tumor cell progression, metastasis, immune escape, and drug resistance. In the TME, interactions between cancer cells and non-malignant cells often modify the TME and facilitate drug resistance. Therefore, elucidating this complex interaction mechanism is essential for the development of effective treatments. This review focuses on the role of the TME in promoting chemoresistance in tumor cells through the following mechanisms: (i) inhibiting the immune clearance of tumor cells and facilitating immune escape responses; (ii) stimulating the release of soluble paracrine factors to enhance tumor survival and growth; (iii) promoting survival and altering drug delivery through metabolic reprogramming; (iv) obstructing drug absorption by inducing changes in stomatal cells and blood vessels surrounding the tumor; and (v) inducing the cancer stem cell phenotype. This review also addresses a clinical treatment strategy for targeting the TME, providing insights and a basis for reversing multidrug resistance. [ABSTRACT FROM AUTHOR]

Background: Epithelial-to-mesenchymal transition (EMT) is a process linked to metastasis and drug resistance with non-coding RNAs (ncRNAs) playing pivotal roles. We previously showed that miR-100 and miR-125b, embedded within the third intron of the ncRNA host gene MIR100HG, confer resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in colorectal cancer (CRC). However, whether the MIR100HG transcript itself has a role in cetuximab resistance or EMT is unknown. Methods: The correlation between MIR100HG and EMT was analyzed by curating public CRC data repositories. The biological roles of MIR100HG in EMT, metastasis and cetuximab resistance in CRC were determined both in vitro and in vivo. The expression patterns of MIR100HG, hnRNPA2B1 and TCF7L2 in CRC specimens from patients who progressed on cetuximab and patients with metastatic disease were analyzed by RNAscope and immunohistochemical staining. Results: The expression of MIR100HG was strongly correlated with EMT markers and acted as a positive regulator of EMT. MIR100HG sustained cetuximab resistance and facilitated invasion and metastasis in CRC cells both in vitro and in vivo. hnRNPA2B1 was identified as a binding partner of MIR100HG. Mechanistically, MIR100HG maintained mRNA stability of TCF7L2, a major transcriptional coactivator of the Wnt/β-catenin signaling, by interacting with hnRNPA2B1. hnRNPA2B1 recognized the N6-methyladenosine (m6A) site of TCF7L2 mRNA in the presence of MIR100HG. TCF7L2, in turn, activated MIR100HG transcription, forming a feed forward regulatory loop. The MIR100HG/hnRNPA2B1/TCF7L2 axis was augmented in specimens from CRC patients who either developed local or distant metastasis or had disease progression that was associated with cetuximab resistance. Conclusions: MIR100HG and hnRNPA2B1 interact to control the transcriptional activity of Wnt signaling in CRC via regulation of TCF7L2 mRNA stability. Our findings identified MIR100HG as a potent EMT inducer in CRC that may contribute to cetuximab resistance and metastasis by activation of a MIR100HG/hnRNPA2B1/TCF7L2 feedback loop. [ABSTRACT FROM AUTHOR]

Highlights • We produced chimeric influenza VLPs of membrane-anchored forms of LTB and Flic. • The chimeric VLPs generated greater immune responses when compared with H5N1 VLPs. • IM immunization with VLPs protected mice of challenge with heterologous viruses. • Oral immunization with chimeric VLPs conferred protection of influenza challenge. Abstract We previously demonstrated that intramuscular immunization with virus-like particles (VLPs) composed of the haemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) protected mice from lethal challenge with viruses from other H5 HPAI clades. The inclusion of additional proteins that can serve as immunological adjuvants in VLPs may enhance adaptive immune responses following vaccination, and oral vaccines may represent the safest choice. Here, we report the generation of H5N1 VLPs composed of the viral HA, NA, and M1 proteins and membrane-anchored forms of the Escherichia coli heat-labile enterotoxin B subunit protein (LTB) or the Toll-like receptor 5 ligand flagellin (Flic). Mice intramuscularly or orally immunized with VLPs containing LTB or Flic generated greater humoural and cellular immune responses than those administered H5N1 VLPs without LTB or Flic. Intramuscular immunization with VLPs protected mice from lethal challenge with homologous or heterologous H5N1 viruses irrespective of whether the VLPs additionally included LTB or Flic. In contrast, oral immunization of mice with LTB- or Flic-VLPs conferred substantial protection against lethal challenge with both homologous and heterologous H5N1 influenza viruses, whereas mice immunized orally with VLPs lacking LTB and Flic universally succumbed to infection. Mice immunized orally with LTB- or Flic-VLPs showed 10-fold higher virus-specific IgG titres than mice immunized with H5N1-VLPs lacking LTB or Flic. Collectively, these results indicate that the inclusion of immunostimulatory proteins, such as LTB and Flic, in VLP-based vaccines may represent a promising new approach for the control of current H5N1 HPAI outbreaks by eliciting higher humoural and cellular immune responses and conferring improved cross-clade protection. [ABSTRACT FROM AUTHOR]

The H7N9 influenza virus epidemic has been associated with a high mortality rate in China. Therefore, to prevent the H7N9 virus from causing further damage, developing a safe and effective vaccine is necessary. In this study, a vaccine candidate consisting of virus-like particles (VLPs) based on H7N9 A/Shanghai/2/2013 and containing hemagglutinin (HA), neuraminidase (NA), and matrix protein (M1) was successfully produced using a baculovirus (BV) expression system. Immunization experiments showed that strong humoral and cellular immune responses could be induced by the developed VLPs when administered via either the intramuscular (IM) or intranasal (IN) immunization routes. Notably, VLPs administered via both immunization routes provided 100% protection against lethal infection caused by the H7N9 virus. The IN immunization with 40 μg of H7N9 VLPs induced strong lung IgA and lung tissue resident memory (TRM) cell-mediated local immune responses. These results provide evidence for the development of an effective preventive vaccine against the H7N9 virus based on VLPs administered through both the IM and IN immunization routes. [ABSTRACT FROM AUTHOR]

Background and Objective: Colorectal cancer (CRC) is the third most common cancer worldwide, and the incidence and mortality rates continue to increase annually. Many factors, including genetic, immune, and environmental factors, influence the occurrence and development of CRC. Along with the economic development, changes in lifestyle, especially dietary factors, have been shown to greatly affect the progression of CRC. Increasing evidence showed that dietary patterns influence the risk of CRC and affect CRC treatment. The present review describes the role of diet in the prevention and treatment of CRC with the hope that doctors attach importance to dietary patterns in educating patients with CRC or at risk of CRC and that diet may be regarded as an auxiliary treatment strategy to improve patients' outcomes., Methods: English language articles published from 2000 to December 2021 in PubMed and Embase were identified by searching titles for keywords including "diet", "colorectal cancer", "dietary pattern", and "dietary factor"; 101 articles were selected for review., Key Content and Findings: The present review describes the role of different dietary patterns and factors in the prevention and treatment of CRC. We found that dietary intervention is closely related to the occurrence, development, and prognosis of CRC. Adherence to the Mediterranean diet (MD), the Dietary Approaches to Stop Hypertension (DASH) diet, fasting, vegetarian diets and the ketogenic diet (KD) were found to reduce the risk of CRC, prolong patient survival, and delay disease progression. Moderate intake of dietary fiber (DF), omega-3 fatty acids, micronutrients (e.g., calcium, iron, and selenium), and vitamins have been shown to be beneficial in the prevention and treatment of CRC. Conversely, diets high in fat or sugar and those rich in red meat or processed meat promote CRC., Conclusions: People at high risk of CRC and those with CRC are recommended to eat a plant-based diet rich in fruits, vegetables, and whole grains with appropriate DF intake and to avoid high levels of processed meat, red meat, and highly refined grains., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-32/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

This study was performed to observe the effect of the combination of nimotuzumab with radiation or gemcitabine-based chemoradiation on antipancreatic cancer cell therapy. Pancreatic cancer cells (PANC-1) were treated with nimotuzumab alone or combined with radiation (2, 4, or 8 Gy), which was either with or without gemcitabine chemotherapy. Cell proliferation, cell cycle distribution, and apoptosis were observed. The inhibition rate, the percentage of G2/M phase arrest, and the apoptosis rate of the combined nimotuzumab with radiation group was significantly higher than the group without nimotuzumab (P < .001). The inhibition rate, the percentage of G2/M phase, and the apoptosis rate of the nimotuzumab therapy combined with gemcitabine-based chemoradiation group were obviously higher than that in gemcitabine-based chemoradiation group (P < .001). In conclusion, nimotuzumab could enhance the anticancer effect of radiation and gemcitabine-based chemoradiation in PANC-1 cancer cells because of the enhancement of cell cycle arrest and apoptosis., (© The Author(s) 2015.)

Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs) composed of the hemagglutinin (HA), neuraminidase (NA) and matrix protein (M1) of A/Changchun/01/2009 (H1N1) with or without either membrane-anchored cholera toxin B (CTB) or ricin toxin B (RTB) as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival). Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses.