CA : A Cancer Journal for Clinicians

https://www.rs.tus.ac.jp/iwakuralab/pdf/review_il17family.pdf

Functional Specialization of Interleukin-17 Family Members

The journal of pharmacology and experimental therapeutics

In the United States, the incidence rate of new or recurrent stroke is approximately 795 000 per year, and stroke prevalence for individuals over the age of 20 years is estimated at 6.5 million.1 Mortality rates in the first 30 days after stroke have decreased because of advances in emergency medicine and acute stroke care. In addition, there is strong evidence that organized postacute, inpatient stroke care delivered within the first 4 weeks by an interdisciplinary healthcare team results in an absolute reduction in the number of deaths.2,3 Despite these positive achievements, stroke continues to represent the leading cause of long-term disability in Americans: An estimated 50 million stroke survivors worldwide currently cope with significant physical, cognitive, and emotional deficits, and 25% to 74% of these survivors require some assistance or are fully dependent on caregivers for activities of daily living (ADLs).4,5

Notwithstanding the substantial progress in acute stroke care over the past 15 years, the focus of stroke medical advances and healthcare resources has been on acute and subacute recovery phases, which has resulted in substantial health disparities in later phases of stroke care. Additionally, healthcare providers (HCPs) are often unaware of not only patients’ potential for improvement during more chronic recovery phases but also common issues that stroke survivors and their caregivers experience. Furthermore, even with evidence that documents neuroplasticity potential regardless of age and time after stroke,6 the mean lifetime cost of ischemic stroke (which accounts for 87% of all strokes) in the United States is an estimated $140 000 (for inpatient, rehabilitation, and follow-up costs), with 70% of first-year stroke costs attributed to acute inpatient hospital care1; therefore, fewer financial resources appear to be dedicated to providing optimal care during the later phases of stroke recovery.

Because there remains a …

Comprehensive Overview of Nursing and Interdisciplinary Rehabilitation Care of the Stroke Patient A Scientific Statement From the American Heart Association

Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.

Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors☆

Th17 cells that produce IL-17 have been found to participate in the development of allergy-triggered asthma. However, whether they play a causative role in the pathogenesis of airway remodeling in chronic asthma remains unclear. In this study, we investigated the role of Th17 cells in airway remodeling and the possible involvement of epidermal growth factor (EGF) receptor signals downstream of Th17. We established a C57BL/6 mouse model of prolonged allergen challenge that exhibits many characteristics of airway remodeling. Prolonged allergen challenge induced a progressive increase in the number of airway-infiltrating Th17 cells, and Th17 counts positively correlated with the severity of airway remodeling. Increases in mucus production, airway smooth muscle (ASM) mass, peribronchial collagen deposition, and airway heparin-binding EGF (HB-EGF) expression have been observed in sensitized mice following prolonged allergen exposure or adoptive Th17 transfer; remarkably, these effects can be abrogated by treatment with anti-IL-17 mAb. Both the EFGR inhibitor AG1478 and an anti-HB-EGF mAb ameliorated all of these effects, except for peribronchial collagen deposition in the presence of high levels of IL-17. In vitro, Th17 cells enhanced the airway epithelial expression of HB-EGF in a coculture of the two cells. The conditioned medium obtained from this coculture system effectively promoted ASM proliferation; this response was dramatically abolished by anti-HB-EGF mAb but not Abs against other EGF receptor ligands or IL-17. These observations demonstrated that overexpression of airway HB-EGF induced by IL-17 secreted from redundant expanding Th17 cells might contribute to excessive mucus expression and ASM proliferation in chronic asthma.

/pdf/the-overexpression-of-heparin-binding-epidermal-growth-4yb0uzlehj.pdf

The overexpression of heparin-binding epidermal growth factor is responsible for Th17-induced airway remodeling in an experimental asthma model.

During infection, triggering receptor expressed on myeloid cells-2 (TREM-2) restrains dendritic cells (DCs) and macrophages (MΦs) phagocytosis, as well as reduces pro-inflammatory cytokines release through DNAX-activation protein 12 (DAP12) signaling. However, the role of TREM-2 signaling in cancer has never been elucidated. In the current study, we found that TREM-2 was up-regulated on peripheral blood monocytes in tumor-bearing host. More TREM-2+DCs were detected in the lung of 3LL tumor-bearing mice. On the other hand, the level of TREM-2 on pulmonary MΦs positively correlated with the pathological staging of lung cancer. However, surgical or chemotherapeutic reduction of tumor burden led to the obvious decline of TREM-2. In vitro, TREM-2 expression of bone marrow (BM)-derived DCs and MΦs was induced by conditional medium (CM) containing the supernatant of 3LL cells. TREM-2+DCs from CM and/or tumor-bearing mice held altered phenotypes (CD80LowCD86LowMHCIILow) and impaired functions, such as, reduced interleukin (IL)-12 secretion, increased IL-10 production, and weakened ovalbumin (OVA)-endocytic capacity; also developed potent inhibitory effect on T cell proliferation that could be partially reversed by TREM-2 blockage. Moreover, spleen tyrosine kinase (Syk) inhibitor restrained IL-10 production of TREM-2+DC. Remarkably, IL-10 neutralizing antibody and Syk inhibitor both lowered the suppressive potential of TREM-2+DCs in T cell proliferation. Also, adoptive transfer of this TREM-2+DCs accelerated the tumor growth rather than jeopardized survival in lung cancer-bearing mice. In conclusion, these results indicate that TREM-2 might act as a negative immuno-regulatory molecule through Syk pathway in an IL-10 dependent manner and partially predicts prognosis in lung cancer patients.

TREM-2 serves as a negative immune regulator through Syk pathway in an IL-10 dependent manner in lung cancer

Palbociclib, a selective CDK4/6 inhibitor, enhances the effect of selumetinib in RAS-driven non-small cell lung cancer.

Tumour-associated macrophage (TAM) is an important component in tumour microenvironment. Generally, TAM exhibits the function of M2-like macrophage, which was closely related to angiogenesis and tumour progression. Dioscin, a natural steroidal saponin, has shown its powerful anti-tumour activity recently. However, the mechanism of dioscin involved in immune regulation is still obscure. Here, we observed dioscin induced macrophage M2-to-M1 phenotype transition in vitro and inhibited IL-10 secretion. Meanwhile, the phagocytosis of macrophages was enhanced. In subcutaneous lung tumour models, dioscin inhibited the augmentation of M2 macrophage populations. Furthermore, dioscin down-regulated STAT3 and JNK signalling pathways in macrophages in vitro. In BMDMs, activating JNK and inhibiting STAT3 induce macrophages to M1 polarization while inhibiting JNK and activating STAT3 to M2 polarization. Additionally, condition mediums from dioscin-pre-treated macrophages inhibited the migration of 3LL cells and the tube-formation capacity of HUVECs. What's more, dioscin-mediated macrophage polarization inhibited the in vivo metastasis of 3LL cells. In conclusion, dioscin may act as a new anti-tumour agent by inhibiting TAMs via JNK and STAT3 pathways in lung cancer.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.15563

Yinan Yao

Papers

Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors☆

The overexpression of heparin-binding epidermal growth factor is responsible for Th17-induced airway remodeling in an experimental asthma model.

TREM-2 serves as a negative immune regulator through Syk pathway in an IL-10 dependent manner in lung cancer

Palbociclib, a selective CDK4/6 inhibitor, enhances the effect of selumetinib in RAS-driven non-small cell lung cancer.

Dioscin elicits anti-tumour immunity by inhibiting macrophage M2 polarization via JNK and STAT3 pathways in lung cancer.