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The tumor extracellular matrix (ECM) critically regulates cancer progression and treatment response. Expression of the basement membrane component collagen XVIII (ColXVIII) is induced in solid tumors, but its involvement in tumorigenesis has remained elusive. We show here that ColXVIII was markedly upregulated in human breast cancer (BC) and was closely associated with a poor prognosis in high-grade BCs. We discovered a role for ColXVIII as a modulator of epidermal growth factor receptor tyrosine kinase (ErbB) signaling and show that it forms a complex with ErbB1 and -2 (also known as EGFR and human epidermal growth factor receptor 2 [HER2]) and [alpha]6-integrin to promote cancer cell proliferation in a pathway involving its N-terminal portion and the MAPK/ERK1/2 and PI3K/AKT cascades. Studies using Col18a1 mouse models crossed with the mouse mammary tumor virus-polyoma virus middle T antigen (MMTV-PyMT) mammary carcinogenesis model showed that ColXVIII promoted BC growth and metastasis in a tumor cell-autonomous manner. Moreover, the number of mammary cancer stem cells was significantly reduced in the MMTV-PyMT and human cell models upon ColXVIII inhibition. Finally, ablation of ColXVIII substantially improved the efficacy of ErbB-targeting therapies in both preclinical models. In summary, ColXVIII was found to sustain the stemness properties of BC cells and tumor progression and metastasis through ErbB signaling, suggesting that targeting ColXVIII in the tumor milieu may have important therapeutic potential., Introduction Breast cancer (BC) is the most common cancer among women, with over 2 million new cases diagnosed in 2020, and accounts for 25% of all female cancers (1). Treatment [...]

This review summarizes the impact of systemic and ocular inflammatory disorders on diabetes mellitus (DM) and diabetic retinopathy (DR). Local inflammation is a key pathology in diabetic retinopathy (DR) and is also an evolving target for clinical therapy. The legacy effects of local inflammation at the intracellular level make DR a persistent self-driven vicious process. Ocular inflammation is accompanied as well as incited by systemic inflammation due to diabetes mellitus (DM) itself. Over the years, a multitude of studies have evaluated the impact of systemic inflammatory disorders (SIDs, like rheumatoid arthritis, lupus, psoriasis, etc.) and anti-inflammatory drugs prescribed for managing them on manifestations of DM. Recent studies have indicated increased insulin resistance to be a result of chronic inflammation, and the anti-inflammatory drugs to have a protective effect towards DM. Very few studies have evaluated the impact of SIDs on DR. Furthermore, the evidence from these studies is conflicting, and while local anti-inflammatory therapy has shown a lot of clinical potential for use in DR, the results of systemic anti-inflammatory therapies have been inconsistent. The impact of local ocular inflammation due to uveitis on DR is a crucial aspect that has not been evaluated well at present. Initial pre-clinical studies and small-sized clinical reports have shown a strong and positive relationship between the presence of uveitis and the severity of DR as well as its progression, while larger cross-sectional patient surveys have refuted the same. The long term impact of ocular inflammation due to uveitis on DR needs to be studied while adjusting for confounders. [ABSTRACT FROM AUTHOR]

Purpose: Human ocular tissue banking plays an important part in the advancement of translational research for identifying the molecular processes involved in disease etiology and pathogenesis. Timely obtaining a good‑quality ocular tissue from a cadaveric donor is exceedingly difficult, especially in remote areas, with a variable transportation time (within 12–24 h), raising concerns about RNA quality and its subsequent applications. Therefore, we assessed the utility of retinal tissues from cadaver donor and enucleated eyes based on the RNA quality and gene expression by real‑time polymerase chain reaction (PCR). Settings and Design: Prospective study. Methods: Retina tissues were separated from the donor/ enucleated eyes received in the eye bank within 24 h of death (n = 15) and within an hour from OR (n = 3), respectively, and stored immediately at ‑80 degree. RNA was isolated using trizol, and the quantity and quality were assessed using Qubit and agarose gel electrophoresis, respectively. QPCR was performed for measuring the expression of different retinal‑specific genes. The cellular viability of the retina was assessed by establishing explant primary cell cultures. Statistical Analysis: The data were calculated as an average of normalised Ct values ± standard error of the mean. Results: RNA obtained from cadaveric tissues despite being partially degraded showed a uniform strong gene expression of several retinal‑specific genes such as PAX6, RHO, TUBB3, CRX, and ALDH1L1. The primary cultures established from cadaveric tissues showed viable cells. Conclusion: The cadaver donor tissues collected within 24 hours of death can be effectively utilized for gene expression profiling. [ABSTRACT FROM AUTHOR]