54 research outputs found
Oral Lichen Planus as a Preneoplastic Inflammatory Model
Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as “a potentially malignant disorder,” it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation
Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development
Cancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumour microenvironment, serving diverse functions in tumour progression. However, the mechanisms via which CAFs influence the anti-tumour immunity remain poorly understood. Here, using multiple tumour models and biopsies from cancer patients, we report that α-SMA+ CAFs can form immunological synapses with Foxp3+ regulatory T cells (Tregs) in tumours. Notably, α-SMA+ CAFs can phagocytose and process tumour antigens and exhibit a tolerogenic phenotype which instructs movement arrest, activation and proliferation in Tregs in an antigen-specific manner. Moreover, α-SMA+ CAFs display double-membrane structures resembling autophagosomes in their cytoplasm. Single-cell transcriptomic data showed an enrichment in autophagy and antigen processing/presentation pathways in α-SMA-expressing CAF clusters. Conditional knockout of Atg5 in α-SMA+ CAFs promoted inflammatory re-programming in CAFs, reduced Treg cell infiltration and attenuated tumour development. Overall, our findings reveal an immunosuppressive mechanism entailing the formation of synapses between α-SMA+ CAFs and Tregs in an autophagy-dependent manner
Increased expression of phosphorrylated NBS1, a key molecule of the DNA damage response machinery, is an adverse prognostic factor in patients with de novo myelodysplastic syndromes
The expression of activated forms of key proteins of the DNA damage response machinery (pNBS1, pATM and γH2AX) was assessed by means of immunohistochemistry in bone marrow biopsies of 74 patients with de novo myelodysplastic syndromes (MDS) and compared with 15 cases of de novo acute myeloid leukemia (AML) and 20 with reactive bone marrow histology. Expression levels were significantly increased in both MDS and AML, compared to controls, being higher in high-risk than in low-risk MDS. Increased pNBS1 and γH2AX expression possessed a significant negative prognostic impact for overall survival in MDS patients, whereas pNBS1 was an independent marker of poor prognosis
Recent advances in intestinal lymphomas
A large variety of lymphoma types may develop as primary intestinal
neoplasms in the small intestines or, less often, in the colorectum.
Among these are a few entities such as enteropathy-associated T-cell
lymphoma or immunoproliferative small intestinal disease that,
essentially, do not arise elsewhere than in the gastrointestinal tract.
In most instances the primary intestinal lymphomas belong to entities
that also occur in lymph nodes or other mucosal sites, and may show some
peculiar features. In the case of follicular lymphoma, important
differences exist between the classical nodal cases and the intestinal
cases, considered as a variant of the disease. It is likely that the
local intestinal mucosal microenvironment is a determinant in
influencing the pathobiological features of the disease. In this review
we will present an update on the clinical, pathological and molecular
features of the lymphoid neoplasms that most commonly involve the
intestines, incorporating recent developments with respect to their
pathobiology and classification. We will emphasize and discuss the major
differential diagnostic problems encountered in practice, including the
benign reactive or atypical lymphoid hyperplasias, indolent
lymphoproliferative disorders of T or natural killer (NK) cells, and
Epstein-Barr virus (EBV)-related lymphoproliferations
Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer.
Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide. At the time of diagnosis, more than 20% of patients already have metastatic disease. In the last 20 years, the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor, anti-BRAF and antiangiogenics. Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow, proliferate and metastasize. Many molecules are involved in this proangiogenic process, such as vascular endothelial growth factor and its receptors on endothelial cells. A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31, CD34 and CD105 antigens. Even smaller molecules, such as the microRNAs, which are small non-coding RNAs, are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis. In this review, we will discuss recent advances regarding the investigation of angiogenesis, the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+ T cells in the tumor bed. Furthermore, we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer
Oral lichen planus as a preneoplastic inflammatory model. Journal of biomedicine & biotechnology 2012
Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as "a potentially malignant disorder," it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation
Simultaneous occurrence of Warthin-like papillary carcinoma and lymphoma of the mucosa associated lymphoid tissue in Hashimoto thyroiditis
Transforming Growth Factor-beta 1/Smad Signaling in Glomerulonephritis and Its Association with Progression to Chronic Kidney Disease
Introduction: Transforming growth factor-beta 1 (TGF-beta 1) is a
multifunctional cytokine, with diverse roles in fibrosis and
inflammation, which acts through Smad signaling in renal pathology. We
intended to investigate the expression of TGF-beta/Smad signaling in
glomerulonephritis (GN) and to assess its role as risk factor for
progression to chronic kidney disease (CKD). Methods: We evaluated the
immunohistochemical expression of TGF-beta 1, phosphorylated Smad3
(pSmad3), and Smad7 semiquantitatively and quantitatively using
computerized image analysis program in different compartments of 50
renal biopsies with GN, and the results were statistically analyzed with
clinicopathological parameters. We also examined the associations among
their expressions, the impact of their co-expression, and their role in
progression to CKD. Results: TGF-beta 1 expression correlated positively
with segmental glomerulosclerosis (p= 0.025) and creatinine level at
diagnosis (p = 0.002), while pSmad3 expression with interstitial
inflammation (p = 0.024). In glomerulus, concomitant expressions of high
Smad7 and medium pSmad3 were observed to be correlated with renal
inflammation, such as cellular crescent (p = 0.011), intense
interstitial inflammation (p = 0.029), and lower serum complement (C) 3
(p = 0.028) and C4 (p = 0.029). We also reported a significant
association between pSmad3 expression in glomerular endothelial cells of
proliferative GN (p = 0.045) and in podocytes of nonproliferative GN (p
= 0.005). Finally, on multivariate Cox-regression analysis, TGF-beta 1
expression (hazard ratio = 6.078; 95% confidence interval:
1.168-31.627; p = 0.032) was emerged as independent predictor for CKD.
Discussion/Conclusion: TGF-beta 1/Smad signaling is upregulated with
specific characteristics in different forms of GN. TGF-beta 1 expression
is indicated as independent risk factor for progression to CKD, while
specific co-expression pattern of pSmad3 and Smad7 in glomerulus is
correlated with renal inflammation. (C) 2021 S. Karger AG, Base
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