Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desmoplastic infantile gangliogliomas (DIGs) are rare supratentorial tumors that arise in infancy. Despite the large size of these lesions, the prognosis is generally considered favorable after gross-total resection (GTR); however, in incidental cases tumor progression has been described. The authors report on a child harboring a DIG with a high-grade primitive cell population and glial differentiation. The progressive clinical course was determined by this cell component in spite of GTR and adjuvant chemotherapy. The significance of the presence of a high-grade primitive tumor component in the context of DIG is discussed.
 ...
PMID:Desmoplastic infantile ganglioglioma with a malignant course. 1835 12

Desmoplastic reaction of the stroma is a part and parcel of several malignancies. It may be seen within or at a site distant from the main tumour. Irrespective of the site of fibrosis in tumours, it portends a poor prognosis as it is generally associated with invasion and metastasis. In this report, we present a unique case of a 78-year-old male patient with clear cell renal carcinoma (CCRC) who presented with a lump in the right loin. On magnetic resonance imaging scan, the mass was arising from the middle part of the right kidney. The nephrectomy was done and specimen on examination revealed a variegated tumour with another whitish solid mass in the surrounding perirenal fat. The kidney tumour showed features of CCRC, whereas whitish mass was entirely composed of proliferating spindle cells. Therefore, the mass mimicked a second tumour not only on gross but even on microscopy. The special stains (Elastic-van Gieson, Masson-Trichrome, Periodic acid schiff's, alcian blue and mucicarmine), immunostaining (cytokeratin, vimentin, epithelial membrane antigen, smooth muscle actin, S-100, HMB-45, CD34 and CD117) patterns and ultrastructural features all, however, favoured it to be an extensive peritumoural fibrotic reaction rather than a neoplasm. The observation provokes important questions like whether the reaction in the index case is an example of tumour-induced fibrosis or is an unassociated phenomenon and, in the case of former, what are factors that govern the extent and site of fibrosis, i.e. intratumoural, peritumoural or away from the tumour. The finding may also help in further research and understanding of the role of stroma in cancer progression and developing stromal antigen-targeted therapies in CCRC.
 ...
PMID:Unusual appearance of perirenal fibrosis in renal cell carcinoma simulating a tumour. 1959 64

Desmoplastic melanoma is subclassified into pure and mixed variants with a higher rate of lymph node metastasis in the latter. Given that reasons for these biological differences are not currently known, we investigated these subtypes with techniques that included genetic and immunohistochemical analyses of 43 cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13 and 17). Immunohistochemical stains were performed with antibodies to markers of significance with respect to biological potential of nevomelanocytic proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin, SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no mutations were found in any of the cases on analyses of exons 11, 13 and 17 of the c-KIT gene (P=NS for all). For immunohistochemical analyses of pure versus mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d.=5.6) versus 28% (s.d.=12.6, P<0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases, P<0.01); nestin stained 83% (n=19/23 cases) versus 89% (16/18 cases, P=NS); clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P=NS); SOX10 87% (20/23 cases) versus 94% (17/18 cases, P=NS) and CD271 stained 61% (14/23 cases) versus 67% (12/18 cases, P=NS). Increased CD117 staining in the mixed variant suggests that alterations in the KIT protein may be involved in tumor progression. In addition, the proliferative index of the mixed variant was higher than that of the pure variant.
 ...
PMID:Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal. 2215 36

Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC stroma, but its roles there have not been studied. Here we report functions and molecular pathways of Gal1 that mediate its oncogenic properties in this setting. Genetic ablation of Gal1 in a mouse model of PDAC (EIa-myc mice) dampened tumor progression by inhibiting proliferation, angiogenesis, desmoplasic reaction and by stimulating a tumor-associated immune response, yielding a 20% increase in relative lifesplan. Cellular analyses in vitro and in vivo suggested these effects were mediated through the tumor microenvironment. Importantly, acinar-to-ductal metaplasia, a crucial step for initiation of PDAC, was found to be regulated by Gal1. Mechanistic investigations revealed that Gal1 promoted Hedgehog pathway signaling in PDAC cells and stromal fibroblasts as well as in Ela-myc tumors. Taken together, our findings establish a function for Gal1 in tumor-stroma crosstalk in PDAC and provide a preclinical rationale for Gal1 targeting as a microenvironment-based therapeutic strategy.
 ...
PMID:Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and Hedgehog signaling activation. 2481 70

Pancreatic ductal adenocarcinoma (PDAC) treatments have historically focused on targeting tumor cells directly. However, in pancreatic masses, the stroma encasing the malignant epithelial cells constitutes up to 80% to 90% of the tumor bulk. This extracellular matrix, which was previously neglected when designing cancer therapies, is now considered fundamental for tumor progression and drug delivery. Desmoplastic tissue is extensively cross-linked, resulting in tremendous tensile strength. This key pathological feature is procarcinogenic, linking PDAC and breast cancer (BC). Physical forces exerted onto cellular surfaces are detected intracellularly and transduced via biochemical messengers in a process called mechanotransduction. Mechanotransduction and tensional homeostasis are linked, with an integral role in influencing tumor growth, metastasis, and interactions with the immune system. It is essential to enhance our knowledge of these integral elements of parenchymal tumors. We aim to review the topic, with a special emphasis on desmoplastic processes and their importance in pancreatic and BC development and treatments, mindful that innovative diagnostic and therapeutic strategies cannot focus on biochemical pathways alone. We then focus on common therapeutic targets identified in both PDAC and BC models and/or patients, aiming to understand these treatments and draw similarities between the two tumors.
 ...
PMID:Desmoplasia and Biophysics in Pancreatic Ductal Adenocarcinoma: Can We Learn From Breast Cancer? 3216 49

Immune checkpoint blockade (ICB) has revolutionized cancer therapeutics. Desmoplastic malignancies, such as cholangiocarcinoma (CCA), have an abundant tumor immune microenvironment (TIME). However, to date, ICB monotherapy in such malignancies has been ineffective. Herein, we identify tumor-associated macrophages (TAMs) as the primary source of programmed death-ligand 1 (PD-L1) in human and murine CCA. In a murine model of CCA, recruited PD-L1+ TAMs facilitated CCA progression. However, TAM blockade failed to decrease tumor progression due to a compensatory emergence of granulocytic myeloid-derived suppressor cells (G-MDSCs) that mediated immune escape by impairing T cell response. Single-cell RNA sequencing (scRNA-Seq) of murine tumor G-MDSCs highlighted a unique ApoE G-MDSC subset enriched with TAM blockade; further analysis of a human scRNA-Seq data set demonstrated the presence of a similar G-MDSC subset in human CCA. Finally, dual inhibition of TAMs and G-MDSCs potentiated ICB. In summary, our findings highlight the therapeutic potential of coupling ICB with immunotherapies targeting immunosuppressive myeloid cells in CCA.
 ...
PMID:Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma. 3266 98