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International Journal of Molecular... Sep 2019MultiDrug resistance (MDR) is a complex phenomenon responsible for multiple cross-resistance towards structurally unrelated drugs and it characterizes almost 70% of...
MultiDrug resistance (MDR) is a complex phenomenon responsible for multiple cross-resistance towards structurally unrelated drugs and it characterizes almost 70% of solid and haematological tumours at the diagnosis [...].
Topics: Antineoplastic Agents; Biomarkers; Drug Resistance, Neoplasm; Humans; Immune System; Neoplasms; Neoplastic Stem Cells
PubMed: 31561494
DOI: 10.3390/ijms20194783 -
British Journal of Cancer Jan 2021Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract... (Review)
Review
Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours. We also present a list of challenges in treating metastatic disease with immunotherapy that must be considered in order to move laboratory observations into clinical practice and maximise patient benefit.
Topics: Animals; Humans; Immunotherapy; Neoplasm Metastasis; Neoplasms
PubMed: 33262520
DOI: 10.1038/s41416-020-01160-5 -
Asian Pacific Journal of Cancer... Mar 2018Osteopontin (OPN) is a glycoprotein involved in regulation of various influences on tumor progression, such as cellular proliferation, apoptosis, angiogenesis, and... (Review)
Review
Osteopontin (OPN) is a glycoprotein involved in regulation of various influences on tumor progression, such as cellular proliferation, apoptosis, angiogenesis, and metastasis. Vascular endothelial growth factor (VEGF) is a secreted molecule supporting angiogenesis in various cancers through activation of the PI3K/AKT/ERK1/2 pathway. OPN and VEGF have a number of isoforms with various activities. In spite of the well-defined association between OPN and VEGF isoform expression and cure rate for solid tumors, there is a scarcity of information as to any association in leukemia. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that OPN and VEGF isoform expression levels may impact on chemoresistance and relapse in leukemia the same as in solid tumors. Hence, the aim of our review was to explain relationships between OPN and VEGF isoforms and angiogenesis and related pathways in chemoresistance of leukemia and solid tumors. Our findings demonstrated that OPNb and OPNc alongside with VEGF isoforms and other gene pathways are involved in angiogenesis and also might promote chemoresistance and even recurrence in leukemia and solid tumors. To sum up, targeting OPN isoforms, particularly b and c, might be a novel therapeutic strategy for the treatment of leukemia as well as solid tumors.
Topics: Alternative Splicing; Drug Resistance, Neoplasm; Humans; Leukemia; Neoplasms; Neovascularization, Pathologic; Osteopontin; Protein Isoforms
PubMed: 29580029
DOI: 10.22034/APJCP.2018.19.3.615 -
Oncogene Oct 2015Pediatric solid tumors are remarkably diverse in their cellular origins, developmental timing and clinical features. Over the last 5 years, there have been significant... (Review)
Review
Pediatric solid tumors are remarkably diverse in their cellular origins, developmental timing and clinical features. Over the last 5 years, there have been significant advances in our understanding of the genetic lesions that contribute to the initiation and progression of pediatric solid tumors. To date, over 1000 pediatric solid tumors have been analyzed by Next-Generation Sequencing. These genomic data provide the foundation to launch new research efforts to address one of the fundamental questions in cancer biology-why are some cells more susceptible to malignant transformation by particular genetic lesions at discrete developmental stages than others? Because of their developmental, molecular, cellular and genetic diversity, pediatric solid tumors provide an ideal platform to begin to answer this question. In this review, we highlight the diversity of pediatric solid tumors and provide a new framework for studying the cellular and developmental origins of pediatric cancer. We also introduce a new unifying concept called cellular pliancy as a possible explanation for susceptibility to cancer and the developmental origins of pediatric solid tumors.
Topics: Child; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Genomics; Humans; Mutation; Neoplasms
PubMed: 25639868
DOI: 10.1038/onc.2014.474 -
Oncogene Dec 2016The oncogene Lysosome-associated protein transmembrane-4β (LAPTM4B) gene was identified, and the polymorphism region in the 5'-UTR of this gene was certified to be... (Review)
Review
The oncogene Lysosome-associated protein transmembrane-4β (LAPTM4B) gene was identified, and the polymorphism region in the 5'-UTR of this gene was certified to be associated with tumor susceptibility. LAPTM4B-35 protein was found to be highly expressed in various solid tumors and could be a poor prognosis marker. The functions of LAPTM4B in solid tumors were also explored. It is suggested that LAPTM4B could promote the proliferation of tumor cells, boost invasion and metastasis, resist apoptosis, initiate autophagy and assist drug resistance.
Topics: Apoptosis; Cloning, Molecular; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Membrane Proteins; Neoplasm Invasiveness; Neoplasms; Oncogene Proteins; Oncogenes
PubMed: 27212036
DOI: 10.1038/onc.2016.189 -
International Journal of Molecular... Dec 2020Circulating tumor cells (CTCs) are a rare tumor cell subpopulation induced and selected by the tumor microenvironment's extreme conditions. Under hypoxia and starvation,... (Review)
Review
Circulating tumor cells (CTCs) are a rare tumor cell subpopulation induced and selected by the tumor microenvironment's extreme conditions. Under hypoxia and starvation, these aggressive and invasive cells are able to invade the lymphatic and circulatory systems. Escaping from the primary tumor, CTCs enter into the bloodstream to form metastatic deposits or re-establish themselves in cancer's primary site. Although radiotherapy is widely used to cure solid malignancies, it can promote metastasis. Radiation can disrupt the primary tumor vasculature, increasing the dissemination of CTCs. Radiation also induces epithelial-mesenchymal transition (EMT) and eliminates suppressive signaling, causing the proliferation of existent, but previously dormant, disseminated tumor cells (DTCs). In this review, we collect the results and evidence underlying the molecular mechanisms of CTCs and DTCs and the effects of radiation and hypoxia in developing these cells.
Topics: Animals; Humans; Neoplasm Invasiveness; Neoplasms; Neoplastic Cells, Circulating; Radiation Tolerance; Tumor Hypoxia
PubMed: 33339353
DOI: 10.3390/ijms21249592 -
World Journal of Gastroenterology Jul 2021Adult pancreatoblastoma is an exceptionally rare malignant tumour of the pancreas that mimics other solid cellular neoplasms of the pancreas, which may pose diagnostic... (Review)
Review
Adult pancreatoblastoma is an exceptionally rare malignant tumour of the pancreas that mimics other solid cellular neoplasms of the pancreas, which may pose diagnostic difficulties. Because of its rarity, little is known about its clinical and pathologic features. This article reviews the clinical and pathologic features of pancreatoblastoma in adults including differential diagnosis, treatment, and follow-up. Although pancreatoblastoma commonly occurs in childhood, there have now been more than 70 adult pancreatoblastomas described in the literature. There is a slight male predominance. There are no symptoms unique to pancreatoblastomas and adult patients are frequently symptomatic. The most common presenting symptom is abdominal pain. Grossly, the tumours are often large and well-circumscribed. Microscopically, pancreatoblastomas are composed of neoplastic cells with predominantly acinar differentiation and characteristic squamoid nests. These tumours are positive for trypsin, chymotrypsin, lipase, and BCL10. Loss of heterozygosity on chromosome 11p is the most common molecular alteration in pancreatoblastomas. Adult pancreatoblastomas are aggressive tumours with frequent local invasion, recurrence, and distant metastasis. Treatment consists of surgical resection. Chemotherapy and radiotherapy may have a role in the treatment of recurrent, residual, unresectable, and metastatic disease. It is important to distinguish pancreatoblastomas from morphological mimics such as acinar cell carcinomas, solid pseudopapillary neoplasms, and pancreatic neuroendocrine neoplasms.
Topics: Adult; Carcinoma, Acinar Cell; Humans; Male; Neoplasm Recurrence, Local; Pancreas; Pancreatic Neoplasms
PubMed: 34326617
DOI: 10.3748/wjg.v27.i26.4172 -
Archives of Pathology & Laboratory... Dec 2009Solid-pseudopapillary neoplasm of the pancreas is a relatively uncommon tumor. It typically affects young women, has nonspecific clinical and radiologic manifestations,... (Review)
Review
Solid-pseudopapillary neoplasm of the pancreas is a relatively uncommon tumor. It typically affects young women, has nonspecific clinical and radiologic manifestations, and can be readily diagnosed by ultrasound-guided fine-needle aspiration and histopathologic evaluation. Histologic features characteristically show loosely cohesive, relatively uniform polygonal cells surrounding delicate capillary-sized blood vessels. Other features include cytoplasmic vacuolization, finely stippled chromatin, nuclear grooving, eosinophilic hyaline globules, and degenerative changes. Almost all solid-pseudopapillary neoplasms harbor mutations in the beta-catenin gene. They stain with beta-catenin, CD10, and focally with neuroendocrine markers. Although previously considered benign, this tumor is currently considered a low-grade malignant epithelial neoplasm with low metastatic rate and high overall survival. Most patients are cured by complete surgical excision. Despite the characterization of the morphologic and molecular features of this enigmatic neoplasm, more work is needed to uncover its cell of origin and true histogenesis.
Topics: Biomarkers, Tumor; Carcinoma, Papillary; Female; Genetic Predisposition to Disease; Humans; Mutation; Pancreatic Neoplasms; Treatment Outcome; beta Catenin
PubMed: 19961258
DOI: 10.5858/133.12.1989 -
Archives of Pathology & Laboratory... Mar 2022Although most pancreatic and bile duct neoplasms are solid, mucinous cystic neoplasms and intraductal neoplasms have been increasingly recognized even when clinically... (Review)
Review
CONTEXT.—
Although most pancreatic and bile duct neoplasms are solid, mucinous cystic neoplasms and intraductal neoplasms have been increasingly recognized even when clinically silent, thanks to the increased use of sensitive imaging techniques. Cystic and intraductal neoplasms of the pancreas are often resectable and curable and constitute about 5% of all pancreatic neoplasms. Owing to their preinvasive nature and different biology, recognition of these entities remains a major priority. Mucinous cystic neoplasms are histologically and clinically distinct from other cystic pancreatic neoplasms. Pancreatic intraductal neoplasms encompass 3 major entities: intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Intraductal papillary neoplasms of bile ducts are also preinvasive mass-forming neoplasms with both similarities and differences with their pancreatic counterparts. All of these pancreatobiliary neoplasms have diverse and distinctive clinicopathologic, genetic, and prognostic variations.
OBJECTIVE.—
To review the clinical, pathologic, and molecular features of mucinous cystic and intraductal neoplasms of the pancreatobiliary tract.
DATA SOURCES.—
Literature review, diagnostic manuals, and guidelines.
CONCLUSIONS.—
This review will briefly describe well-known clinical and pathologic features and will focus on selected recently described aspects of morphology, grading, classification, and genomic alterations of cystic and intraductal neoplasms of the pancreatobiliary tract.
Topics: Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Prognosis
PubMed: 35192699
DOI: 10.5858/arpa.2021-0399-RA -
PloS One 2015Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors.
METHODS
Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS) of patients with solid tumors. Odds ratios (ORs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed.
RESULTS
A total of 3107 patients with solid tumor from 28 published studies were included in the meta-analysis. The median percentage of solid tumors with PD-L1 overexpression was 52.5%. PD-L1 overexpression was associated with worse OS at both 3 years (OR = 2.43, 95% confidence interval (CI) = 1.60 to 3.70, P < 0.0001) and 5 years (OR = 2.23, 95% CI = 1.40 to 3.55, P = 0.0008) of solid tumors. Among the tumor types, PD-L1 was associated with worse 3 year-OS of esophageal cancer, gastric cancer, hepatocellular carcinoma, and urothelial cancer, and 5 year-OS of esophageal cancer, gastric cancer and colorectal cancer.
CONCLUSIONS
These results suggest that expression of PD-L1 is associated with worse survival in solid tumors. However, the correlations between PD-L1 and prognosis are variant among different tumor types. More studies are needed to investigate the clinical value of PD-L1 expression in prognostic prediction and treatment option.
Topics: B7-H1 Antigen; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Proteins; Neoplasms; Survival Rate
PubMed: 26114883
DOI: 10.1371/journal.pone.0131403