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CA: a Cancer Journal For Clinicians Jan 2023Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor,... (Review)
Review
Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.
Topics: Humans; Carcinoma; Maxillary Sinus Neoplasms; Melanoma; Nasal Cavity; Nose Neoplasms; Paranasal Sinuses
PubMed: 35916666
DOI: 10.3322/caac.21752 -
Cells Sep 2019The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of... (Review)
Review
The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma.
Topics: Animals; Biomarkers, Tumor; Humans; Neoplasms; RNA, Long Noncoding
PubMed: 31480503
DOI: 10.3390/cells8091015 -
Journal of Hematology & Oncology Oct 2021Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (ST) and hematological malignancies. We summarized the CD47-related clinical... (Review)
Review
Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (ST) and hematological malignancies. We summarized the CD47-related clinical research and analyzed the research trend both in the USA and in China. As of August 28, 2021, there are a total 23 related therapeutic agents with 46 clinical trials in the NCT registry platform. Among these trials, 29 are in ST, 14 in hematological malignancies and 3 in both solid tumor and hematological malignancy. The ST include gastric cancer, head and neck squamous cell carcinoma and leiomyosarcoma, while the hematological malignancies include non-Hodgkin's lymphoma, acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and chronic myeloid leukemia. Majority of the CD47-related clinical trials are at the early phases, such as 31 at phase I, 14 at phase II and 1 at phase III in the USA and 9, 6, 1, in China, respectively. The targets and spectrums of mechanism of action include 26 with mono-specific and 20 with bi-specific targets in the USA and 13 with mono-specific and 3 with bi-specific targets in China. The new generation CD47 antibodies have demonstrated promising results, and it is highly hopeful that some candidate agents will emerge and make into clinical application to meet the urgent needs of patients.
Topics: Animals; Antineoplastic Agents, Immunological; CD47 Antigen; China; Clinical Trials as Topic; Drug Development; Humans; Immunotherapy; Neoplasms; United States
PubMed: 34717705
DOI: 10.1186/s13045-021-01197-w -
Nature Reviews. Cancer May 2020Haematological malignancies were previously thought to be driven solely by genetic or epigenetic lesions within haematopoietic cells. However, the niches that maintain... (Review)
Review
Haematological malignancies were previously thought to be driven solely by genetic or epigenetic lesions within haematopoietic cells. However, the niches that maintain and regulate daily production of blood and immune cells are now increasingly being recognized as having an important role in the pathogenesis and chemoresistance of haematological malignancies. Within haematopoietic cells, the accumulation of a small number of recurrent mutations initiates malignancy. Concomitantly, specific alterations of the niches, which support haematopoietic stem cells and their progeny, can act as predisposition events, facilitating mutant haematopoietic cell survival and expansion as well as contributing to malignancy progression and providing protection of malignant cells from chemotherapy, ultimately leading to relapse. In this Perspective, we summarize our current understanding of the composition and function of the specialized haematopoietic niches of the bone marrow during health and disease. We discuss disease mechanisms (rather than malignancy subtypes) to provide a comprehensive description of key niche-associated pathways that are shared across multiple haematological malignancies. These mechanisms include primary driver mutations in bone marrow niche cells, changes associated with increased hypoxia, angiogenesis and inflammation as well as metabolic reprogramming by stromal niche cells. Consequently, remodelling of bone marrow niches can facilitate immune evasion and activation of survival pathways favouring malignant haematopoietic cell maintenance, defence against excessive reactive oxygen species and protection from chemotherapy. Lastly, we suggest guidelines for the handling and biobanking of patient samples and analysis of the niche to ensure that basic research identifying therapeutic targets can be more efficiently translated to the clinic. The hope is that integrating knowledge of how bone marrow niches contribute to haematological disease predisposition, initiation, progression and response to therapy into future clinical practice will likely improve the treatment of these disorders.
Topics: Animals; Bone Marrow Cells; Hematologic Neoplasms; Hematopoietic Stem Cells; Humans; Neoplastic Stem Cells
PubMed: 32112045
DOI: 10.1038/s41568-020-0245-2 -
Annals of the Rheumatic Diseases Aug 2023To estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi)... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate.
METHODS
Systematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool.
RESULTS
In 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data.
CONCLUSIONS
JAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons.
PROSPERO REGISTRATION NUMBER
CRD42022362630.
Topics: Adult; Humans; Methotrexate; Janus Kinase Inhibitors; Antirheumatic Agents; Arthritis, Rheumatoid; Neoplasms
PubMed: 37247942
DOI: 10.1136/ard-2023-224049 -
International Journal of Molecular... Dec 2019Hypoxia represents a frequent player in a number of malignancies, contributing to the development of the neoplastic disease. This review will discuss the means by which... (Review)
Review
Hypoxia represents a frequent player in a number of malignancies, contributing to the development of the neoplastic disease. This review will discuss the means by which hypoxia powers the mechanisms behind cancer progression, with a majority of examples from lung cancer, the leading malignancy in terms of incidence and mortality rates (the frequent reference toward lung cancer is also for simplification purposes and follow up of the global mechanism in the context of a disease). The effects induced by low oxygen levels are orchestrated by hypoxia-inducible factors (HIFs) which regulate the expression of numerous genes involved in cancer progression. Hypoxia induces epithelial-to-mesenchymal transition (EMT) and metastasis through a complex machinery, by mediating various pathways such as TGF-β, PI3k/Akt, Wnt, and Jagged/Notch. Concomitantly, hypoxic environment has a vast implication in angiogenesis by stimulating vessel growth through the HIF-1α/VEGF axis. Low levels of oxygen can also promote the process through several other secondary factors, including ANGPT2, FGF, and HGF. Metabolic adaptations caused by hypoxia include the Warburg effect-a metabolic switch to glycolysis-and GLUT1 overexpression. The switch is achieved by directly increasing the expression of numerous glycolytic enzymes that are isoforms of those found in non-malignant cells.
Topics: Basic Helix-Loop-Helix Transcription Factors; Epithelial-Mesenchymal Transition; Humans; Hypoxia; Neoplasm Proteins; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 31817513
DOI: 10.3390/ijms20246140 -
Cancer Communications (London, England) Nov 2022Reversible, spatial, and temporal regulation of metabolic reprogramming and epigenetic homeostasis are prominent hallmarks of carcinogenesis. Cancer cells reprogram... (Review)
Review
Reversible, spatial, and temporal regulation of metabolic reprogramming and epigenetic homeostasis are prominent hallmarks of carcinogenesis. Cancer cells reprogram their metabolism to meet the high bioenergetic and biosynthetic demands for vigorous proliferation. Epigenetic dysregulation is a common feature of human cancers, which contributes to tumorigenesis and maintenance of the malignant phenotypes by regulating gene expression. The epigenome is sensitive to metabolic changes. Metabolism produces various metabolites that are substrates, cofactors, or inhibitors of epigenetic enzymes. Alterations in metabolic pathways and fluctuations in intermediate metabolites convey information regarding the intracellular metabolic status into the nucleus by modulating the activity of epigenetic enzymes and thus remodeling the epigenetic landscape, inducing transcriptional responses to heterogeneous metabolic requirements. Cancer metabolism is regulated by epigenetic machinery at both transcriptional and post-transcriptional levels. Epigenetic modifiers, chromatin remodelers and non-coding RNAs are integral contributors to the regulatory networks involved in cancer metabolism, facilitating malignant transformation. However, the significance of the close connection between metabolism and epigenetics in the context of cancer has not been fully deciphered. Thus, it will be constructive to summarize and update the emerging new evidence supporting this bidirectional crosstalk and deeply assess how the crosstalk between metabolic reprogramming and epigenetic abnormalities could be exploited to optimize treatment paradigms and establish new therapeutic options. In this review, we summarize the central mechanisms by which epigenetics and metabolism reciprocally modulate each other in cancer and elaborate upon and update the major contributions of the interplays between epigenetic aberrations and metabolic rewiring to cancer initiation and development. Finally, we highlight the potential therapeutic opportunities for hematological malignancies and solid tumors by targeting this epigenetic-metabolic circuit. In summary, we endeavored to depict the current understanding of the coordination between these fundamental abnormalities more comprehensively and provide new perspectives for utilizing metabolic and epigenetic targets for cancer treatment.
Topics: Humans; Epigenesis, Genetic; Epigenomics; Neoplasms; Carcinogenesis; DNA Methylation
PubMed: 36266736
DOI: 10.1002/cac2.12374 -
Rheumatic Diseases Clinics of North... Aug 2020Individuals with scleroderma have an increased risk of cancer compared with the general population. This heightened risk may be from chronic inflammation and tissue... (Review)
Review
Individuals with scleroderma have an increased risk of cancer compared with the general population. This heightened risk may be from chronic inflammation and tissue damage, malignant transformation provoked by immunosuppressive therapies, or a common inciting factor. In unique subsets of patients with scleroderma, there is a close temporal relationship between the onset of cancer and scleroderma, suggesting cancer-induced autoimmunity. This article discusses the potential mechanistic links between cancer and scleroderma, the serologic and clinical risk factors associated with increased cancer risk in patients with scleroderma, and implications for cancer screening.
Topics: Early Detection of Cancer; Humans; Neoplasms; Scleroderma, Systemic
PubMed: 32631603
DOI: 10.1016/j.rdc.2020.03.002 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021We review the current research literature on treatment behaviour for neoplasms of the female genital tract during pregnancy. Guidelines for clinical management of... (Review)
Review
We review the current research literature on treatment behaviour for neoplasms of the female genital tract during pregnancy. Guidelines for clinical management of cervical cancer, ovarian tumours, and vulvar cancer are presented both regarding gynaecological oncologic treatment and obstetrics. Cervical cancer is the most common malignant tumour of the female genitalia during pregnancy due to the high incidence of this neoplasm in developing countries, including Bulgaria, on the one hand, and on the other, it affects women of reproductive age. Treatment algorithms depending on various factors - gestational age, stage of the disease, tumour lesion size, and presence of pelvic lymph node metastases, are presented. Ovarian tumours are classified into benign, borderline malignant, and malignant tumours. The latter, in turn, are divided into early and advanced stages, as well as epithelial and non-epithelial tumours, which can be detected at different stages of pregnancy.
Topics: Female; Genital Neoplasms, Female; Humans; Lymph Nodes; Lymphatic Metastasis; Ovarian Neoplasms; Pregnancy; Uterine Cervical Neoplasms
PubMed: 34537754
DOI: No ID Found -
Archives of Pathology & Laboratory... Jun 2018- Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma. (Review)
Review
CONTEXT
- Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma.
OBJECTIVE
- To provide a review of non-asbestos causes for malignant mesothelioma.
DATA SOURCES
- Review of relevant published literature via PubMed and other search engines.
CONCLUSIONS
- Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 ( BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).
Topics: Asbestos, Serpentine; Europe; Female; Germ-Line Mutation; Humans; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Nanotubes, Carbon; North America; Peritoneal Neoplasms; Pleural Neoplasms; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Zeolites
PubMed: 29480760
DOI: 10.5858/arpa.2017-0365-RA