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Genes Mar 2021Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the... (Review)
Review
Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the gene are the most common cause of KS and account for up to 75% of patients. Variants in cause up to 5% of cases (X-linked dominant inheritance), while the etiology of about 20% of cases remains unknown. Current KS diagnostic criteria include hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphism and confirmed pathogenic/likely pathogenic variant in or . Care for KS patients includes the control of physical and psychomotor development during childhood, rehabilitation and multi-specialist care. This paper reviews the current clinical knowledge, provides molecular and scientific links and sheds light on the treatment of Kabuki syndrome individuals.
Topics: Abnormalities, Multiple; DNA-Binding Proteins; Face; Hematologic Diseases; Histone Demethylases; Humans; Mutation; Neoplasm Proteins; Phenotype; Vestibular Diseases
PubMed: 33805950
DOI: 10.3390/genes12040468 -
Science Advances Feb 2023Enhancing the intracellular labile iron pool (LIP) represents a powerful, yet untapped strategy for driving ferroptotic death of cancer cells. Here, we show that NRF2...
Enhancing the intracellular labile iron pool (LIP) represents a powerful, yet untapped strategy for driving ferroptotic death of cancer cells. Here, we show that NRF2 maintains iron homeostasis by controlling HERC2 (E3 ubiquitin ligase for NCOA4 and FBXL5) and VAMP8 (mediates autophagosome-lysosome fusion). knockout cells have low expression, leading to a simultaneous increase in ferritin and NCOA4 and recruitment of apoferritin into the autophagosome. knockout cells also have low expression, which leads to ferritinophagy blockage. Therefore, deletion of results in apoferritin accumulation in the autophagosome, an elevated LIP, and enhanced sensitivity to ferroptosis. Concordantly, NRF2 levels correlate with HERC2 and VAMP8 in human ovarian cancer tissues, as well as ferroptosis resistance in a panel of ovarian cancer cell lines. Last, the feasibility of inhibiting NRF2 to increase the LIP and kill cancer cells via ferroptosis was demonstrated in preclinical models, signifying the impact of NRF2 inhibition in cancer treatment.
Topics: Humans; Female; Ferroptosis; NF-E2-Related Factor 2; Apoferritins; Ovarian Neoplasms; Iron; Homeostasis; Ubiquitin-Protein Ligases; R-SNARE Proteins
PubMed: 36724221
DOI: 10.1126/sciadv.ade9585 -
Signal Transduction and Targeted Therapy May 2020Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases,...
Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including cancer. Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that Ca/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis. Taken together, our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca/CaM-dependent ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung cancer treatment.
Topics: Animals; Bibenzyls; Calcium; Calcium Signaling; Calmodulin; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dendrobium; Female; Ferroptosis; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins; Phenol; Plant Extracts
PubMed: 32382060
DOI: 10.1038/s41392-020-0149-3 -
Veterinary and Comparative Oncology Dec 2022One of the primary objectives of the Oncology Pathology Working Group (OPWG) is for oncologists and pathologists to collaboratively generate consensus documents to... (Review)
Review
One of the primary objectives of the Oncology Pathology Working Group (OPWG) is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for veterinary oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for the diagnosis of, and histopathologic prognostication for, canine cutaneous and oral/lip melanocytic neoplasms, suggest guidelines for reporting, provide recommendations for clinical interpretation, and discuss future directions. This document represents the opinions of the working group and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists, American College of Veterinary Internal Medicine or the Veterinary Cancer Society.
Topics: Dogs; Animals; Consensus; Dog Diseases; Medical Oncology; Neoplasms; Pathology, Veterinary
PubMed: 35522017
DOI: 10.1111/vco.12827 -
Nature Sep 2022Medulloblastoma, a malignant childhood cerebellar tumour, segregates molecularly into biologically distinct subgroups, suggesting that a personalized approach to...
Medulloblastoma, a malignant childhood cerebellar tumour, segregates molecularly into biologically distinct subgroups, suggesting that a personalized approach to therapy would be beneficial. Mouse modelling and cross-species genomics have provided increasing evidence of discrete, subgroup-specific developmental origins. However, the anatomical and cellular complexity of developing human tissues-particularly within the rhombic lip germinal zone, which produces all glutamatergic neuronal lineages before internalization into the cerebellar nodulus-makes it difficult to validate previous inferences that were derived from studies in mice. Here we use multi-omics to resolve the origins of medulloblastoma subgroups in the developing human cerebellum. Molecular signatures encoded within a human rhombic-lip-derived lineage trajectory aligned with photoreceptor and unipolar brush cell expression profiles that are maintained in group 3 and group 4 medulloblastoma, suggesting a convergent basis. A systematic diagnostic-imaging review of a prospective institutional cohort localized the putative anatomical origins of group 3 and group 4 tumours to the nodulus. Our results connect the molecular and phenotypic features of clinically challenging medulloblastoma subgroups to their unified beginnings in the rhombic lip in the early stages of human development.
Topics: Animals; Cell Lineage; Cerebellar Neoplasms; Cerebellum; Humans; Medulloblastoma; Metencephalon; Mice; Neurons; Prospective Studies
PubMed: 36131015
DOI: 10.1038/s41586-022-05208-9 -
JAMA Dermatology Apr 2016To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically.
OBJECTIVE
To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC.
DATA SOURCES
Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database's inception to May 14, 2015.
STUDY SELECTION
Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale.
MAIN OUTCOMES AND MEASURES
A priori outcomes were recurrence, metastasis, and DSD.
RESULTS
Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2 mm (risk ratio [RR], 9.64; 95% CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95% CI, 4.17-13.88), Breslow thickness exceeding 6 mm (RR, 7.13; 95% CI, 3.04-16.72), perineural invasion (RR, 4.30; 95% CI, 2.80-6.60), diameter exceeding 20 mm (RR, 3.22; 95% CI, 1.91-5.45), location on the temple (RR, 3.20; 95% CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95% CI, 1.72-4.14). Significant risk factors for metastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95% CI, 3.59-34.97), Breslow thickness exceeding 2 mm (RR, 10.76; 95% CI, 2.55-45.31), Breslow thickness exceeding 6 mm (RR, 6.93; 95% CI, 4.02-11.94), diameter exceeding 20 mm (RR, 6.15; 95% CI, 3.56-10.65), poor differentiation (RR, 4.98; 95% CI, 3.30-7.49), perineural invasion (RR, 2.95; 95% CI, 2.31-3.75), immunosuppression (RR, 1.59; 95% CI, 1.07-2.37), and location on the temple (RR, 2.82; 95% CI, 1.72-4.63), ear (RR, 2.33; 95% CI, 1.67-3.23), or lip (RR, 2.28; 95% CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20 mm (RR, 19.10; 95% CI, 5.80-62.95), poor differentiation (RR, 5.65; 95% CI, 1.76-18.20), location on the ear (RR, 4.67; 95% CI, 1.28-17.12) or lip (RR, 4.55; 95% CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95% CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95% CI, 3.10-5.32). Evidence quality was considered low to moderate.
CONCLUSIONS AND RELEVANCE
Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20 mm is associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.
Topics: Carcinoma, Squamous Cell; Genetic Predisposition to Disease; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Recurrence, Local; Risk Factors; Skin Neoplasms
PubMed: 26762219
DOI: 10.1001/jamadermatol.2015.4994 -
Nature Communications Apr 2023Targeting tumour immunosuppressive microenvironment is a crucial strategy in immunotherapy. However, the critical role of the tumour lymph node (LN) immune...
Targeting tumour immunosuppressive microenvironment is a crucial strategy in immunotherapy. However, the critical role of the tumour lymph node (LN) immune microenvironment (TLIME) in the tumour immune homoeostasis is often ignored. Here, we present a nanoinducer, NIL-IM-Lip, that remodels the suppressed TLIME via simultaneously mobilizing T and NK cells. The temperature-sensitive NIL-IM-Lip is firstly delivered to tumours, then directed to the LNs following pH-sensitive shedding of NGR motif and MMP2-responsive release of IL-15. IR780 and 1-MT induces immunogenic cell death and suppress regulatory T cells simultaneously during photo-thermal stimulation. We demonstrate that combining NIL-IM-Lip with anti-PD-1 significantly enhances the effectiveness of T and NK cells, leading to greatly suppressed tumour growth in both hot and cold tumour models, with complete response in some instances. Our work thus highlights the critical role of TLIME in immunotherapy and provides proof of principle to combine LN targeting with immune checkpoint blockade in cancer immunotherapy.
Topics: Humans; Liposomes; Nanomedicine; Temperature; Neoplasms; Lymph Nodes; Tumor Microenvironment; Immunotherapy
PubMed: 37076492
DOI: 10.1038/s41467-023-38014-6 -
The Pan African Medical Journal 2021Pleomorphic adenoma is a benign mixed tumor, which is composed of myoepithelial and epithelial cells. A fibrous capsule separates these cells from the surrounding...
Pleomorphic adenoma is a benign mixed tumor, which is composed of myoepithelial and epithelial cells. A fibrous capsule separates these cells from the surrounding tissues. Pleomorphic adenoma is the most common salivary gland tumour accounting for 40-70% of all major and minor salivary gland tumours. It is also the commonest minor salivary gland benign tumours accounting for 70% of all tumours. Hard palate is the commonest site followed by upper lip, buccal mucosa, tongue, floor of mouth, retromolar trigone. This case report discusses a case of pleomorphic adenoma of hard palate in an old man after complete excision of the tumour, which was confirmed by a biopsy specimen.
Topics: Adenoma, Pleomorphic; Adult; Humans; Male; Palatal Neoplasms; Palate, Hard
PubMed: 33912316
DOI: 10.11604/pamj.2021.38.146.26508 -
Anais Brasileiros de Dermatologia 2016Plasmoacanthoma is an extremely rare verrucous tumor located on periorificial regions characterized by dense dermal plasmacytic infiltrates. Some authors classify it as...
Plasmoacanthoma is an extremely rare verrucous tumor located on periorificial regions characterized by dense dermal plasmacytic infiltrates. Some authors classify it as a form of reactive plasma cell proliferation which represents a heterogeneous spectrum of mucocutaneous disorders. These plasma cell proliferations have been considered to be a benign immunologic inflammatory reaction to known or unknown stimuli. However, the etiology of plasmoacanthoma remains highly speculative. We report the case of a 40-year-old woman who presented with a lobulated warty lesion affecting the lower lip. Biopsy from the lesion was compatible with plasmoacanthoma, which remains an underreported disease in the dermatology literature.
Topics: Acanthoma; Adult; Biopsy; Cell Proliferation; Dermis; Female; Humans; Immunohistochemistry; Lip; Lip Neoplasms; Mouth Mucosa; Plasma Cells; Skin Neoplasms
PubMed: 28300919
DOI: 10.1590/abd1806-4841.20164673