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Carcinogenesis Jun 2024In this study, we evaluated the effects of vitamin E δ-tocotrienol (DT3) and aspirin on Wnt signaling in human colon cancer stem cells (CCSCs) and in the prevention of...
In this study, we evaluated the effects of vitamin E δ-tocotrienol (DT3) and aspirin on Wnt signaling in human colon cancer stem cells (CCSCs) and in the prevention of adenoma formation in APCmin/+ mice. We found that knockdown of the adenomatous polyposis coli (APC) gene led to subsequent activation of Wnt signaling in colon epithelial cells (NCM460-APCsiRNA) and induction of β-catenin and its downstream target proteins c-MYC, cyclin D1, and survivin. When aspirin and DT3 were combined, cell growth and survival were inhibited and apoptosis was induced in colon epithelial cells and in CCSCs. However, DT3 and/or aspirin had little or no effect on control normal colon epithelial cells (NCM460-NCsiRNA). The induction of apoptosis was directly related to activation of caspase 8 and cleavage of BID to truncated BID. In addition, DT3 and/or aspirin-induced apoptosis was associated with cleaved PARP, elevated levels of cytosolic cytochrome c and BAX, and depletion of anti-apoptotic protein BCl-2 in CCSCs. The combination of aspirin and DT3 inhibited the self-renewal capacity, Wnt/β-catenin receptor activity, and expression of β-catenin and its downstream targets c-MYC, cyclin D1 and survivin in CCSCs. We also found that treatment with DT3 alone or combined with aspirin significantly inhibited intestinal adenoma formation and Wnt/ β-catenin signaling and induced apoptosis, compared to vehicle, in APCmin/+ mice. Our study demonstrated a rationale for further investigation of the combination of DT3 and aspirin for colorectal cancer prevention and therapy.
PubMed: 38877828
DOI: 10.1093/carcin/bgae041 -
Revista Espanola de Enfermedades... Jun 2024Cap polyposis is a rare disease characterized by the presence of inflammatory polyps with an adherent fibrin sheath ("cap"), in variable number and size, in the rectum...
Cap polyposis is a rare disease characterized by the presence of inflammatory polyps with an adherent fibrin sheath ("cap"), in variable number and size, in the rectum and sigmoid. It presents with tenesmus, mucous stools and rectorrhagia. There is currently no standardized treatment, having been treated empirically with aminosalicylates, oral or rectal steroids, metronidazole, H. pylori eradication therapy and infliximab with variable results. In refractory cases, endoscopic resection of polyps may be used and surgery may even be necessary. We present the case of a 36-year-old patient diagnosed in our center with cap polyposis, refractory to both pharmacological and endoscopic treatment, and therefore treatment with infliximab was decided out of indication. The case we present is the fourth case of cap polyposis treated with infliximab available in the current literature and highlights the difficulty of achieving a clinical response with pharmacological treatment, including biologic drugs such as infliximab.
PubMed: 38873995
DOI: 10.17235/reed.2024.10297/2024 -
Frontiers in Pediatrics 2024Primary ciliary dyskinesia (PCD) is considered a rare cause of chronic rhinosinusitis with nasal polyposis (CRSwNP), which is reported in 6% of children with PCD. The...
BACKGROUND
Primary ciliary dyskinesia (PCD) is considered a rare cause of chronic rhinosinusitis with nasal polyposis (CRSwNP), which is reported in 6% of children with PCD. The forms of PCD associated with the variants of the GAS8 gene identified so far seem to be linked to recurrent respiratory infections (sinusitis, otitis, and bronchiectasis) without situs inversus.
CASE PRESENTATION
We report a case of an 11-year-old girl with recurrent otitis media, productive cough, and chronic rhinosinusitis with nasal polyposis with homozygosity for a novel nonsense mutation in the GAS8.
CONCLUSION
Children with CRSwNP should be treated in a multidisciplinary manner (ENT, pulmonologist, allergist, pathologist, pediatrician, and geneticist) because nasal polyposis often hides etiologies that must be recognized.
PubMed: 38873586
DOI: 10.3389/fped.2024.1345265 -
Allergy Jun 2024
PubMed: 38864229
DOI: 10.1111/all.16186 -
Praxis May 2024For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID...
For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration.
Topics: Humans; Nasal Polyps; Asthma, Aspirin-Induced; Sinusitis; Dipyrone; Female; Middle Aged; Asthma; Male; Rhinitis; Anti-Asthmatic Agents; Diagnosis, Differential; Antibodies, Monoclonal, Humanized; Undertreatment
PubMed: 38864100
DOI: 10.23785/PRAXIS.2024.05.005 -
Clinical Cancer Research : An Official... Jun 2024Replication repair deficiency (RRD) is a pan-cancer mechanism characterized by abnormalities in the DNA mismatch repair (MMR) system due to pathogenic variants in the...
Replication repair deficiency (RRD) is a pan-cancer mechanism characterized by abnormalities in the DNA mismatch repair (MMR) system due to pathogenic variants in the PMS2, MSH6, MSH2 or MLH1 genes, and/ or in the polymerase-proofreading genes, POLE and POLD1. RRD predisposition syndromes [constitutional MMR deficiency (CMMRD), Lynch, polymerase-proofreading associated polyposis (PPAP)] share overlapping phenotypic and biological characteristics. Moreover, cancers stemming from germline defects of one mechanism can acquire somatic defects in another, leading to complete RRD. Here we describe the recent advances in the diagnostics, surveillance, and clinical management for children with RRD syndromes. For patients with CMMRD, new data combining clinical insights and cancer genomics have revealed genotype-phenotype associations, helped in the development of novel functional assays, diagnostic guidelines, and surveillance recommendations. Recognition of non-gastrointestinal/ genitourinary malignancies, particularly aggressive brain tumors, in select children with Lynch and PPAP syndromes harbouring an RRD biology have led to new management considerations. Additionally, universal hypermutation and microsatellite instability have allowed immunotherapy to be a paradigm shift in the treatment of RRD cancers independent of their germline etiology. These advances have also stimulated a need for expert recommendations regarding genetic counselling for these patients and their families. Future collaborative work will focus on newer technologies such as quantitative measurement of circulating tumor DNA and functional genomics to tailor surveillance and clinical care, improving immune surveillance, develop prevention strategies, and deliver these novel discoveries to resource-limited settings to maximize benefits for patients globally.
PubMed: 38860976
DOI: 10.1158/1078-0432.CCR-23-3994 -
Radiology and Oncology Jun 2024Patients with familial adenomatous polyposis (FAP) develop early colorectal adenomas and if left untreated, progression to cancer is an inevitable event. Prophylactic... (Review)
Review
BACKGROUND
Patients with familial adenomatous polyposis (FAP) develop early colorectal adenomas and if left untreated, progression to cancer is an inevitable event. Prophylactic surgery does not prevent further development of cancer in the rectal remnant, rectal cuff in patients with ileal pouch anal anastomosis (IPAA) and even on the ileal mucosa of the pouch body. The aim of this review is to assess long-term rates of cancer and adenoma development in patients with FAP after prophylactic surgery and to summarise current recommendations for endoscopic management and surveillance of these patients.
MATERIALS AND METHODS
A systematic literature search of studies from January 1946 through to June 2023 was conducted using the PRISMA checklist. The electronic database PubMed was searched.
RESULTS
Fifty-four papers involving 5010 patients were reviewed. Cancer rate in the rectal remnant was 8.8-16.7% in the western population and 37% in the eastern population. The cumulative risk of cancer 30 years after surgery was 24%. Mortality due to cancer in the rectal remnant is 1.1-11.1% with a 5-year survival rate of 55%. The adenoma rate after primary IPAA was 9.4-85% with a cumulative risk of 85% 20 years after surgery and a cumulative risk of 12% for advanced adenomas 10 years after surgery. Cumulative risk for adenomas after ileorectal anastomosis (IRA) was 85% after 5 and 100% after 10 years. Adenomas developed more frequently after stapled (33.9-57%) compared to hand-sewn (0-33%) anastomosis. We identified reports of 45 cancers in patients after IPAA of which 30 were in the pouch body and 15 in the rectal cuff or at the anastomosis.
CONCLUSIONS
There was a significant incidence of cancer and adenomas in the rectal remnant and ileal pouch of FAP patients during the long-term follow-up. Regular endoscopic surveillance is recommended, not only in IRA patients, but also in pouch patients after proctocolectomy.
Topics: Humans; Adenomatous Polyposis Coli; Proctocolectomy, Restorative; Colectomy; Adenoma; Prophylactic Surgical Procedures; Colorectal Neoplasms
PubMed: 38860690
DOI: 10.2478/raon-2024-0029 -
International Forum of Allergy &... Jun 2024Unilateral or destructive sinonasal disease should raise suspicion for tumor. Patients receiving biologic therapy for CRSwNP should be carefully selected. Tissue...
Unilateral or destructive sinonasal disease should raise suspicion for tumor. Patients receiving biologic therapy for CRSwNP should be carefully selected. Tissue diagnosis should be considered prior to starting biologics for nasal polyposis.
PubMed: 38853636
DOI: 10.1002/alr.23381 -
The Laryngoscope Jun 2024The aim of this study is to investigate the impact of septal perforation (SP) on quality of life (QoL). SP is compared to the general population and patients with...
OBJECTIVE
The aim of this study is to investigate the impact of septal perforation (SP) on quality of life (QoL). SP is compared to the general population and patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) using the Sino-Nasal Outcome Test 22 (SNOT-22).
METHODS
Prospective single-center study in a referral Rhinology Unit from January 2014 to March 2023.
RESULTS
A total of 392 patients were included in three groups: controls (n = 141), CRSwNP (n = 118), and SP (n = 133). The mean score of the SNOT-22 was significantly higher in the CRSwNP group (42.4, SD = 24.4) and SP (46.5, SD = 22) compared to the control group (6.2, SD = 8.4). Scores by either items or domains were significantly higher in the CRSwNP and SP groups compared to the control group. There were no significant differences in the mean SNOT-22 between the CRSwNP and SP groups (p = 0.26; 95% CI -1.68-9.99). Domain-specific analysis of overall SNOT-22 scores revealed that patients with SP experienced higher levels of disturbances in sleep, function, and psychological domains (p ≤ 0.001).
CONCLUSION
SP produces a negative impact on QoL similar to CRSwNP. Moreover, sleep, psychological, and function domains are significantly worse in SP. Etiology and area of SP influence nasal and emotion domain, though more studies on SP using SNOT-22 and specific questionnaires are needed.
LEVEL OF EVIDENCE
Level III Laryngoscope, 2024.
PubMed: 38850257
DOI: 10.1002/lary.31557 -
Allergy Jun 2024
PubMed: 38850227
DOI: 10.1111/all.16189