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1.
Artigo em Inglês | MEDLINE | ID: mdl-38808735

RESUMO

PURPOSE: Chemotherapy is one of the common treatments in cancer management. However, chemotherapy-induced cognitive impairment (CICI) is one notable side effect that can greatly impact a patient's quality of life. Literature on CICI in gastrointestinal (GI) cancers are few and inconsistent. This review aims to identify the methodological differences in such studies. METHODS: A systematic search was performed in four electronic databases. All peer-reviewed primary literature published in English that evaluated cognitive-related functioning scores related to chemotherapy in GI cancer patients were included. Information about each study such as CICI findings, study limitations, methodology, and sample characteristics was extracted and synthesized. RESULTS: A total of 19 studies were included. Evidence of CICI was found in 50.0% (8 of 16) and 62.5% (5 of 8) studies that used objective and subjective measures, respectively. Methodological differences such as groups used for comparison, instruments used, and assessment from the length of time since chemotherapy were highlighted between studies that did and did not find evidence of CICI. CONCLUSIONS: This review suggests that the mixed findings can be attributed to the heterogeneous methodologies adopted in the evaluation of CICI in this field. IMPLICATIONS FOR CANCER SURVIVORS: Further studies are necessary to establish the presence and chronicity of CICI, and in which groups of patients to facilitate targeted interventions and treatments.

2.
Int J Clin Oncol ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709424

RESUMO

BACKGROUND: Lymph node metastasis (LNM) occurs in 20-25% of patients with T2 colorectal cancer (CRC). Identification of risk factors for LNM in T2 CRC may help identify patients who are at low risk and thereby potential candidates for endoscopic full-thickness resection. We examined risk factors for LNM in T2 CRC with the goal of establishing further criteria of the indications for endoscopic resection. METHODS: MEDLINE, CENTRAL, and EMBASE were systematically searched from inception to November 2023. Studies that investigated the association between the presence of LNM and the clinical and pathological factors of T2 CRC were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Certainty of evidence (CoE) was assessed using the GRADE approach. RESULTS: Fourteen studies (8349 patients) were included. Overall, the proportion of LNM was 22%. The meta-analysis revealed that the presence of lymphovascular invasion (OR, 5.5; 95% CI 3.7-8.3; high CoE), high-grade tumor budding (OR, 2.4; 95% CI 1.5-3.7; moderate CoE), poor differentiation (OR, 2.2; 95% CI 1.8-2.7; moderate CoE), and female sex (OR, 1.3; 95% CI 1.1-1.7; high CoE) were associated with LNM in T2 CRC. Lymphatic invasion (OR, 5.0; 95% CI 3.3-7.6) was a stronger predictor of LNM than vascular invasion (OR, 2.4; 95% CI 2.1-2.8). CONCLUSIONS: Lymphovascular invasion, high-grade tumor budding, poor differentiation, and female sex were risk factors for LNM in T2 CRC. Endoscopic resection of T2 CRC in patients with very low risk for LNM may become an alternative to conventional surgical resection. TRIAL REGISTRATION: PROSPERO, CRD42022316545.

3.
J Cancer Surviv ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627293

RESUMO

OBJECTIVE: Patient-reported outcome measures (PROM) are frequently adopted to evaluate colorectal cancer (CRC) care, but the use of patient-reported experience measures (PREM) appears to be underdeveloped and not widely validated. This scoping review aims to understand the contexts for deployment of PREMs in CRC care, reliability of measures, gaps in current use of PREMs, and how PREMs are associated with PROMs when deployed together. METHODS: Four scientific databases (PubMed, CINAHL, PsycINFO, Scopus) were systematically searched from January 2011 to December 2023. Observational or interventional studies involving quantitative or mixed methodology with samples consisting CRC patients undergoing screening, treatment, or cancer surveillance and utilizing at least one PREM as an exposure or outcome were included. RESULTS: The initial search resulted in 10,400 records. Only 13 relevant studies (consisting of 17,105 participants) met the eligibility criteria. Utilization of PREMs was heterogenous across our sample and the CRC care continuum, and about half of the studies (53.8%) evaluated the relationship between PREMs and PROMs. PREM usage across the CRC care continuum largely focused on treatment/survivorship. Better care experience was positively associated with improved patient-reported outcomes. CONCLUSIONS: Future work in CRC PREM development should focus on (1) establishing validated measures that aim to either capture disease/treatment-specific granularity or capitalize on applicability across care settings, (2) localizing novel or existing PREMs to consider different cultural contexts in healthcare, and (3) benchmarking associations between PREMs, PROMs, and other outcomes of interest. IMPLICATIONS FOR CANCER SURVIVORS: Individuals progressing through the CRC care continuum often undergo a multitude of procedures from detection and diagnosis to treatment and surveillance. The establishment of validated PREMs specific to CRC would help to benchmark and further improve the quality of care received-which should translate to better patient-reported outcomes-and serve as process indicators for institutions and providers to maintain rigorous health service delivery standard for CRC survivors.

4.
J Immunother Cancer ; 12(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508656

RESUMO

BACKGROUND: The effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this study investigates the potential of tumor-associated circular RNAs (circRNAs) as an alternative source of neoepitopes in CRC. METHODS: Tumor-associated circRNAs in CRC were identified using the MiOncoCirc database and ribo-depletion RNA sequencing of paired clinical normal and tumor samples. Candidate circRNA expression was validated by quantitative real-time PCR (RT-qPCR) using divergent primers. TransCirc database was used for translation prediction. Human leukocyte antigen binding affinity of open reading frames from potentially translatable circRNA was predicted using pVACtools. Strong binders from messenger RNA-encoded proteins were excluded using BlastP. The immunogenicity of the candidate antigens was functionally validated through stimulation of naïve CD8+ T cells against the predicted neoepitopes and subsequent analysis of the T cells through enzyme-linked immunospot (ELISpot) assay, intracellular cytokine staining (ICS) and granzyme B (GZMB) reporter. The cytotoxicity of T cells trained with antigen peptides was further tested using patient-derived organoids. RESULTS: We identified a neoepitope from circRAPGEF5 that is upregulated in CRC tumor samples from MiOncoCirc database, and two neoepitopes from circMYH9, which is upregulated across various tumor samples from our matched clinical samples. The translation potential of candidate peptides was supported by Clinical Proteomic Tumor Analysis Consortium database using PepQuery. The candidate peptides elicited antigen-specific T cells response and expansion, evidenced by various assays including ELISpot, ICS and GZMB reporter. Furthermore, T cells trained with circMYH9 peptides were able to specifically target and eliminate tumor-derived organoids but not match normal organoids. This observation underscores the potential of circRNAs as a source of immunogenic neoantigens. Lastly, circMYH9 was enriched in the liquid biopsies of patients with CRC, thus enabling a detection-to-vaccination treatment strategy for patients with CRC. CONCLUSIONS: Our findings underscore the feasibility of tumor-associated circRNAs as an alternative source of neoantigens for cancer vaccines targeting tumors with moderate mutation levels.


Assuntos
Vacinas Anticâncer , Neoplasias Colorretais , Humanos , RNA Circular/genética , Linfócitos T CD8-Positivos , Antígenos de Neoplasias/genética , Proteômica , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Peptídeos
5.
Am J Hosp Palliat Care ; : 10499091241231881, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324510

RESUMO

OBJECTIVES: Perceptions towards advanced care planning (ACP) amongst individuals with Ischemic Heart Disease before or after a life-threatening Acute Myocardial Infarction event is underexamined and could impact the appropriate timing for ACP advocacy. This cross-sectional study assessed awareness and intentions regarding ACP in individuals with Ischemic Heart Disease, both before and after an Acute Myocardial Infarction, and explored the motivating effect of a near-fatal Acute Myocardial Infarction event on its engagement. METHODS: This study was conducted from 24 August 2021 through 13 March 2023, whereby patients were administered a one-time questionnaire with no follow-up required. Patients with either chronic Ischemic Heart Disease (group A) or a recent Acute Myocardial Infarction event (group B) were recruited from the outpatient National University Heart Centre, Singapore. RESULTS: 101 patients (n = 51 for Group A, n = 50 for Group B) were recruited. Mean age (SD) was 59 (10.5) years and 84 were male (83.2%). Between both groups, patients in group B reported significantly higher scores on 'Lack of information' and 'Self-efficacy' domains, and had no ACP awareness nor plans of doing an ACP compared to group A. ACP awareness was the sole significant predictor of intentions of doing an ACP in the final regression model (P < .05). CONCLUSIONS: Interestingly, this study suggests that surviving a potentially life-threatening heart condition did not result in higher intention of doing an ACP. Thus, advocacy of ACP in the community should simply start by raising awareness levels widely and may not need to be focused on individuals' state of health.

6.
NPJ Precis Oncol ; 8(1): 52, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413740

RESUMO

Globally, colorectal cancer (CRC) is the third most frequently occurring cancer. Progression on to an advanced metastatic malignancy (metCRC) is often indicative of poor prognosis, as the 5-year survival rates of patients decline rapidly. Despite the availability of many systemic therapies for the management of metCRC, the long-term efficacies of these regimens are often hindered by the emergence of treatment resistance due to intratumoral and intertumoral heterogeneity. Furthermore, not all systemic therapies have associated biomarkers that can accurately predict patient responses. Hence, a functional personalised oncology (FPO) approach can enable the identification of patient-specific combinatorial vulnerabilities and synergistic combinations as effective treatment strategies. To this end, we established a panel of CRC patient-derived organoids (PDOs) as clinically relevant biological systems, of which three pairs of matched metCRC PDOs were derived from the primary sites (ptCRC) and metastatic lesions (mCRC). Histological and genomic characterisation of these PDOs demonstrated the preservation of histopathological and genetic features found in the parental tumours. Subsequent application of the phenotypic-analytical drug combination interrogation platform, Quadratic Phenotypic Optimisation Platform, in these pairs of PDOs identified patient-specific drug sensitivity profiles to epigenetic-based combination therapies. Most notably, matched PDOs from one patient exhibited differential sensitivity patterns to the rationally designed drug combinations despite being genetically similar. These findings collectively highlight the limitations of current genomic-driven precision medicine in guiding treatment strategies for metCRC patients. Instead, it suggests that epigenomic profiling and application of FPO could complement the identification of novel combinatorial vulnerabilities to target synchronous ptCRC and mCRC.

7.
Sci Rep ; 14(1): 2819, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38307921

RESUMO

Viruses are a key component of the colon microbiome, but the relationship between virome and colorectal cancer (CRC) remains poorly understood. We seek to identify alterations in the viral community that is characteristic of CRC and examine if they persist after surgery. Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for metagenomic analysis. The fecal virome of CRC patients demonstrated an increased network connectivity as compared to NC individuals. Co-exclusion of influential viruses to bacterial species associated with healthy gut status was observed in CRC, suggesting an altered virome induced a change in the healthy gut bacteriome. Network analysis revealed lower connectivity within the virome and trans-kingdom interactions in NC. After surgery, the number of strong correlations decreased for trans-kingdom and within the bacteria and virome networks, indicating lower connectivity within the microbiome. Some co-occurrence patterns between dominant viruses and bacteria were also lost after surgery, suggesting a possible return to the healthy state of gut microbiome. Microbial signatures characteristic of CRC include an altered virome besides an altered bacterial composition. Elevated viral correlations and network connectivity were observed in CRC patients relative to healthy individuals, alongside distinct changes in the cross-kingdom correlation network unique to CRC patients. Some patterns of dysbiosis persist after surgery. Future studies should seek to verify if dysbiosis truly persists after surgery in a larger sample size with microbiome data collected at various time points after surgery to explore if there is field-change in the remaining colon, as well as to examine if persistent dysbiosis correlates with patient outcomes.


Assuntos
Neoplasias Colorretais , Microbiota , Vírus , Humanos , Viroma , Disbiose/microbiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/microbiologia
8.
J Intensive Care Med ; 39(2): 153-158, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37583284

RESUMO

BACKGROUND: Surgical high dependency (SHD) allows for intermediate care provision between general ward (GW) and intensive care unit (ICU) for surgical patients but no universally accepted admission criteria exists. Unnecessary SHD admissions should be minimized to limit resource wastage and maintain spare critical care capacity. This study evaluates the utility of SHD admissions following elective laparoscopic colectomy by comparing post-operative outcomes and interventions performed between SHD and GW patients. METHODOLOGY: A retrospective review of all colorectal cancer patients who underwent elective laparoscopic colectomy in our institution between January 2019 and December 2021 was conducted. Patients converted to open surgery or admitted to IC post-operatively were excluded. Peri-operative parameters and outcomes between patients admitted to GW and SHD post-operatively were evaluated. RESULTS: The cohort comprised 393 patients. There were 153 patients (38.93%) who required SHD admission. SHD patients had higher American Society of Anesthesiology (ASA) scores, body mass index, age and intra-operative blood loss. Majority of post-operative morbidity were minor (Clavien-Dindo II or lower) in both groups and the interventions required were safely instituted in both SHD and GW. None of the patients in the cohort required inotropic or ventilatory support in the SHD. CONCLUSIONS: GW patients were "healthier" but post-operative morbidity and interventions required were similar to the SHD group. Nonetheless, treatment delays, absence of continuous monitoring, and decreased nurse-to-patient ratio may be significant for patients with limited physiological reserves. Further studies should evaluate safety and cost-effectiveness of managing high risk surgical patients in GW using continuous remote vital signs monitoring.


Assuntos
Neoplasias Colorretais , Laparoscopia , Humanos , Hospitalização , Laparoscopia/efeitos adversos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/etiologia , Colectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
9.
Eur J Surg Oncol ; 50(1): 107291, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38064864

RESUMO

BACKGROUND: Health-related quality of life (HRQOL) is an increasingly important outcome in colorectal cancer (CRC) treatment. Established thresholds for clinical importance (TCI) permit an absolute interpretation of HRQOL scores but less emphasis has been placed on whether these can be used in a predictive manner. This study aimed to examine if patients' baseline HRQOL functioning scores, subgrouped based on TCI, would significantly predict HRQOL over time. METHODS: 211 CRC patients were prospectively followed up from diagnosis to 18 months after surgery. Patients were administered the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) at each timepoint. Baseline demographic and clinical data were extracted from electronic medical records. RESULTS: Only the physical and emotional functioning scales of the EORTC QLQ-C30 were utilised with their respective TCIs (score of ≤83 for physical; ≤71 for emotional). Physical functioning was below-threshold for most patients at pre-discharge (81.77 %) and 1-month (56.48 %) before stabilising to baseline proportions by 6-month. For emotional functioning, 22.04 %-30.98 % of patients were below-threshold between baseline to 3-month, stabilising to approximately 14.00 % after 6-month. Baseline TCI subgrouping was significantly associated with change in HRQOL scores over time for both the physical (ß = 14.09, 95 % CI: 8.22, 19.97) and emotional (ß = 25.66, 95 % CI: 18.79, 32.53) functioning scales (p < 0.01). CONCLUSION: EORTC QLQ-C30 TCIs can be utilised not just to concretely identify clinically significant impairments in presenting CRC patients, but also as potential predictive tools towards more value-driven delivery of pre- and post-surgical supportive and allied healthcare.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Estudos Prospectivos , Relevância Clínica , Inquéritos e Questionários , Neoplasias Colorretais/cirurgia
10.
Acta Ophthalmol ; 102(3): e257-e271, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37786939

RESUMO

PURPOSE: During the COVID-19 pandemic, home-based and remote learning-particularly using electronic devices-was rapidly pushed out. Increased near-work, screen time exposure and lack of outdoor time are risk factors that contribute to childhood myopia, but it is difficult to adopt recommendations from prior publications as a consistent limitation in the literature is the heterogeneity of research methodology. This review seeks to systematically evaluate how observational studies published during the pandemic have quantified and measured risk factors and myopia in school-going children and adolescents. METHODS: Three scientific databases (PubMed, CINAHL, Scopus) were systematically searched from March 2020 to April 2022. Findings from relevant studies were descriptively summarised in relation to the PICOS-based objective of the review. RESULTS: The final sample of 13 studies included research from six countries and comprised 1 411 908 children and adolescents. The majority of studies (N = 10; 76.9%) used spherical equivalent refraction (SER) of -0.5 dioptres or lower as a common definition of myopia. Most studies (77.8%) measuring screen time exposure found it higher during COVID-19 compared to pre-COVID, but only one study used objective measurement of screen time. The average critical appraisal score of the sample was only 66.1%, with a considerable number of studies failing to identify and adjust for potential confounders. CONCLUSION: Future studies should consider emergent objective and validated measures of risk factors, account for potential a priori confounders and covariates and ensure more representativeness in the sociodemographic makeup of their samples.


Assuntos
COVID-19 , Miopia , Adolescente , Humanos , Criança , Pandemias , COVID-19/epidemiologia , COVID-19/complicações , Miopia/epidemiologia , Miopia/etiologia , Fatores de Risco , Refração Ocular
11.
Gut Liver ; 18(2): 218-221, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37842729

RESUMO

The current standard treatment for muscularis propria-invasive (T2) colorectal cancer is surgical colectomy with lymph node dissection. With the advent of new endoscopic resection techniques, such as endoscopic full-thickness resection or endoscopic intermuscular dissection, T2 colorectal cancer, with metastasis to 20%-25% of the dissected lymph nodes, may be the next candidate for endoscopic resection following submucosal-invasive (T1) colorectal cancer. We present a novel endoscopic treatment strategy for T2 colorectal cancer and suggest further study to establish evidence on oncologic and endoscopic technical safety for its clinical implementation.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Endoscopia , Linfonodos/patologia , Linfonodos/cirurgia , Dissecação , Metástase Linfática
12.
Psychiatry Res ; 329: 115516, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37797442

RESUMO

Self-isolation was common in the first year of COVID-19. While necessary, it also increased vulnerability to adverse mental health among elderly (i.e. aged 60 and above). This review seeks to summarise the outcomes, measures, and protective and risk factors of elderly mental health in the first year of COVID-19. Four international databases were systematically searched from inception to August 2021. Forty-five studies examining elderly mental health outcomes specific to COVID-19 were included - one was qualitative, 29 used cross-sectional quantitative methods, and 15 were longitudinal. Anxiety and depression were examined most commonly and consistently, largely with well-validated scales. Older age, female sex, poor financial status, being unmarried, high loneliness, low social engagement, low resilience and more severe pandemic measures were associated with poor elderly mental health outcomes. Ten of 13 longitudinal studies found deteriorations in elderly mental health outcomes over time. More consistent measures are needed to understand the pandemic's impact on elderly mental health. Our findings also suggest that socialising through digital mediums may not be helpful, and might even exacerbate loneliness. While the elderly are generally considered a high-risk population, higher-risk subpopulations were identified. We conclude by suggesting a multilevel approach to safeguard elderly mental health for future crises.


Assuntos
COVID-19 , Saúde Mental , Idoso , Humanos , Feminino , Estudos Transversais , Pandemias , Ansiedade/epidemiologia , Depressão/epidemiologia
14.
Medicina (Kaunas) ; 59(6)2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37374333

RESUMO

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.


Assuntos
Neoplasias Colorretais , Protectomia , Humanos , Qualidade de Vida/psicologia , Estudos Prospectivos , Saúde Mental , Neoplasias Colorretais/complicações , Inquéritos e Questionários
16.
Asian Pac J Cancer Prev ; 24(3): 889-895, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36974542

RESUMO

OBJECTIVE: The uptake of breast and cervical cancer screening services among women in Singapore remains inadequate. Little is known about how gender norms influence women's decision to undergo these screening services in a multi-ethnic Asian context. This research aimed to explore how gender-based qualitative factors influence women's decision to screen. METHODS: Qualitative data were collected using semi-structured interviews from 40 racially diverse women aged 25 and above who had visited polyclinics for their chronic disease management. Women were recruited using a purposive maximum variation sampling strategy to ensure representation of their views from the three major ethnic groups and based on inclusion criteria. Interviews were conducted either face-to-face or via telephone call. Interviews were audiotaped and lasted 30 minutes on average. Interviews were conducted until data saturation was reached. The data was transcribed and analysed thematically. RESULTS: Gender norms and gender non-concordance with the healthcare professionals did not inhibit women from undergoing breast and cervical cancer screening services to a large extent. Women were empowered and had a central role in decision-making for screening services. Healthcare initiatives such as subsidies and mobile health applications facilitated the uptake of breast and cervical cancer screening services but can be improved further. Some of the barriers reported by Malay Muslims were not dissimilar to previous qualitative studies with women in this ethnic and religious group. CONCLUSION: Gender socialisation, empowerment, and healthcare initiatives did not inhibit our study participants' decision to undergo breast and cervical cancer screening services. However, new initiatives and strengthening of the existing healthcare initiatives are needed to overcome any remnants of gender-related nuances and convert non-doers into doers.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Neoplasias do Colo do Útero , Feminino , Humanos , Programas de Rastreamento , Pesquisa Qualitativa , Singapura , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Povo Asiático , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle
17.
Nat Commun ; 14(1): 1726, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36977662

RESUMO

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles. In multiple tissues, EGFR is stabilized by TAD and DBD mutants in the cytosolic and nuclear compartments respectively. TAD mutants promote EGFR-mediated signaling by enhancing EGFR interaction with AKT via DDX31 in the cytosol. Conversely, DBD mutants maintain EGFR activity in the nucleus, by blocking EGFR interaction with the phosphatase SHP1, triggering c-Myc and Cyclin D1 upregulation. Our findings suggest that p53 mutants carrying gain-of-function, mis-sense mutations affecting two different domains form new protein complexes that promote carcinogenesis by enhancing EGFR signaling via distinctive mechanisms, exposing clinically relevant therapeutic vulnerabilities.


Assuntos
Receptores ErbB , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Transdução de Sinais , Ativação Transcricional , Fosforilação
18.
Dig Dis ; 41(4): 600-603, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36966526

RESUMO

BACKGROUND: Colonoscopy is a commonly performed procedure, but most patients will not actually be found with colorectal cancer. Subsequent face-to-face consultations to explain post-colonoscopy findings are common despite the time and cost-saving benefits of teleconsultation, especially in a post-COVID-19 era. This exploratory retrospective study examined the proportion of post-colonoscopy follow-up consultations that could have been converted to teleconsultation within a tertiary hospital in Singapore. METHODS: A retrospective cohort of all patients who underwent colonoscopy in the institution from July to September 2019 was identified. All follow-up face-to-face consultations related to the index colonoscopy from the scope date to 6 months post-colonoscopy were traced. Clinical data relevant to the index colonoscopy and these consultations were extracted from electronic medical records. RESULTS: The cohort consisted of 859 patients (68.5% male, age range: 18-96 years). Of these, 15 (1.7%) had colorectal cancer, but the majority (n = 643, 74.9%) were scheduled for at least one post-colonoscopy visit - a total of 884 face-to-face clinical visits. The final sample was 682 (77.1%) face-to-face post-colonoscopy visits that did not involve any procedures performed or indicated the need for any subsequent follow-up. CONCLUSION: If such "unnecessary" post-colonoscopy consultations exist within our institution, then similar situations possibly occur elsewhere. As COVID-19 continues to periodically tax healthcare systems worldwide, preservation of resources will remain integral alongside quality standards of routine patient care. There is a need for detailed analyses and modeling to hypothesize potential savings by also considering the start-up and maintenance costs of switching to a teleconsultation-dominated system.


Assuntos
COVID-19 , Neoplasias Colorretais , Consulta Remota , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Seguimentos , COVID-19/epidemiologia , Consulta Remota/métodos , Colonoscopia
19.
PLoS One ; 18(2): e0281557, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36763684

RESUMO

BACKGROUND: Colorectal cancer (CRC) screening using the faecal immunochemical test (FIT) kits based on the detection of occult blood in stool is widely advocated in numerous screening programs worldwide. However, CRC is not commonly diagnosed in positive cases. We undertook this review to determine if there is evidence to suggest the use of opportunistic oesophago-gastro-duodenoscopy (OGD) in patients without CRC. METHODS: A systematic review encompassing three electronic databases was performed. All peer-reviewed studies of FIT-positive patients who underwent either OGD and colonoscopy concurrently or OGD post-colonoscopy were included. Only studies from 2008 to 2022 using FIT kits were included to ensure studies not previously included in an earlier review were being analysed. A forward citation search of the included articles was also conducted to ensure no relevant articles were missed. RESULTS: A total of 2409 records were extracted. Only four studies fulfilled the selection criteria and were included. Although the rates of abnormal OGD results were relatively high in the four studies, only 3 of 605 (0.50%) patients had gastric cancer in the entire review sample. No other malignancies were identified in all four studies. Other notable pathologies such as gastric polyps and gastritis were also reported. CONCLUSIONS: There is little overall evidence to recommend UGI screening for all FIT-positive patients following a colonoscopy. However, there may be a role for clinicians to consider opportunistic OGD in this group of patients. Future research should examine patient populations from other sociocultural contexts including cost-effective analysis when considering changes in health guidelines on UGI screening.


Assuntos
Neoplasias Colorretais , Gastroscopia , Humanos , Sangue Oculto , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Programas de Rastreamento/métodos , Detecção Precoce de Câncer/métodos , Fezes
20.
Frontline Gastroenterol ; 14(1): 87, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36561779
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