Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.008
Filtrar
1.
Surg Oncol Clin N Am ; 32(1): 119-141, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36410912

RESUMO

Despite a steady decline in incidence and mortality rates, colorectal cancer (CRC) remains the second most common cancer diagnosis in women and the third most common in men worldwide. Notably, the liver is recognized as the most common site of CRC metastasis, and metastases to the liver remain the primary driver of disease-specific mortality for patients with CRC. Although hepatic resection is the backbone of curative-intent treatment, management of CRLM has become increasingly multimodal during the last decade and includes the use of downstaging chemotherapy, ablation techniques, and locoregional therapy, each of which are reviewed herein.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Terapia Combinada , Neoplasias Hepáticas/terapia , Neoplasias Colorretais/terapia
2.
Sci Rep ; 12(1): 20075, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36418865

RESUMO

Carcinoembryonic antigen (CEA) levels and imaging are used to guide treatment for metastatic colorectal cancer (mCRC). This study evaluated changes in CEA and imaging findings in mCRC patients following systemic therapy and their clinical significance, especially the ones with inconsistent results of CEA and image findings. We enrolled 330 stage IV CRC patients who systemic therapy. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and a modification for CEA, patients were stratified into consistent and inconsistent response groups. Clinicopathological features and prognoses were compared between each groups. Different CEA/IMG groups showed no significant differences in terms of tumor location, initial CEA level, mucinous component, tumor differentiation and further surgical treatment rate. Inconsistent responses were observed in half of the patients (n = 165, 50%). The prognosis in the inconsistent groups with either CEA-SD or IMG-SD was dependent on the result of the other evaluation method (PR or PD). Cases with conflicting results between CEA and image groups (CEA-RD/IMG-PD, CEA-PD/IMG-PR) had an OS close to that of CEA-SD/IMG-SD (18.2 m, 16.2 m vs. 18.8 m, P = 0.620). The overall survival (OS) in the consistent (PR/PR ro PD/PD) groups were significantly different (P < 0.001). Combining CEA and imaging provides more information about mCRC patients who have undergone systemic therapy. Approximately half the patients have inconsistent responses, which is still valuable in predicting the prognosis.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Antígeno Carcinoembrionário , Prognóstico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Critérios de Avaliação de Resposta em Tumores Sólidos
3.
BMC Med Inform Decis Mak ; 21(Suppl 11): 369, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36419042

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease with different responses to targeted therapies due to various factors, and the treatment effect differs significantly between individuals. Personalize medical treatment (PMT) is a method that takes individual patient characteristics into consideration, making it the most effective way to deal with this issue. Patient similarity and clustering analysis is an important aspect of PMT. This paper describes how to build a knowledge base using formal concept analysis (FCA), which clusters patients based on their similarity and preserves the relations between clusters in hierarchical structural form. METHODS: Prognostic factors (attributes) of 2442 CRC patients, including patient age, cancer cell differentiation, lymphatic invasion and metastasis stages were used to build a formal context in FCA. A concept was defined as a set of patients with their shared attributes. The formal context was formed based on the similarity scores between each concept identified from the dataset, which can be used as a knowledge base. RESULTS: A hierarchical knowledge base was constructed along with the clinical records of the diagnosed CRC patients. For each new patient, a similarity score to each existing concept in the knowledge base can be retrieved with different similarity calculations. The ranked similarity scores that are associated with the concepts can offer references for treatment plans. CONCLUSIONS: Patients that share the same concept indicates the potential similar effect from same clinical procedures or treatments. In conjunction with a clinician's ability to undergo flexible analyses and apply appropriate judgement, the knowledge base allows faster and more effective decisions to be made for patient treatment and care.


Assuntos
Neoplasias Colorretais , Assistência ao Paciente , Humanos , Bases de Conhecimento , Análise por Conglomerados , Julgamento , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia
4.
Front Immunol ; 13: 994828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405728

RESUMO

Introduction: The migrasome is a newly discovered organelle that resembles extracellular vesicles in structure. However, the function of the migrasome in tumors, particularly in relation to tumor immunity and tumor microenvironment, is unclear. Methods: Gene expression data, copy number variation raw data, and methylation data of 33 cancer types were downloaded from The Cancer Genome Atlas database. Immunohistochemistry (IHC) based on 114 case of colorectal cancer was used to validate the expression of the migrasome hub-gene. We analyzed the expression, prognosis, genetic variation, and drug sensitivity profiles of migrasome-related genes (MRGs) in pan-cancer datasets. A migrasome score was constructed based on gene set enrichment analysis, and the correlation of migrasomes with the tumor microenvironment was assessed. The CancerSEA was used to perform a single-cell level functional analysis of the migrasome. Additionally, we also analyzed the correlation between migrasomes and tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion scores. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of migrasomes in the tumor microenvironment. Results: PIGK expression was significantly up-regulated in 22 of 33 tumors, and high expression of migrasome was estimated to have contributed to poor prognosis. Missense mutations are the most common type of mutation in MRGs. We identified piperlongumine as a potential drug targeting migrasomes. The migrasome score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the abundance of macrophages in the tumor microenvironment was significantly and positively correlated with the migrasome score. Additionally, the migrasome scores were significantly correlated with the immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including TMB and MSI. According to scRNA-seq analysis, migrasome differed significantly among cells of the tumor microenvironment. IHC confirmed low expression of ITGA5 and PIGK in colorectal cancer. Discussion: We performed the first pan-cancer analysis of migrasomes and discovered that they play an important role in tumor development and immune escape. Our study provides new insights into the role of migrasomes in tumor prognosis and immunotherapy.


Assuntos
Neoplasias Colorretais , Variações do Número de Cópias de DNA , Humanos , Organelas , Imunoterapia , Instabilidade de Microssatélites , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/metabolismo , Microambiente Tumoral/genética
5.
Front Immunol ; 13: 1029269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405739

RESUMO

Colorectal cancer is the third most diagnosed cancer and the second leading cause of cancer mortality worldwide, highlighting an urgent need for new therapeutic options and combination strategies for patients. The orchestration of potent T cell responses against human cancers is necessary for effective antitumour immunity. However, regression of a limited number of cancers has been induced by immune checkpoint inhibitors, T cell engagers (TCEs) and/or oncolytic viruses. Although one TCE has been FDA-approved for the treatment of hematological malignancies, many challenges exist for the treatment of solid cancers. Here, we show that TCEs targeting CEACAM5 and CD3 stimulate robust activation of CD4 and CD8-positive T cells in in vitro co-culture models with colorectal cancer cells, but in vivo efficacy is hindered by a lack of TCE retention in the tumour microenvironment and short TCE half-life, as demonstrated by HiBiT bioluminescent TCE-tagging technology. To overcome these limitations, we engineered Bispecific Engager Viruses, or BEVirs, a novel tumour-targeted vaccinia virus platform for intra-tumour delivery of these immunomodulatory molecules. We characterized virus-mediated TCE-secretion, TCE specificity and functionality from infected colorectal cancer cells and patient tumour samples, as well as TCE cytotoxicity in spheroid models, in the presence and absence of T cells. Importantly, we show regression of colorectal tumours in both syngeneic and xenograft mouse models. Our data suggest that a different profile of cytokines may contribute to the pro-inflammatory and immune effects driven by T cells in the tumour microenvironment to provide long-lasting immunity and abscopal effects. We establish combination regimens with immune checkpoint inhibitors for aggressive colorectal peritoneal metastases. We also observe a significant reduction in lung metastases of colorectal tumours through intravenous delivery of our oncolytic virus driven T-cell based combination immunotherapy to target colorectal tumours and FAP-positive stromal cells or CTLA4-positive Treg cells in the tumour microenvironment. In summary, we devised a novel combination strategy for the treatment of colorectal cancers using oncolytic vaccinia virus to enhance immune-payload delivery and boost T cell responses within tumours.


Assuntos
Neoplasias Colorretais , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Camundongos , Animais , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Vírus Vaccinia , Modelos Animais de Doenças , Neoplasias Colorretais/terapia , Microambiente Tumoral
7.
Front Immunol ; 13: 1014834, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389750

RESUMO

Background: Transient receptor potential channels (TRPC) play critical regulatory functions in cancer occurrence and progression. However, knowledge on its role in colorectal cancer (CRC) is limited. In addition, neoadjuvant treatment and immune checkpoint inhibitors (ICIs) have increasing roles in CRC management, but not all patients benefit from them. In this study, a TRPC related signature (TRPCRS) was constructed for prognosis, tumor immune microenvironment (TIME), and treatment response of CRC. Methods: Data on CRC gene expression and clinical features were retrospectively collected from TCGA and GEO databases. Twenty-eight TRPC regulators (TRPCR) were retrieved using gene set enrichment analysis. Different TRPCR expression patterns were identified using non-negative matrix factorization for consensus clustering, and a TRPCRS was established using LASSO. The potential value of TRPCRS was assessed using functional enrichment analysis, tumor immune analysis, tumor somatic mutation analysis, and response to preoperative chemoradiotherapy or ICIs. Moreover, an external validation was conducted using rectal cancer samples that received preoperative chemoradiotherapy at Fujian Cancer Hospital (FJCH) via qRT-PCR. Results: Among 834 CRC samples in the TCGA and meta-GEO cohorts, two TRPCR expression patterns were identified, which were associated with various immune infiltrations. In addition, 266 intersected genes from 5564 differentially expressed genes (DEGs) between two TRPC subtypes, 4605 DEGs between tumor tissue and adjacent non-tumor tissue (all FDR< 0.05, adjusted P< 0.001), and 1329 prognostic related genes (P< 0.05) were identified to establish the TRPCRS, which was confirmed in the TCGA cohort, two cohorts from GEO, and one qRT-PCR cohort from FJCH. According to the current signature, the high-TRPC score group had higher expressions of PD-1, PD-L1, and CTLA4, lower TIDE score, and improved response to anti-PD-1 treatment with better predictive ability. Compared to the high-TRPC score group, the low-TRPC score group comprised an immunosuppressive phenotype with increased infiltration of neutrophils and activated MAPK signaling pathway, but was more sensitive to preoperative chemoradiotherapy and associated with improved prognosis. Conclusions: The current TRPCRS predicted the prognosis of CRC, evaluated the TIME in CRC, and anticipated the response to immune therapy and neoadjuvant treatment.


Assuntos
Neoplasias Colorretais , Canais de Potencial de Receptor Transitório , Humanos , Canais de Potencial de Receptor Transitório/metabolismo , Estudos Retrospectivos , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Prognóstico , Microambiente Tumoral/genética
8.
Front Immunol ; 13: 984480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389763

RESUMO

The incidence and mortality of colorectal cancer (CRC) are increasing year by year. The accurate classification of CRC can realize the purpose of personalized and precise treatment for patients. The tumor microenvironment (TME) plays an important role in the malignant progression and immunotherapy of CRC. An in-depth understanding of the clusters based on the TME is of great significance for the discovery of new therapeutic targets for CRC. We extracted data on CRC, including gene expression profile, DNA methylation array, somatic mutations, clinicopathological information, and copy number variation (CNV), from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) (four datasets-GSE14333, GSE17538, GSE38832, and GSE39582), cBioPortal, and FireBrowse. The MCPcounter was utilized to quantify the abundance of 10 TME cells for CRC samples. Cluster repetitive analysis was based on the Hcluster function of the Pheatmap package in R. The ESTIMATE package was applied to compute immune and stromal scores for CRC patients. PCA analysis was used to remove batch effects among different datasets and transform genome-wide DNA methylation profiling into methylation of tumor-infiltrating lymphocyte (MeTIL). We evaluated the mutation differences of the clusters using MOVICS, DeconstructSigs, and GISTIC packages. As for therapy, TIDE and SubMap analyses were carried out to forecast the immunotherapy response of the clusters, and chemotherapeutic sensibility was estimated based on the pRRophetic package. All results were verified in the TCGA and GEO data. Four immune clusters (ImmClust-CS1, ImmClust-CS2, ImmClust-CS3, and ImmClust-CS4) were identified for CRC. The four ImmClusts exhibited distinct TME compositions, cancer-associated fibroblasts (CAFs), functional orientation, and immune checkpoints. The highest immune, stromal, and MeTIL scores were observed in CS2, in contrast to the lowest scores in CS4. CS1 may respond to immunotherapy, while CS2 may respond to immunotherapy after anti-CAFs. Among the four ImmClusts, the top 15 markers with the highest mutation frequency were acquired, and CS1 had significantly lower CNA on the focal level than other subtypes. In addition, CS1 and CS2 patients had more stable chromosomes than CS3 and CS4. The most sensitive chemotherapeutic agents in these four ImmClusts were also found. IHC results revealed that CD29 stained significantly darker in the cancer samples, indicating that their CD29 was highly expressed in colon cancer. This work revealed the novel clusters based on TME for CRC, which would guide in predicting the prognosis, biological features, and appropriate treatment for patients with CRC.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Variações do Número de Cópias de DNA , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Prognóstico , Imunoterapia
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 25(11): 1012-1019, 2022 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-36396377

RESUMO

Objective: To compare the effects of three treatment options: emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery, on the pathological characteris- tics of surgically-resected specimens from patients with completely obstructive colorectal cancer. Methods: This was a retrospective cohort study analyzing clinicopathological data of patients with complete obstructive colorectal cancer who were admitted to the General Surgery Department of Beijing Chaoyang Hospital, Capital Medical University, between May 2012 and August 2020. The inclusion criteria were diagnosed with complete colorectal obstruction, pathologically confirmed as adenocarcinoma, resectable on imaging assessment, and without distant metastasis, combined with the patients' clinical manifestations and imaging examination findings. Patients with multiple colorectal cancers, refusal to undergo surgery, and concurrent peritonitis or intestinal perforation before stenting of the intestinal obstruction were excluded. Eighty-nine patients with completely obstructive colorectal cancer were enrolled in the study and were divided into emergency surgery group (n=30), stent-surgery group (n=34), and stent-neoadjuvant chemotherapy- surgery group (n=25) according to the treatment strategy. Differences in the pathological features (namely perineural infiltration, lymphovascular infiltration, tumor deposits, specimen intravascular necrosis, inflammatory infiltration, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cell ratio) and biomolecular markers (namely cluster of differentiation (CD)34, Ki67, Bcl-2, matrix metalloproteinase-9, and hypoxia-inducible factor alpha) were recorded. Pathological evaluation was based on the presence or absence of qualitative evaluation of pathological features, such as peripheral nerve infiltration, vascular infiltration, and cancer nodules within the specimens. The evaluation criteria for the pathological features of the specimens were as follows: Semi-quantitative graded evaluation based on the proportion of tissue necrosis, inflammatory infiltrates, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cells in the field of view within the specimen were classified as: grade 0: not seen within the specimen; grade 1: 0-25%; grade 2: 25%-50%; grade 3: 50%-75%; and grade 4: 75%-100%. The intensity of cellular immunity was classified as none (0 points), weak (1 point), moderate (2 points), and strong (3 points). The two evaluation scores were then multiplied to obtain a total score of 0-12. The immunohistochemical results were also evaluated comprehensively, and the results were defined as: negative (grade 0): 0 points; weakly positive (grade 1): 1-3 points; moderately positive (grade 2): 4-6 points; strongly positive (grade 3): 7-9 points; and very strong positive (grade 4): 10-12 points. Normally-distributed values were expressed as mean±standard deviation, and one-way analysis of variance was used to analyze the differences between the groups. Non-normally-distributed values were expressed as median (interquartile range: Q1, Q3). A nonparametric test (Kruskal-Wallis H test) was used for comparisons between groups. Results: The differences were not statistically significant when comparing the baseline data for age, gender, tumor site, American Society of Anesthesiologists score, tumor T-stage, N-stage, and degree of differentiation among the three groups (all P>0.05). The differences were not statistically significant when comparing the pathological characteristics of the resected tumor specimens, such as foreign body giant cells, inflammatory infiltration, and mucus lake formation among the three groups (all P>0.05). The rates of vascular infiltration were 56.6% (17/30), 41.2% (15/34), and 20.0% (5/25) in the emergency surgery, stent-surgery, and stent- neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences between the groups (χ2=7.142, P=0.028). Additionally, the rate of vascular infiltration was significantly lower in the stent-neoadjuvant chemotherapy-surgery group than that in the emergency surgery group (P=0.038). Peripheral nerve infiltration rates were 55.3% (16/30), 41.2% (14/34), and 16.0% (4/25), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (χ2=7.735, P=0.021). The infiltration peripheral nerve rates in the stent-neoadjuvant chemotherapy-surgery group were significantly lower than those in the emergency surgery group (P=0.032). The necrosis grade was 2 (1, 2), 2 (1, 3), and 2 (2, 3) in the emergency surgery, stent- surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=10.090, P=0.006). Post hoc comparison revealed that the necrosis grade was higher in the stent-surgery and stent-neoadjuvant chemotherapy-surgery groups compared with the emergency surgery group (both P<0.05). The abscess grade was 2 (1, 2), 3 (1, 3), and 2 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=6.584, P=0.037). Post hoc comparison revealed that the abscess grade in the emergency surgery group was significantly lower than that in the stent-surgery group (P=0.037). The fibrosis grade was 2 (1, 3), 3 (2, 3), and 3 (2, 3), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=11.078, P=0.004). Post hoc analysis revealed that the fibrosis degree was higher in both the stent-surgery group and the stent- neoadjuvant chemotherapy-surgery group compared with the emergency surgery group (both, P<0.05). The tumor cell ratio grades were 4 (3, 4), 4 (3, 4), and 3 (2, 4), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=8.594, P=0.014). Post hoc analysis showed that the tumor cell ratio in the stent-neoadjuvant chemotherapy-surgery group was significantly lower than that in the emergency surgery group (P=0.012). The CD34 grades were 2 (2, 3), 3 (2, 4), and 3 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, and the difference was statistically significant (H=9.786, P=0.007). Post hoc analysis showed that the CD34 grades in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups were 2 (2, 3), 3 (2, 4), and 3 (2,3), respectively. Post hoc analysis revealed that the CD34 concentration was higher in the stent-surgery group than that in the emergency surgery group (P=0.005). Conclusion: Stenting may increase the risk of distant metastases in obstructive colorectal cancer. The stent-neoadjuvant chemotherapy-surgery treatment model promotes tumor cell necrosis and fibrosis and reduces the proportion of tumor cells, vascular infiltration, and peripheral nerve infiltration, which may help decrease local tumor infiltration and distant metastasis in completely obstructive colorectal cancer after stent placement.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Humanos , Terapia Neoadjuvante/métodos , Abscesso , Estudos Retrospectivos , Obstrução Intestinal/etiologia , Stents , Neoplasias Colorretais/complicações , Neoplasias Colorretais/terapia , Necrose
10.
Nature ; 611(7936): 603-613, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36352230

RESUMO

Around 30-40% of patients with colorectal cancer (CRC) undergoing curative resection of the primary tumour will develop metastases in the subsequent years1. Therapies to prevent disease relapse remain an unmet medical need. Here we uncover the identity and features of the residual tumour cells responsible for CRC relapse. An analysis of single-cell transcriptomes of samples from patients with CRC revealed that the majority of genes associated with a poor prognosis are expressed by a unique tumour cell population that we named high-relapse cells (HRCs). We established a human-like mouse model of microsatellite-stable CRC that undergoes metastatic relapse after surgical resection of the primary tumour. Residual HRCs occult in mouse livers after primary CRC surgery gave rise to multiple cell types over time, including LGR5+ stem-like tumour cells2-4, and caused overt metastatic disease. Using Emp1 (encoding epithelial membrane protein 1) as a marker gene for HRCs, we tracked and selectively eliminated this cell population. Genetic ablation of EMP1high cells prevented metastatic recurrence and mice remained disease-free after surgery. We also found that HRC-rich micrometastases were infiltrated with T cells, yet became progressively immune-excluded during outgrowth. Treatment with neoadjuvant immunotherapy eliminated residual metastatic cells and prevented mice from relapsing after surgery. Together, our findings reveal the cell-state dynamics of residual disease in CRC and anticipate that therapies targeting HRCs may help to avoid metastatic relapse.


Assuntos
Neoplasias Colorretais , Metástase Neoplásica , Proteínas de Neoplasias , Recidiva Local de Neoplasia , Neoplasia Residual , Receptores de Superfície Celular , Animais , Humanos , Camundongos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Progressão da Doença , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/genética , Neoplasia Residual/patologia , Receptores de Superfície Celular/deficiência , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Metástase Neoplásica/terapia , Modelos Animais de Doenças , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante , Imunoterapia
11.
Curr Oncol ; 29(11): 8609-8625, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36421332

RESUMO

Outcome disparities between adults <50 with colorectal cancer (CRC) and older adults may be explained by clinical delays. This study synthesized the literature comparing delays and outcomes between younger and older adults with CRC. Databases were searched until December 2021. We included studies published after 1990 reporting delay in adults <50 that made comparisons to older adults. Comparisons were described narratively and stage between age groups was meta-analyzed. 39 studies were included representing 185,710 younger CRC patients and 1,422,062 older patients. Sixteen delay intervals were compared. Fourteen studies (36%) found significantly longer delays among younger adults, and nine (23%) found shorter delays among younger patients. Twelve studies compared time from symptom onset to diagnosis (N younger = 1538). Five showed significantly longer delays for younger adults. Adults <50 years also had higher odds of advanced stage (16 studies, pooled OR for Stage III/IV 1.76, 95% CI 1.52-2.03). Ten studies compared time from diagnosis to treatment (N younger = 171,726) with 4 showing significantly shorter delays for younger adults. All studies showing longer delays for younger adults examined pre-diagnostic intervals. Three studies compared the impact of delay on younger versus older adult. One showed longer delays were associated with advanced stage and worse survival in younger but not older adults. Longer delays among younger adults with CRC occur in pre-diagnostic intervals.


Assuntos
Neoplasias Colorretais , Humanos , Idoso , Bases de Dados Factuais , Neoplasias Colorretais/terapia , Neoplasias Colorretais/diagnóstico
12.
Curr Oncol ; 29(11): 8751-8766, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36421342

RESUMO

Research suggests that colorectal cancer (CRC) is associated with mental health disorders, primarily anxiety and depression. To synthesize this evidence, we conducted a systematic review and meta-analysis of studies evaluating the onset of anxiety and depression among patients with CRC. We searched EMBASE and Medline from inception to June 2022. We included original, peer-reviewed studies that: used an epidemiologic design; included patients with CRC and a comparator group of individuals without cancer; and evaluated anxiety and depression as outcomes. We used random effects models to obtain pooled measures of associations. Quality assessment was completed using the Newcastle-Ottawa scale. Of 7326 articles identified, 8 were eligible; of which 6 assessed anxiety and depression and 2 assessed depression only. Meta-analyses showed a non-significant association between CRC and anxiety (pooled HR 1.67; 95% CI 0.88 to 3.17) and a significant association between CRC and depression (pooled HR 1.78; 95% CI 1.23 to 2.57). Predictors of anxiety and depression among patients with CRC included clinical characteristics (e.g., comorbidities, cancer stage, cancer site), cancer treatment (e.g., radiotherapy, chemotherapy, colostomy), and sociodemographic characteristics (e.g., age, sex). The impacts of anxiety and depression in patients with CRC included increased mortality and decreased quality of life. Altogether, our systematic review and meta-analysis quantified the risks and impacts of CRC on anxiety and depression, particularly an increased risk of depression after CRC diagnosis. Findings provide support for oncologic care that encompasses mental health supports for patients with CRC.


Assuntos
Neoplasias Colorretais , Depressão , Humanos , Depressão/epidemiologia , Depressão/etiologia , Qualidade de Vida , Ansiedade/epidemiologia , Ansiedade/etiologia , Comorbidade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia
13.
Epidemiol Psychiatr Sci ; 31: e82, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36384819

RESUMO

AIMS: People with severe mental illness (SMI) have a greater risk of dying from colorectal cancer (CRC), even though the incidence is lower or similar to that of the general population This pattern is unlikely to be solely explained by lifestyle factors, while the role of differences in cancer healthcare access or treatment is uncertain. METHODS: We undertook a systematic review and meta-analysis on access to guideline-appropriate care following CRC diagnosis in people with SMI including the receipt of surgery, chemo- or radiotherapy. We searched for full-text articles indexed by PubMed, EMBASE, PsychInfo and CINAHL that compared CRC treatment in those with and without pre-existing SMI (schizophrenia, schizoaffective, bipolar and major affective disorders). Designs included cohort or population-based case-control designs. RESULTS: There were ten studies (sample size = 3501-591 561). People with SMI had a reduced likelihood of surgery (RR = 0.90, 95% CI 0.92-0.97; p = 0.005; k = 4). Meta-analyses were not possible for the other outcomes but in results from individual studies, people with SMI were less likely to receive radiotherapy, chemotherapy or sphincter-sparing procedures. The disparity in care was greatest for those who had been psychiatric inpatients. CONCLUSIONS: People with SMI, including both psychotic and affective disorders, receive less CRC care than the general population. This might contribute to higher case-fatality rates for an illness where the incidence is no higher than that of the general population. The reasons for this require further investigation, as does the extent to which differences in treatment access or quality contribute to excess CRC mortality in people with SMI.


Assuntos
Neoplasias Colorretais , Transtornos Mentais , Esquizofrenia , Humanos , Canal Anal , Tratamentos com Preservação do Órgão , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/terapia
14.
Sci Rep ; 12(1): 20442, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443338

RESUMO

An enriched environment (EE) is a promising strategy for protecting the intestinal mucosal barrier and regulating the brain-gut axis, but the optimal EE intervention duration is unknown. Here, different EE intervention durations were applied to assess the optimal intervention duration in rats with colorectal cancer. We used a rat model of 1, 2-dimethylhydrazine-induced colorectal cancer. The rats were housed in an EE for 0, 2, 4, 8 weeks and 8-week blank group. The intestinal mucosa and serum TNF-α, IL-6, IL-10, ATP, CRF, and occludin levels and bacterial translocation (BT) were measured, and the intestinal mucosa morphology was evaluated. In 8 weeks, the effect of tumor on intestinal mucosal barrier was not obvious and the EE had a greater impact on it. Eight weeks of EE was more beneficial to the intestinal mucosal mechanical barrier than 2 or 4 weeks of intervention. A significant difference in BT was found between the 4- and 8-week groups. Overall, the analysis of inflammatory factor regulation revealed that the two blank groups exhibited the worst effect, and the intervention effect at 8 weeks was better than that at 2 and 4 weeks. CRF at 4 weeks was higher than that at 8-week blank group. The effect of 8-week intervention duration on the intestinal mucosal barrier was generally better than that of 2- and 4-week durations and intervention within 4 weeks can help to stabilize and promote the secretion of brain gut peptide, but the effect of different intervention durations on the brain-gut peptide levels was not obvious. In the future, we can further explore the molecular biological mechanism of the effect of different EE intervention durations on the intestinal mucosal barrier and analyze the effect of an EE on other brain-gut peptides.


Assuntos
Eixo Encéfalo-Intestino , Neoplasias Colorretais , Animais , Ratos , Translocação Bacteriana , Mucosa Intestinal , Ocludina , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/terapia
15.
Front Immunol ; 13: 1030745, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36426359

RESUMO

Accumulating evidence suggests that gut microbial dysbiosis is implicated in colorectal cancer (CRC) initiation and progression through interaction with host immune system. Given the intimate relationship between the gut microbiota and the antitumor immune responses, the microbiota has proven to be effective targets in modulating immunotherapy responses of preclinical CRC models. However, the proposed putative mechanisms of how these bacteria affect immune responses and immunotherapy efficacy remains obscure. In this review, we summarize recent findings of clinical gut microbial dysbiosis in CRC patients, the reciprocal interactions between gut microbiota and the innate and/or the adaptive immune system, as well as the effect of gut microbiota on immunotherapy response in CRC. Increased understanding of the gut microbiota-immune system interactions will benefit the rational application of microbiota to the clinical promising biomarker or therapeutic strategy as a cancer immunotherapy adjuvant.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Disbiose/microbiologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/microbiologia , Imunidade , Imunoterapia
16.
PLoS One ; 17(10): e0273692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36206231

RESUMO

INTRODUCTION: Nowadays, the burden of colorectal cancer (CRC) has been increasing in the world, particularly in developing nations. This could be related to the poor prognosis of the disease due to late presentation at diagnosis and poor treatment outcomes. In Ethiopia, studies related to the stage of colorectal cancer at diagnosis and its determinants are limited. Therefore, the study was intended to assess advanced stage presentation and its associated factors among colorectal cancer patients in northwest Ethiopia. METHODS: An institution-based retrospective study was conducted among 367 CRC patients at two oncologic centers (the University of Gondar and Felege Hiwot comprehensive specialized hospitals) from January 1, 2017, to December 31, 2020. Data were entered into EPi-data 4.2.0.0 and transferred to STATA version 14 statistical software for analysis. Binary logistic regression was used to identify factors associated with the outcome variable. All variables with P-value < 0.2 during bi-variable analysis were considered for multivariable logistic regression. The level of statistical significance was declared at P-value <0.05. RESULTS: The magnitude of advanced stage presentation of colorectal cancer was 83.1%. Being rural dwellers (Adjusted odds ratio (AOR) = 3.6; 95% CI: 1.8,7.2), not medically insured (AOR = 3.9; 95% CI: 1.9,7.8), patients delay (AOR = 6.5; 95% CI:3.2, 13.3), recurrence of the disease (AOR = 2.3; 95% CI: 1.1,4.7), and no comorbidity illness (AOR = 4.4; 95% CI: 2.1, 9.1) were predictors of advanced stage presentation of CRC. CONCLUSION: The current study revealed that the advanced-stage presentation of colorectal cancer patients was high. It is recommended that the community shall be aware of the signs and symptoms of the disease using different media, giving more emphasis to the rural community, expanding health insurance, and educating patients about the recurrence chance of the disease. Moreover, expansion of colorectal treatment centers and screening of colorectal cancer should be given emphasis.


Assuntos
Neoplasias Colorretais , Encaminhamento e Consulta , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Etiópia/epidemiologia , Hospitais , Humanos , Estudos Retrospectivos
17.
Vnitr Lek ; 68(2): 116-122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36208926

RESUMO

Diabetes mellitus (type 2 diabetes in particular) and colorectal carcinoma are relatively frequent diseases in our population. At the same time, these units share some common risk factors, for example obesity, lack of physical activity and hyperinsulinemia. Available data show patients with diabetes have increased risk of colorectal adenoma and carcinoma, increased risk of colorectal carcinoma at a lower age, as well as increased risk of relapse and increased mortality with colorectal cancer. The aim of this article is to point out the relationship between diabetes and colorectal carcinoma, with emphasis on the information important for clinical practice, particularly the screening of colorectal carcinoma and lifestyle recommendations for patients with diabetes. Therefore, we offer an overview of the important available publications which consider this topic.


Assuntos
Adenoma , Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Adenoma/diagnóstico , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Recidiva Local de Neoplasia , Fatores de Risco
18.
Front Immunol ; 13: 951455, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189298

RESUMO

Background: Colorectal cancer (CRC) is one of the most common digestive system tumors worldwide. Hypoxia and immunity are closely related in CRC; however, the role of hypoxia-immune-related lncRNAs in CRC prognosis is unknown. Methods: Data used in the current study were sourced from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases. CRC patients were divided into low- and high-hypoxia groups using the single-sample gene set enrichment analysis (ssGSEA) algorithm and into low- and high-immune groups using the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm. Differentially expressed lncRNAs (DElncRNAs) between low- and high-hypoxia groups, low- and high-immune groups, and tumor and control samples were identified using the limma package. Hypoxia-immune-related lncRNAs were obtained by intersecting these DElncRNAs. A hypoxia-immune-related lncRNA risk signature was developed using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses. The tumor microenvironments in the low- and high-risk groups were evaluated using ssGSEA, ESTIMATE, and the expression of immune checkpoints. The therapeutic response in the two groups was assessed using TIDE, IPS, and IC50. A ceRNA network based on signature lncRNAs was constructed. Finally, we used RT-qPCR to verify the expression of hypoxia-immune-related lncRNA signatures in normal and cancer tissues. Results: Using differential expression analysis, and univariate Cox and LASSO regression analyses, ZNF667-AS1, LINC01354, LINC00996, DANCR, CECR7, and LINC01116 were selected to construct a hypoxia-immune-related lncRNA signature. The performance of the risk signature in predicting CRC prognosis was validated in internal and external datasets, as evidenced by receiver operating characteristic curves. In addition, we observed significant differences in the tumor microenvironment and immunotherapy response between low- and high-risk groups and constructed a CECR7-miRNA-mRNA regulatory network in CRC. Furthermore, RT-qPCR results confirmed that the expression patterns of the six lncRNA signatures were consistent with those in TCGA-CRC cohort. Conclusion: Our study identified six hypoxia-immune-related lncRNAs for predicting CRC survival and sensitivity to immunotherapy. These findings may enrich our understanding of CRC and help improve CRC treatment. However, large-scale long-term follow-up studies are required for verification.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/genética , Imunoterapia , Estimativa de Kaplan-Meier , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Microambiente Tumoral/genética
19.
Front Immunol ; 13: 1016646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238278

RESUMO

Colorectal cancer (CRC) is the third most common cancer in the world. Although there are standard treatment options for CRC, most patients respond poorly to these treatments. Immunotherapies have gradually emerged due to the increasing awareness and understanding of tumor immunity, exhibiting good therapeutic efficacy in various cancers. Immunotherapies include cytokines, immune checkpoint inhibitors (ICIs), and adoptive cell therapies. In particular, ICIs, which are antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), or its ligand PD-L1, have been successfully applied clinically for solid tumors, relieving the inhibitory effect of the tumor microenvironment on T cells. However, only a minority of patients with cancer achieve a durable clinical response during immunotherapy. Several factors restrict the efficacy of immunotherapy, leading to the development of drug resistance. In this review, we aimed to discuss the current status of immunotherapy for CRC and elaborate on the mechanisms that mediate resistance to immunotherapy and other potential therapeutic strategies.


Assuntos
Antígeno B7-H1 , Neoplasias Colorretais , Antígeno CTLA-4 , Neoplasias Colorretais/terapia , Citocinas , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos , Imunoterapia , Ligantes , Receptor de Morte Celular Programada 1 , Microambiente Tumoral
20.
Front Immunol ; 13: 904137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238297

RESUMO

Colorectal cancer (CRC) is the third most common cancer, with a high mortality rate and a serious impact on people's life and health. In recent years, adoptive chimeric antigen receptor T (CAR-T) cells therapy has shown well efficacy in the treatment of hematological malignancies, but there are still many problems and challenges in solid tumors such as CRC. For example, the tumor immunosuppressive microenvironment, the low targeting of CAR-T cells, the short time of CAR-T cells in vivo, and the limited proliferation capacity of CAR-T cells, CAR-T cells can not effectively infiltrate into the tumor and so on. New approaches have been proposed to address these challenges in CRC, and this review provides a comprehensive overview of the current state of CAR-T cells therapy in CRC.


Assuntos
Neoplasias Colorretais , Receptores de Antígenos Quiméricos , Neoplasias Colorretais/terapia , Humanos , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Linfócitos T , Microambiente Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...