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Gestational diabetes mellitus (GDM) is defined as "diagnosed as impaired glucose tolerance for the first time during pregnancy," which can lead to adverse pregnancy outcomes and produces divergent effects on mothers and newborns. In recent years, with the continuous expansion of obese people, GDM shows an upward trend. The abundant and diverse members of the human gut microbiota exert critical roles in the maintenance of human health. Studies have shown that GDM may be associated with disordered gut microbiota in both mothers and newborns. Taking into account the potential effects on maternal and consequently neonatal health, in this review, we analyzed the available data and discussed the current knowledge about the potential relationship between GDM and intestinal dysbiosis in mothers and newborns. In addition, we also discussed the influencing factors derived from GDM mothers on the gut microbiome of their newborns, including the vertical transmission of microbiota from mothers, the alteration of milk components of GDM mothers, and using of probiotics. Hoping that new insights into the role of the gut microbiota in GDM could lead to the development of integrated strategies to prevent and treat these metabolic disorders.
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Background: Sarcoma is a rare and aggressive malignancy with poor prognosis, in which oncogene activation and tumor suppressor inactivation are involved. Accumulated studies suggested basic leucine zipper transcription factor ATF-like 2 (BATF2) as a candidate tumor suppressor, but its specific role and mechanism in sarcoma remain unclear. Methods: The expression levels of BATF2 and miR-939-3p were evaluated by using human sarcoma samples, cell lines and xenograft mouse models. Bioinformatics analysis, qPCR, Western blot, cell proliferation assay, overexpression plasmid construction, point mutation and dual luciferase reporter assay were utilized to investigate the role and mechanism of miR-939-3p in sarcoma. Results: In this study, we demonstrated that the expression of BATF2 was downregulated in human sarcoma tissues and cell lines. The downregulation of BATF2 was negatively associated with the prognosis of sarcoma patients. Subsequent bioinformatic prediction and experimental validations showed that BATF2 expression was reduced by microRNA (miR)-939-3p mimic and increased by miR-939-3p inhibitor. Additionally, miR-939-3p was upregulated in sarcoma tissues and cells, correlating with a poor prognosis of sarcoma patients. Moreover, miR-939-3p overexpression suppressed sarcoma cell proliferation, which was significantly attenuated by the restoration of BATF2, while siRNA-mediated knockdown of BATF2 aggravated the miR-939-3p-induced promotion of sarcoma cell proliferation. Further computational algorithms and dual-luciferase reporter assays demonstrated that miR-939-3p repressed BATF2 expression via directly binding to its 3' untranslated region (3' UTR). Conclusion: Collectively, these findings identified miR-939-3p as a novel regulator of BATF2, as well as a prognostic biomarker in sarcoma, and revealed that suppressing miR-939-3p or inducing BATF2 expression may serve as a promising therapeutic strategy against sarcoma.
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Quantum dots (QDs) represent a class of nanoscale wide bandgap semiconductors, and are primarily composed of metals, lipids, or polymers. Their unique electronic and optical properties, which stem from their wide bandgap characteristics, offer significant advantages for early cancer detection and treatment. Metal QDs have already demonstrated therapeutic potential in early tumor imaging and therapy. However, biological toxicity has led to the development of various non-functionalized QDs, such as carbon QDs (CQDs), graphene QDs (GQDs), black phosphorus QDs (BPQDs) and perovskite quantum dots (PQDs). To meet the diverse needs of clinical cancer treatment, functionalized QDs with an array of modifications (lipid, protein, organic, and inorganic) have been further developed. These advancements combine the unique material properties of QDs with the targeted capabilities of biological therapy to effectively kill tumors through photodynamic therapy, chemotherapy, immunotherapy, and other means. In addition to tumor-specific therapy, the fluorescence quantum yield of QDs has gradually increased with technological progress, enabling their significant application in both in vivo and in vitro imaging. This review delves into the role of QDs in the development and improvement of clinical cancer treatments, emphasizing their wide bandgap semiconductor properties.
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Semiconductor nanomaterials have emerged as a significant factor in the advancement of tumor immunotherapy. This review discusses the potential of transition metal oxide (TMO) nanomaterials in the realm of anti-tumor immune modulation. These binary inorganic semiconductor compounds possess high electron mobility, extended ductility, and strong stability. Apart from being primary thermistor materials, they also serve as potent agents in enhancing the anti-tumor immunity cycle. The diverse metal oxidation states of TMOs result in a range of electronic properties, from metallicity to wide-bandgap insulating behavior. Notably, titanium oxide, manganese oxide, iron oxide, zinc oxide, and copper oxide have garnered interest due to their presence in tumor tissues and potential therapeutic implications. These nanoparticles (NPs) kickstart the tumor immunity cycle by inducing immunogenic cell death (ICD), prompting the release of ICD and tumor-associated antigens (TAAs) and working in conjunction with various therapies to trigger dendritic cell (DC) maturation, T cell response, and infiltration. Furthermore, they can alter the tumor microenvironment (TME) by reprogramming immunosuppressive tumor-associated macrophages into an inflammatory state, thereby impeding tumor growth. This review aims to bring attention to the research community regarding the diversity and significance of TMOs in the tumor immunity cycle, while also underscoring the potential and challenges associated with using TMOs in tumor immunotherapy.
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Colorectal cancer (CRC) from different regions exhibits different histological, genetic characteristics, and molecular subtypes, even in response to conventional chemotherapies and immunotherapies. To characterize the immune landscape in different regions of CRC and search for potential therapeutic targets, we analyzed 39,484 single-cell transcription data from 19 samples of CRC and paired normal tissues from four regions to identify the immune characteristics of CRC among anatomic locations, especially in B cells. We discovered that immune cell infiltration in tumors significantly varied among different regions of CRC. B cells from right- and left-sided CRC had different development trajectories, but both had extensive interactions with myeloid cells and T cells. Survival analysis suggested that CD20+ B cells correlated with good prognosis in CRC patients, especially on the right side. Furthermore, the depletion of CD20+ B cells demonstrated that anti-CD20 promoted tumor growth progression and reversed the tumor-killing activity of anti-PD-1 treatment in vivo and in vitro. Our results highlight the characterization of the immune landscape of CRC in different regions. CD20+ B-cell infiltration has been associated with CRC patient prognosis and may promote the tumor-killing role of PD-1 antibodies.
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Neoplasias Colorrectales , Análisis de Expresión Génica de una Sola Célula , Humanos , Anticuerpos , Linfocitos B , Inmunoterapia , Neoplasias Colorrectales/genética , Pronóstico , Microambiente TumoralRESUMEN
Background: Surgical excision is considered one of the most effective treatments for secondary osteosarcoma (SO). It remains unclear whether the survival of patients with secondary osteosarcoma (SO) could be associated with their surgical willingness. Materials and methods: The statistics of the patients diagnosed with SO between 1975 and 2008 were gathered from the surveillance epidemiology and end results (SEER) database. The patients were divided into three subgroups according to their surgical compliance. The authors used the multivariable Logistic regression analysis and cox regression method to reveal the influence of surgical compliance on prognosis and the risk factors of surgical compliance. Additionally, the authors formulated a nomogram model to predict the overall survival (OS) of patients. The concordance index (C-index) was used to evaluate the accuracy and practicability of the above prediction model. Results: Sixty-three (9.2%) of the 688 patients with SO who were recommended for surgical treatment refused to undergo surgery. Lower surgical compliance can be ascribed to an earlier time of diagnosis and refusal of chemotherapy. The lower overall survival (OS) {[hazard ratio (HR)] 1.733, [CI] 1.205-2.494, P value [P]=0.003} of not surgical compliant patients was verified by the multivariate cox regression method, compared with surgical compliant patients. In addition, the discernibility of the nomogram model was proven to be relatively high (C-index=0.748), by which we can calibrate 3-year- and 5-year OS prediction plots to obtain good concordance to the actual situation. Conclusions: Surgical compliance was proved to be an independent prognostic factor in the survival of patients with SO.
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Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.
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Microbioma Gastrointestinal , Ácido N-Acetilneuramínico , Femenino , Lactante , Embarazo , Humanos , Animales , Ratas , Lactancia , Estudios de Cohortes , Fosfatidilinositol 3-Quinasas , Leche Humana , InmunidadRESUMEN
Recent studies have elucidated the role of lysine-specific demethylase 1 (LSD1), a member of the histone demethylases, in epigenetic regulation of tumor suppressing/promoting genes and neoplastic growth. However, the expression of LSD1 in patients with esophageal squamous cell carcinoma (ESCC) is still unknown. Here, we reported that LSD1 expression was elevated in cancerous tissue and correlated with lymph node metastasis and poorer overall survival in patients with ESCC. Compared to EC109 cells, LSD1 expression was unregulated in aggressive cancer cell lines KYSE450 and KYSE150. Knockdown of LSD1 using lentivirus delivery of LSD1-specific shRNA abrogated the migration and invasion of ESCC cells in vitro. Further, a LSD1 inhibitor, tranylcypromine, suppressed H3K4me2 demethylation and attenuated cellular motility and invasiveness in a dose-dependent manner. Taken together, these data suggested that LSD1 was a potential prognostic maker and may be a molecular target for inhibiting invasion and metastasis in ESCC.
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Carcinoma de Células Escamosas/enzimología , Neoplasias Esofágicas/enzimología , Histona Demetilasas/metabolismo , Secuencia de Bases , Carcinoma de Células Escamosas/patología , Cartilla de ADN , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The human gastrointestinal mucosa is colonized by thousands of microorganisms, which participate in a variety of physiological functions. Intestinal dysbiosis is closely associated with the pathogenesis of several human diseases. Innate lymphoid cells (ILCs), which include NK cells, ILC1s, ILC2s, ILC3s and LTi cells, are a type of innate immune cells. They are enriched in the mucosal tissues of the body, and have recently received extensive attention. The gut microbiota and its metabolites play important roles in various intestinal mucosal diseases, such as inflammatory bowel disease (IBD), allergic disease, and cancer. Therefore, studies on ILCs and their interaction with the gut microbiota have great clinical significance owing to their potential for identifying pharmacotherapy targets for multiple related diseases. This review expounds on the progress in research on ILCs differentiation and development, the biological functions of the intestinal microbiota, and its interaction with ILCs in disease conditions in order to provide novel ideas for disease treatment in the future.
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Microbioma Gastrointestinal , Humanos , Inmunidad Innata , Inmunidad Mucosa , Mucosa Intestinal , Células Asesinas NaturalesRESUMEN
Cancer heterogeneity has posed a great challenge to traditional cancer treatment, with the reappearance of cancer heterogeneity of inter and intra patients being especially critical. Based on this, personalized therapy has emerged as significant research focus in recent and even future years. Cancer-related therapeutic models are developing, including cell lines, patient-derived xenografts, organoids, etc. Organoids are three-dimensional in vitro models emerged in the past dozen years and are able to reproduce the cellular and molecular composition of the original tumor. These advantages demonstrate the great potential for patient-derived organoids to develop personalized anticancer therapies, including preclinical drug screening and the prediction of patient treatment response. The impact of microenvironment on cancer treatment cannot be underestimated, and the remodeling of microenvironment also allows organoids to interact with other technologies, among which organs-on-chips is a representative one. This review highlights the use of organoids and organs-on-chips as complementary reference tools in treating colorectal cancer from the perspective of clinical efficacy predictability. We also discuss the limitations of both techniques and how they complement each other well.
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Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3'-sialyllactose (3'-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt+ regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3'-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3'-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt+ Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns.
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Diabetes Gestacional , Microbioma Gastrointestinal , Preescolar , Recién Nacido , Lactante , Femenino , Embarazo , Humanos , Animales , Ratones , Linfocitos T Reguladores , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Madres , Leche Humana , BacteriasRESUMEN
BACKGROUND: Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system. PURPOSE: We established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms. METHODS: First, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied. RESULTS: Probiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier. CONCLUSION: This is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.
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Microbioma Gastrointestinal , Probióticos , Reishi , Animales , Ratones , Fermentación , Probióticos/farmacología , Probióticos/uso terapéutico , Ciclofosfamida/efectos adversos , Inmunidad , Terapia de Inmunosupresión , SemillasRESUMEN
To date, colorectal cancer (CRC) still has limited therapeutic efficacy and poor prognosis and there is an urgent need for novel targets to improve the outcome of CRC patients. The highly conserved ubiquitination modification mediated by E3 ubiquitin ligases is an important mechanism to regulate the expression and function of tumor promoters or suppressors in CRC. In this review, we provide an overview of E3 ligases in modulating various biological processes in CRC, including proliferation, migration, stemness, metabolism, cell death, differentiation and immune response of CRC cells, emphasizing the pluripotency of E3 ubiquitin ligases. We further focus on the role of E3 ligases in regulating vital cellular signal pathways in CRC, such as Wnt/ß-catenin pathway and NF-κB pathway. Additionally, considering the potential of E3 ligases as novel targets in the treatment of CRC, we discuss what aspects of E3 ligases can be utilized and exploited for efficient therapeutic strategies.
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BACKGROUND: During the tumourigenesis and development of colorectal cancer (CRC), the inactivation of tumour suppressor genes is closely involved, although detailed molecular mechanisms remain elusive. Accumulating studies, including ours, have demonstrated that basic leucine zipper transcription factor ATF (activating transcription factor)-like 2 (BATF2) is a capable tumour suppressor that localises in the nucleus. However, its different subcellular localisation, potential functions and underlying mechanisms are unclear. METHODS: The translocation of BATF2 and its clinical relevance were detected using CRC samples, cell lines and xenograft nude mice. Candidate BATF2-binding proteins were screened using co-immunoprecipitation, quantitative label-free liquid chromatography-tandem mass spectrometry proteomic analysis, Western blotting and immunofluorescence. Recombinant plasmids, point mutations and siRNAs were applied to clarify the binding sites between BATF2 and chromosome region maintenance 1 (CRM1). RESULTS: The present study found that BATF2 was mainly localised in the cytoplasm, rather than nucleus, of CRC cells in vitro and in vivo, while cytoplasmic BATF2 expression was inversely correlated with the prognosis of CRC patients. Furthermore, we identified the nuclear export and subsequent ubiquitin-mediated degradation of BATF2 in CRC cells. Mechanistically, a functional nuclear export sequence (any amino acid) was characterised in BATF2 protein, through which BATF2 bound to CRM1 and translocated out of nucleus, ultimately enhancing CRC growth via inducing activator protein 1 (AP-1)/cyclin D1/phosphorylated retinoblastoma protein (pRb) signalling pathway. Additionally, nuclear export of BATF2 can be retarded by the mutation of NES in BATF2 or the knockdown of CRM1, whereas CRM1 expression was negatively associated with nuclear BATF2 expression and the prognosis of CRC patients. CONCLUSION: These findings revealed the biological effects and underlying mechanisms of cytoplasmic localisation of BATF2. Furthermore, suppressing nuclear export of BATF2 via mutating its NES region or inhibiting CRM1 expression may serve as a promising therapeutic strategy against CRC.
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Neoplasias Colorrectales , Carioferinas , Animales , Humanos , Ratones , Transporte Activo de Núcleo Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Carioferinas/genética , Carioferinas/química , Carioferinas/metabolismo , Ratones Desnudos , Proteómica , Proteína Exportina 1RESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease, in addition, gut microbiota plays an important role in the etiology of RA. However, our understanding of alterations to the gut fungal microbiota in Chinese population with RA is still limited. METHODS: Serum samples were obtained from 62 patients with RA, and 39 age- and gender-matched healthy controls (HCs). Fecal samples were obtained from 42 RA patients and 39 HCs. Fecal fungal microbiota targeting internal transcribed spacer region 2 (ITS2) rRNA genes was investigated using MiSeq sequencing, as well as their associations with some diagnostic biomarkers for RA. RESULTS: Our results showed that the fungal diversity did not alter in RA patients but taxonomic composition of the fecal fungal microbiota did. The gut mycobiota of RA patients was characterized by decreased abundance of Pholiota, Scedosporium, and Trichosporon. The linear discriminant analysis (LDA) effect size analysis (LEfSe) analysis identified several RA-enriched fungal genera, which were positively correlated with most RA biomarkers. Furthermore, since RA is an age- and gende-related disease, we classified RA patients into subgroups with age and gender and analyzed the sequencing results. Our data demonstrated that Wallemia and Irpex were the most discriminatory against RA patients over 60 years old, while Pseudeurotiaceae was the most discriminatory against female RA patients. CONCLUSIONS: The case-control study presented here confirmed the alterations of gut fungal microbiota in Chinese patients with RA, and we speculated that the fungal dysbiosis may contribute to RA development.
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Artritis Reumatoide , Microbioma Gastrointestinal , Micobioma , Humanos , Femenino , Persona de Mediana Edad , Microbioma Gastrointestinal/genética , Estudios de Casos y Controles , Artritis Reumatoide/diagnóstico , BiomarcadoresRESUMEN
BACKGROUND: Second primary cancer (SPC) after primary colorectal cancer (CRC), emerges as a novel challenge for cancer prevention with pronounced differences between female and male patients. METHODS: This was a retrospective study of 140 907 CRC survivors from the surveillance, epidemiology, and end results program database. Competing risk models and nomograms were constructed to predict the risk of SPCs, which were assessed with the C-Index, calibration and decision curve analysis. RESULTS: The 10-year cumulative incidence of SPC was higher in male than in female CRC survivors. The top five common SPCs in female CRC survivors were colorectal, breast, lung and bronchus, corpus and uterus and pancreatic cancers, while in male were prostate, colorectal, lung and bronchus, urinary cancer and melanoma of the skin. Breast and prostate were the most common sites for the development of SPCs after CRC. Older age, stage I and surgery were common risk factors for SPCs in both female and male. The nomogram for predicting the risk of developing SPC-breast cancer in female patients included age, race, site, histology grade, surgery, chemotherapy and stage. However, the model of predicting SPC-prostate cancer in male patients included age, race, site, size, surgery, chemotherapy, radiation and stage. Notably, the nomograms were validated to have a precise discriminative ability, accuracy and clinical effectiveness. CONCLUSIONS: The study surveyed the characteristics of CRC survivors with a particular focus on the incidence of SPC. The models could help supervise the development of a second breast or prostate cancer in female or male CRC survivors.
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Neoplasias Colorrectales , Neoplasias Primarias Secundarias , Neoplasias de la Próstata , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/epidemiología , Humanos , Incidencia , Masculino , Neoplasias Primarias Secundarias/epidemiología , Neoplasias de la Próstata/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Programa de VERFRESUMEN
Background: Previous studies have revealed an increased risk of second primary malignancies (SPMs) after colorectal cancer (CRC); however, no previous investigation has quantified differences in the risk of SPMs based on the histological subtypes of first primary CRC. Methods: Patients diagnosed with first primary CRC between 2000 and 2011 were identified from the Surveillance, Epidemiology, and End Results cancer registries. The patients were divided into three cohorts: classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC). Standardized incidence ratios were calculated to assess the risk of SPMs among the patients. Results: Overall risk of SPMs was significantly higher among patients with three histological subtypes of CRC than in the general population. The risk of esophagus cancer was significantly increased in SRCC. The risk of small intestine, colon and rectum, and corpus uteri cancers was high in three histological subtypes, with the highest risk observed in SRCC, followed by MA. Increased risks of second stomach, uterus, urinary bladder, kidney, and thyroid cancers were only observed in CA patients, while increased risk of second renal pelvis cancer was limited to MA patients. Furthermore, the high overall risk of SPMs in CA patients persisted regardless of clinicopathological factors. After surgery combined with chemotherapy treatment, CA patients were more prone to developing second small intestine, colon and rectum cancers than those treated with surgery only. A lower second prostate cancer risk was observed in rectal CA patients treated with surgery combined with radiotherapy than in patients treated with surgery only. Conclusion: The present study revealed that the risk of developing SPMs after CRC varied based on the histological subtypes of the first primary CRC. Although the mechanisms underlying the observed patterns of SPM risk remain unknown, the study provided insights into future cancer surveillance based on the histological subtypes of CRC.
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Alternative splicing (AS) is an important event that contributes to posttranscriptional gene regulation. This process leads to several mature transcript variants with diverse physiological functions. Indeed, disruption of various aspects of this multistep process, such as cis- or trans- factor alteration, promotes the progression of colorectal cancer. Therefore, targeting some specific processes of AS may be an effective therapeutic strategy for treating cancer. Here, we provide an overview of the AS events related to colorectal cancer based on research done in the past 5 years. We focus on the mechanisms and functions of variant products of AS that are relevant to malignant hallmarks, with an emphasis on variants with clinical significance. In addition, novel strategies for exploiting the therapeutic value of AS events are discussed.
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Empalme Alternativo/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , ARN Mensajero/genética , Animales , Apoptosis/genética , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/terapia , Humanos , Procesamiento Proteico-Postraduccional , ARN Mensajero/metabolismo , Empalmosomas/metabolismoRESUMEN
BACKGROUND: Some significant differences exist between the outcomes of left- and right-sided colon cancer patients. The presence of nodal metastases is a critical prognostic factor, especially in the absence of distant metastasis. Our research studied the lymph nodes status of left- and right-sided colon cancer patients to determine the influence of this factor on prognosis. METHODS: Our data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We used the chi-square test to analyze the clinicopathological characteristics. The X-tile program was adopted to acquire optimal cutoff points of lymph node index. Kaplan-Meier curves were used to analyze prognosis and multivariate Cox regression models were performed to identify the independent factors associated with survival. Nomograms were built to predict the overall survival of patients, Harrell's C-index and calibration plots were used to validate the nomograms. RESULTS: The study included 189,941 patients with colon cancer without metastasis (left 69,885, right 120,056) between 2004 and 2015. There are more patients with adequate examined lymph nodes in right-sided. Lymph node status in patients with right colon cancer has a more significant impact on the risk of death. LODDS (C-index: 0.583; AIC: 6875.4) was used to assess lymph node status. The nomograms showed that lymph node status was the main factor to predict the outcome in right-sided colon patients. CONCLUSIONS: The influence of lymph node status on predicting prognosis is significantly different between patients with left and right colon cancer without metastasis. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients.
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Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Metástasis Linfática/patología , Anciano , China , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Programa de VERFRESUMEN
Deregulation of many homeobox genes has been observed in various cancers and has caused functional implications in the tumor progression. In this review, we will focus on the roles of the human muscle segment homeobox (MSX) transcription factor family in the process of tumorigenesis. The MSX transcription factors, through complex downstream regulation mechanisms, are promoters or inhibitors of diverse cancers by participating in cell proliferation, cell invasion, cell metastasis, cell apoptosis, cell differentiation, drug resistance of tumors, maintenance of tumor stemness, and tumor angiogenesis. Moreover, their upstream regulatory mechanisms in cancers may include: gene mutation and chromosome aberration; DNA methylation and chromatin modification; regulation by non-coding RNAs; regulation by other transcription factors and post-translational modification. These mechanisms may provide a better understanding of why MSX transcription factors are abnormally expressed in tumors. Notably, intermolecular interactions and post-translational modification can regulate the transcriptional activity of MSX transcription factors. It is also crucial to know what affects the transcriptional activity of MSX transcription factors in tumors for possible interventions in them in the future. This systematic summary of the regulatory patterns of the MSX transcription factor family may help to further understand the mechanisms involved in transcriptional regulation and also provide new therapeutic approaches for tumor progression.