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1.
Front Oncol ; 14: 1280805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601767

RESUMO

Hepatocellular carcinoma is a rather common malignant tumor. Most patients with hepatocellular carcinoma receive their diagnosis at an advanced stage, at which surgical resection is no longer appropriate. A growing body of research has demonstrated the value of convention therapy for patients with intermediate-stage hepatocellular carcinoma, while specific application protocols and treatment guidelines are not well developed. Emerging clinical researches suggest that a tyrosine kinase inhibitor in combination with an immune checkpoint inhibitor is a reasonable strategy for unresectable hepatocellular carcinoma. However, there are relatively few reports on the efficacy of apatinib and camrelizumab in the treatment of hepatocellular carcinoma. We were able to successfully remove one patient's hepatocellular carcinoma after 8 cycles of conversion therapy with apatinib (250 mg orally every day) and camrelizumab (200 mg intravenously every 2 weeks). The patient continued to receive the same dose of 16 cycles of apatinib and camrelizumab after hepatectomy. By the time of this study, the patient has completed 18 months of follow-up, and no tumor recurrence or metastasis was found in tumor markers and imaging examinations. Apatinib in combination with camrelizumab is an effective therapy for the treatment of advanced hepatocellular carcinoma, and surgical resection after this conversion therapy may provide patients with long-term oncological benefits. However, this requires more samples to validate the conclusion.

4.
Medicine (Baltimore) ; 102(35): e34678, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37657054

RESUMO

BACKGROUND: To evaluate the efficacy and safety of acupuncture by systematically reviewing the literature on colorectal cancer resection. METHODS: Seven electronic databases were searched from inception to February 28, 2023. Randomized controlled trials on acupuncture in patients after CRC resection were included. Two reviewers independently selected relevant trials, extracted data, and assessed the risk of bias. A random-effects meta-analysis model was used to obtain summary effect estimates. The data were pooled and analyzed using RevMan 5.3. The heterogeneity of selected studies was evaluated by evaluating the I-squared (I2) statistics. RESULTS: Twenty-two studies with 1878 patients were included. Results of the meta-analysis showed there was a low level evidence that acupuncture may improve early postoperative symptoms, such as time to first flatus (n = 876, MD -0.77h, 95% CI -1.22 to -0.33 h, I2 = 89%), time to first bowel movement (n = 671, MD -1.41h, 95% CI -2.20 to -0.63 h, I2 = 95%), time to first defecation (n = 556, MD -1.03h, 95% CI -1.88 to -0.18 h, I2 = 95%), and nausea/vomiting (n = 1488, RR 0.72, 95% CI 0.59-0.89, I2 = 49%) compared with usual care and sham acupuncture. However, there were no statistically significant differences in postoperative pain (n = 1188, MD-0.21, 95% CI -0.59 to 0.17, I2 = 74%). And there was no sufficient evidence of improving long-term functional outcomes. There was substantial heterogeneity across trials. The adverse events associated with acupuncture stimulation were minor in include studies. CONCLUSION SUBSECTIONS: There is currently low-level evidence supporting the use of acupuncture on postoperative symptoms for patients after colorectal cancer resection. More investigations should be established based on the STRICTA statement strictly.


Assuntos
Terapia por Acupuntura , Neoplasias Colorretais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor Pós-Operatória , Bases de Dados Factuais , Neoplasias Colorretais/cirurgia
5.
Front Surg ; 10: 1193265, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325419

RESUMO

Background: Prolapsing technique is a type of natural orifice specimen extraction surgery that can overcome the difficulty of precise transection of the distal rectum and subsequent anastomosis in a narrow pelvic space. Currently, protective ileostomy is widely utilized in low anterior resection for low rectal cancer, which may reduce the severe consequences caused by anastomotic leakage. The study aimed to combine the prolapsing technique with a one-stitch method of ileostomy and evaluate the surgical outcomes. Methods: A retrospective analysis was conducted on patients with low rectal cancer who underwent protective loop ileostomy in laparoscopic low anterior resection between January 2019 and December 2022. The patients were divided into prolapsing technique combined with the one-stitch method of ileostomy (PO) group and traditional method (TM) group, and the intraoperative details and early postoperative outcomes of the two groups were measured. Results: A total of 70 patients met the inclusion criteria, including 30 patients who underwent PO and 40 patients who underwent the traditional procedure. The PO group had a shorter total operative time than the TM group (197.8 ± 43.4 vs. 218.3 ± 40.6 min, P = 0.047). The time of intestine function recovery in the PO group was shorter than that in the TM group (24.6 ± 3.8 vs. 32.7 ± 5.4 h, P < 0.001). Compared with the TM group, the average VAS score was significantly lower in the PO group (P < 0.001). The incidence of anastomotic leakage in the PO group was significantly lower than that in the TM group (P = 0.034). The operative time of loop ileostomy was 2.0 ± 0.6 min in the PO group, which was significantly less than 15.1 ± 2.9 min in the TM group. Skin irritation was observed in 2 patients in the PO group and 10 patients in the TM group; therefore, there was a significant difference (P = 0.044). Conclusion: This method is safe and feasible, which reduces the technical difficulty and achieves rapid postoperative recovery with few complications.

6.
Photodiagnosis Photodyn Ther ; 42: 103599, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37156455

RESUMO

BACKGROUND: To perform a systematic review of the safety and effectiveness of fluorescence laparoscopy-guided precise hepatectomy. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to December 1, 2022, using the search terms "indocyanine green," "ICG," "infracyanine green," "laparoscopy," "liver resection," and "hepatectomy." After performing a methodological quality assessment of the included studies, the overall results were subjected to meta-analysis using Review Manager 5.3. RESULTS: After screening, the meta-analysis included a total of 13 articles. The studies included 1,115 patients who were grouped into the fluorescence laparoscopy (490 patients) and conventional laparoscopy (625 patients) groups. All articles included in the meta-analysis were of high quality. The results of the meta-analysis revealed that compared to the conventional laparoscopy group, the fluorescence laparoscopy group had a higher R0 resection rate (odds ratio=4.03, 95% confidence interval [1.50, 10.83], P = 0.006), lower blood transfusion rate (odds ratio=0.46, 95% confidence interval [0.21, 0.97], P = 0.04) and lower blood loss (mean difference=-36.58; 95% confidence interval [-59.75, -13.41], P = 0.002). However, the length of hospital stay, operative time, and incidence of postoperative complications did not differ significantly between both groups (P>0.05). CONCLUSION: Compared to conventional laparoscopy, fluorescence laparoscopy provides better application effects in hepatectomy. The surgical procedure has demonstrated good safety and feasibility, which make it worthy of popularization.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Fotoquimioterapia , Humanos , Hepatectomia/métodos , Fluorescência , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia
7.
Reprod Sci ; 30(1): 233-246, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35715550

RESUMO

Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility, but its diagnosis biomarkers with high sensitivity and specificity are largely unknown. Transcription factors (TFs) play essential roles in many pathological processes in different diseases. Herein, we aimed to identify the TFs showing high diagnosis ability for NOA through machine learning algorithms. The transcriptome data of the testicular tissue from 11 control and 47 NOA subjects were set as the training dataset; meanwhile, 1665 TFs were retrieved from the HumanTFDB. Through the feature extraction methods, including genomic difference analysis, Lasso, Boruta, SVM-RFE, and logistic regression, ETV2, TBX2, and ZNF689 were ultimately screened and then were included in the random forest (RF) diagnosis model. The RF model displayed high predictive power in the training (F-measure = 1) and two external validation (n = 31, F-measure = 0.902; n = 20, F-measure = 0.941) cohorts. The seminal plasma and testicular biopsy samples of 20 control and 20 NOA patients were collected from the local hospital, and the expression levels of ETV2, TBX2, and ZNF689 were measured via RT-qPCR and immunohistochemistry. The RF model could also distinguish the NOA samples in the local cohort (F-measure = 0.741). Single-cell RNA sequencing analysis, which was based on the 432 testicular cell samples from an NOA patient, showed that ETV2, TBX2, and ZNF689 were all significantly associated with spermatogenesis. In all, a 3-TF random forest diagnosis model was successfully established, providing novel insights into the latent mechanisms of NOA.


Assuntos
Proteínas Reguladoras de Apoptose , Azoospermia , Proteínas com Domínio T , Fatores de Transcrição , Humanos , Masculino , Proteínas Reguladoras de Apoptose/genética , Azoospermia/diagnóstico , Azoospermia/genética , Azoospermia/patologia , Algoritmo Florestas Aleatórias , Testículo/metabolismo , Fatores de Transcrição/genética , Proteínas com Domínio T/genética
8.
Medicine (Baltimore) ; 101(35): e30427, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107595

RESUMO

RATIONALE: Superior mesenteric artery (SMA) syndrome, also known as Wilkie syndrome, is a rare benign disease characterized by small bowel obstruction due to compression of the third portion of the duodenum by the SMA and the abdominal aorta. However, SMA syndrome after colectomy is extremely rare, establishing a clear diagnosis and formulating a treatment plan may be challenging for surgeons. PATIENT CONCERNS: A 64-year-old male with multiple colon polyposis and constipation underwent laparoscopic subtotal colectomy with cecal-rectal anastomosis. On the seventh postoperative day, he started vomiting and complained of abdominal bloating. DIAGNOSIS: An upper gastrointestinal series, computed tomography scan and computed tomography angiography confirmed the diagnosis of SMA syndrome. INTERVENTIONS: Gastric decompression, nasojejunal tube feeding and parenteral nutrition were performed. OUTCOMES: After 3 weeks of conservative treatment, the patient showed no clinical improvement in symptoms. Subsequently, he suffered from gastrointestinal hemorrhage, deep venous thrombosis of the lower extremity and cerebral hemorrhage successively. Unfortunately, the patient eventually died. LESSONS: Surgeons should be aware of the fact that SMA syndrome can occur after colectomy. Every attempt should be made to correct and avoid any predisposing factors perioperatively. Prompt diagnosis of SMA syndrome after colectomy and appropriate early intervention reduce mortality.


Assuntos
Síndrome da Artéria Mesentérica Superior , Angiografia , Colectomia/efeitos adversos , Duodeno/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome da Artéria Mesentérica Superior/diagnóstico , Síndrome da Artéria Mesentérica Superior/etiologia , Síndrome da Artéria Mesentérica Superior/terapia , Tomografia Computadorizada por Raios X/efeitos adversos
9.
Front Oncol ; 12: 929838, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059676

RESUMO

Background: ACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism-linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers. Methods: The expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan-Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)-KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib. Results: KIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan-Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells. Conclusion: ACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.

10.
World J Clin Cases ; 10(21): 7409-7414, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-36158018

RESUMO

BACKGROUND: Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion with a complete necrotic core and a clear fibrous capsule containing elastic fibers. We present the case of a patient with a radiographic computed tomography (CT) finding of "ring"-like annular calcification within the lesion and postoperative pathologic diagnosis of necrotic nodules wrapped by dense fibers in liver tissue, as well as the patient's subsequent management and outcome. CASE SUMMARY: A 38-year-old Chinese woman with a history of systemic lupus erythematosus treated with prednisone and hydroxychloroquine, without any symptoms, was found to have hepatic space-occupying lesions by imaging examination at a health examination. A subsequent CT scan suggested a space-occupying lesion of the liver with annular calcification, which was not defined to be benign or malignant. After that, a laparoscopic hepatic space-occupying resection was performed. The postoperative pathological diagnosis was necrotic nodules wrapped by dense fibers in the liver tissue, and the final diagnosis was SNNL. The patient had an uneventful postoperative recovery. CONCLUSION: There is a "ring"-like calcification in SNNL. This patient had a history of systemic lupus erythematosus, without a history of parasite infection, trauma, or tumor. Therefore, whether the etiology and pathological changes of SNNL are related to rheumatic immune diseases remains to be investigated.

11.
Dis Markers ; 2022: 2143892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280438

RESUMO

Immunosenescence refers to the immune system undergoing a series of degenerative changes with advancing age and is tightly associated with the initiation and progression of cancers. However, the immunosenescence-related genes as critical biomarkers for bladder cancer (BLCA) have not been systematically analyzed. We retrieved the immunosenescence-related genes from the public database and verified their association with hallmarks of immunosenescence based on The Cancer Genome Atlas (TCGA) cohort. Through gene pairing, Lasso, and univariate Cox regression, an 8-gene pair model was constructed to evaluate the overall survival of BLCA, which was then validated in the training cohort (P < 0.001, n = 396), two external validation cohorts (P < 0.05, n = 165; P < 0.001, n = 224), and local samples (P < 0.05, n = 10). We also downloaded the clinical information and gene expression matrices of other 32 different cancers from TCGA. The established model showed significant predictive value for the prognosis in 15 cancers (P < 0.05). The risk model could also serve as a promising predictor for immunotherapeutic response, which has been verified by the TIDE algorithm (P < 0.05), IMvigor210 dataset (P < 0.01, n = 298), and other two datasets correlated with immunotherapy (P < 0.05, n = 56; P = 0.17, n = 27). The TCGA dataset, in vitro cell experiments, and pan-cancer analysis displayed that the gene signature was associated with cisplatin sensitivity (P < 0.05). Overall, we proposed a novel immunosenescence-related gene signature to predict prognosis, immunotherapeutic response, and cisplatin sensitivity of BLCA, which were validated in different independent cohorts, local samples, and pan-cancer analyses.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Imunossenescência/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transcriptoma , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade
12.
J Chromatogr Sci ; 60(5): 414-422, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34905773

RESUMO

Qixue Shuangbu Prescription (QSP) has been widely applied in the treatment of chronic heart failure (CHF). Previous clinical studies have found that the efficacy of processed QSP was significantly enhanced in the treatment of CHF. We have identified and analyzed the nonvolatile components before and after processing of QSP, and predicted the mechanism of synergistic effect after processing in the treatment of CHF. However, the synergistic mechanism of processed QSP caused by the difference of volatile components was still unclear. In this study, we developed a method of needle trap device coupled with gas chromatography-triple quadrupole mass spectrometry to elucidate the difference of volatile components between crude and processed QSP. The established method has been used to identify 104 volatile compounds in crude and processed QSP. The results of multivariate data showed 38 differential compounds were screened as potential markers, which would further explain the mechanism of processing synergistic effect of processed QSP. This study successfully developed the method to elucidate its processing mechanism based on the difference of volatile compositions between crude and processed QSP for the first time, and it would provide a novel analytical strategy for the impacts of different processing methods on main volatile compounds in traditional Chinese medicine.


Assuntos
Medicamentos de Ervas Chinesas , Compostos Orgânicos Voláteis , Biomarcadores , Medicamentos de Ervas Chinesas/química , Cromatografia Gasosa-Espectrometria de Massas , Medicina Tradicional Chinesa , Prescrições , Compostos Orgânicos Voláteis/análise
13.
Cancer Cell Int ; 21(1): 660, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895217

RESUMO

BACKGROUND: In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. METHODS: Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. RESULTS: ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/ß-catenin pathway. CONCLUSIONS: This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.

14.
Aging (Albany NY) ; 13(23): 25153-25179, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862329

RESUMO

Circadian dysregulation involves malignant tumor initiation and progression, but the understanding of circadian rhythm's roles in bladder cancer (BCa) remains insufficient. The circadian rhythm-related genes were collected and clustered based on the Cancer Genome Atlas (TCGA), and the clustering was significantly associated with the prognosis and risk clinicopathological features. Through genomic difference analysis and gene pairing, a circadian rhythm-related signature was successfully established. Kaplan-Meier survival analysis and time-dependent receiver operating curves displayed that the prognosis model was a reliable prognosis biomarker both in the training cohort (n = 396, P = 2.687e-10) and external validation cohort (n = 224, P = 1.45e-02). The patients with high risk have high immune infiltration and high expression of immune checkpoint genes, which partly account for the poor prognosis. TIDE algorithm and the validation in IMvigor210 cohort indicated that the risk signature was a promising marker for the immunotherapeutic response. The risk model could also predict the therapeutic response of cisplatin, which was validated in the Genomics of Drug Sensitivity in Cancer database (P = 0.0049), TCGA (P = 0.038), and T24 BCa cells treated with cisplatin. The functional enrichment showed the risk model was significantly correlated with some malignant phenotypes, such as angiogenesis, epithelial-mesenchymal transition, and KRAS signaling pathway. Totally, we proposed a novel circadian rhythm-related signature for prognosis evaluation, which also helped to predict the immune infiltration and cisplatin sensitivity in BCa.


Assuntos
Antineoplásicos/uso terapêutico , Ritmo Circadiano/genética , Cisplatino/uso terapêutico , Neoplasias da Bexiga Urinária/genética , Idoso , Algoritmos , Feminino , Humanos , Proteínas de Checkpoint Imunológico/metabolismo , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral , Masculino , Prognóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade
15.
Aging (Albany NY) ; 13(21): 24219-24235, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34738918

RESUMO

Non-obstructive azoospermia (NOA) is among the most severe factors for male infertility, but our understandings of the latent biological mechanisms remain insufficient. The single-cell RNA sequencing (scRNA-seq) data of 432 testicular cells isolated from the patient with NOA was analyzed, and the cell samples were grouped into 5 cell clusters. A sum of 455 cell markers was identified and then included in the protein-protein interaction network. The Top 5 most critical genes in the network, including CCT8, CDC6, PSMD1, RPS4X, RPL36A, were selected for the diagnosis model construction through the random forest (RF). The RF model was a strong classifier for NOA and obstructive azoospermia (OA), which was validated in the training cohort (n = 58, AUC = 1) and external validation cohort (n = 20, AUC = 0.9). We collected the seminal plasma samples and testicular biopsy samples from 20 OA and 20 NOA cases from the local hospital, and the gene expression was detected via Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) and Immunohistochemistry. The RF model also exhibited high accuracy (AUC = 0.725) in the local cohort. In summary, a novel gene signature was developed and externally validated based on scRNA-seq analysis, providing some new biomarkers to uncover the underlying mechanisms and a promising clinical tool for diagnosis in NOA.


Assuntos
Azoospermia/diagnóstico , Azoospermia/genética , Aprendizado de Máquina , RNA-Seq/métodos , Análise de Célula Única/métodos , Adulto , Diagnóstico por Computador , Humanos , Masculino , Mapas de Interação de Proteínas/genética , Transcriptoma/genética
16.
Cell Death Discov ; 7(1): 209, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376644

RESUMO

In China, hepatocellular carcinoma (HCC) is considered a malignant tumor with poor prognosis, frequent metastasis, and a high relapse rate. Telocytes (TCs) participate in tumorigenic, invasive, and migratory processes by secreting functional proteins and transmitting cell-to-cell information, but their functions in HCC are still unknown. TC counts and MMP9 expression in liver cancer tissues were measured using immunohistochemistry, western blotting, and RT-PCR. Primary TCs from liver para-cancer tissues were cultured in vitro. To verify the role of TCs in HCC, a metastatic cancer animal model was established using three types of liver cancer cell lines in vivo. TCs promoted HCC cell metastasis by MMP9 expression in vitro and in vivo. Platelet-derived growth factor-alpha (PDGF-α), secreted by HCC cells, activated the Ras/ERK signaling pathway in TCs, thereby increasing MMP9 expression; Moreover, miR-942-3p suppressed MMP9 expression in TCs. Our results reveal the role of TCs in HCC and the mechanisms by which they elicit their effects, and they may serve as novel prognostic markers for HCC.

17.
Aging (Albany NY) ; 13(15): 19415-19441, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34339395

RESUMO

Intra-tumor heterogeneity (ITH) was a potential mechanism of progression and drug resistance in bladder cancer (BCa). However, the understanding of ITH in BCa remains insufficient. Single-cell RNA sequencing (scRNA-seq) profiles of 2075 cells were analyzed, and 2940 cell markers were screened. The ITH of 396 cases was evaluated, and 96 ITH-related genes were identified. Based on the gene-pair strategy, 96 genes were cyclically paired, and an 8-gene-pair model was successfully established to evaluate the overall survival of BCa through Lasso and multivariate Cox regressions. The risk model showed high predictive value in the training dataset (n = 396, p = 0) and external validation datasets (n = 165, p = 2.497e-02; n = 224, p = 3.423e-02). The model was also valuable for the prediction of clinical treatment outcomes. Totally, a prognostic model based on scRNA-seq and ITH was successfully constructed and validated in large cohorts, providing novel clues for ITH study of BCa.


Assuntos
Heterogeneidade Genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , RNA-Seq , Análise de Célula Única , Neoplasias da Bexiga Urinária/patologia
18.
Dis Markers ; 2021: 1031906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239619

RESUMO

The tight relationship between ferroptotic cell death and immune response demonstrated by recent studies enlightened us to detect the underlying roles of ferroptosis-related long noncoding RNAs (frlncRNAs) in the tumor microenvironment of bladder cancer (BCa). We collected 121 ferroptosis regulators from previous studies. Based on their expression values, 408 cases with BCa were clustered. The patients in different clusters showed diverse immune infiltration, immunotherapy response, and chemotherapy effectiveness, revalidating the tight correlation with ferroptosis and tumor immunity. Through differential, coexpression, Kaplan-Meier, Lasso, and Cox analysis, we developed a 22-lncRNA-pair signature to predict the prognosis of BCa based on gene-pair strategy, where there is no need for definite expression values. The areas under the curves are all over 0.8. The risk model also helped to predict immune infiltration, immunotherapeutic outcomes, and chemotherapy sensitivity. Totally, the prognostic assessment model indicated a promising predictive value, also providing clues for the interaction between ferroptosis and BCa immunity.


Assuntos
Biomarcadores Tumorais , Regras de Decisão Clínica , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Área Sob a Curva , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Feminino , Seguimentos , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Análise de Sobrevida , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade
19.
Artigo em Inglês | MEDLINE | ID: mdl-33688358

RESUMO

INTRODUCTION: Traditional Chinese medicine (TCM) believes that the pathogenic factors of colorectal cancer (CRC) are "deficiency, dampness, stasis, and toxin," and Fuzheng-Jiedu Decoction (FJD) can resist these factors. In this study, we want to find out the potential targets and pathways of FJD in the treatment of CRC and also explain from a scientific point of view that FJD multidrug combination can resist "deficiency, dampness, stasis, and toxin." METHODS: We get the composition of FJD from the TCMSP database and get its potential target. We also get the potential target of colorectal cancer according to the OMIM Database, TTD Database, GeneCards Database, CTD Database, DrugBank Database, and DisGeNET Database. Subsequently, PPI analysis, KEGG pathways analysis, and GO biological processes analysis were carried out for the target of FJD in the therapy of colorectal cancer. In addition, we have also built a relevant network diagram. RESULTS: In this study, we identified four core compounds of FJD in the therapy of colorectal cancer, including quercetin, kaempferol, beta-sitosterol, and stigmasterol. At the same time, we also obtained 30 core targets, including STAT3, INS, TP53, VEGFA, AKT1, TNF, IL6, JUN, EGF, CASP3, MAPK3, MAPK1, MAPK8, SRC, IGF1, CCND1, ESR1, EGFR, PTEN, MTOR, FOS, PTGS2, CXCL8, HRAS, CDH1, BCL2L1, FN1, MMP9, ERBB2, and JAK2. FJD treatment of colorectal cancer mainly involves 112 KEGG pathways, including FoxO (hsa04068) signaling pathway, PI3K-Akt (hsa04151) signaling pathway, HIF-1 (hsa04066) signaling pathway, T cell receptor (hsa04660) signaling pathway, and ErbB (hsa04012) signaling pathway. At the same time, 330 GO biological processes were summarized, including cell proliferation, cell apoptosis, angiogenesis, inflammation, and immune. CONCLUSIONS: In this study, we found that FJD can regulate cell proliferation, apoptosis, inflammation and immunity, and angiogenesis through PI3K-Akt signaling pathway to play an anti-CRC effect.

20.
Acta Histochem ; 123(2): 151681, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33493960

RESUMO

Telocytes, which possess distinct body shapes and long telopodes, are allocated in the vascular wall. As a fundamental cell type, telocytes construct a three-dimensional network to form a support structure for the artery. This study aims to characterize the morphology and ultrastructure of telocytes in atherosclerotic arteries. ApoE gene-deficient mice were selected as the atherosclerosis animal model and fed a high-fat diet for at least 12 weeks, and immunofluorescence assays and transmission electron microscopy techniques were used to observe changes in telocytes in atherosclerotic arteries. By immunofluorescence staining, CD34, CD117 and PDGFR-α were positive compared with negative CD28/vimentin in telocytes in the atherosclerotic carotid artery, and they were distributed in the tunica intima and tunica adventitia. Under transmission electron microscopy, the bodies of telocytes became larger, while telopodes became shorter compared with their normal condition, and a mass of lipidosomes was present during the progression of atherosclerosis. These results demonstrate that immunofluorescence with TEM is the critical method for identifying TCs and that steatosis of TCs is a reason for atherosclerotic artery dysfunction.


Assuntos
Aterosclerose/metabolismo , Artérias Carótidas/metabolismo , Telócitos/metabolismo , Animais , Antígenos CD34/genética , Antígenos CD34/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Imunofluorescência , Masculino , Camundongos , Camundongos Knockout , Microscopia Eletrônica , Microscopia Eletrônica de Transmissão , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo
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