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Cancer Imaging : the Official... Jun 2024This study aimed to evaluate the T2W hypointense ring and T2-FLAIR mismatch signs in gliomas and use these signs to construct prediction models for glioma grading and...
BACKGROUND
This study aimed to evaluate the T2W hypointense ring and T2-FLAIR mismatch signs in gliomas and use these signs to construct prediction models for glioma grading and isocitrate dehydrogenase (IDH) mutation status.
METHODS
Two independent radiologists retrospectively evaluated 207 glioma patients to assess the presence of T2W hypointense ring and T2-FLAIR mismatch signs. The inter-rater reliability was calculated using the Cohen's kappa statistic. Two logistic regression models were constructed to differentiate glioma grade and predict IDH genotype noninvasively, respectively. Receiver operating characteristic (ROC) analysis was used to evaluate the developed models.
RESULTS
Of the 207 patients enrolled (119 males and 88 females, mean age 51.6 ± 14.8 years), 45 cases were low-grade gliomas (LGGs), 162 were high-grade gliomas (HGGs), 55 patients had IDH mutations, and 116 were IDH wild-type. The number of T2W hypointense ring signs was higher in HGGs compared to LGGs (p < 0.001) and higher in the IDH wild-type group than in the IDH mutant group (p < 0.001). There were also significant differences in T2-FLAIR mismatch signs between HGGs and LGGs, as well as between IDH mutant and wild-type groups (p < 0.001). Two predictive models incorporating T2W hypointense ring, absence of T2-FLAIR mismatch, and age were constructed. The area under the ROC curve (AUROC) was 0.940 for predicting HGGs (95% CI = 0.907-0.972) and 0.830 for differentiating IDH wild-type (95% CI = 0.757-0.904).
CONCLUSIONS
The combination of T2W hypointense ring, absence of T2-FLAIR mismatch, and age demonstrate good predictive capability for HGGs and IDH wild-type. These findings suggest that MRI can be used noninvasively to predict glioma grading and IDH mutation status, which may have important implications for patient management and treatment planning.
Topics: Humans; Glioma; Isocitrate Dehydrogenase; Female; Male; Middle Aged; Brain Neoplasms; Retrospective Studies; Neoplasm Grading; Magnetic Resonance Imaging; Adult; Mutation; Genotype; Aged; ROC Curve
PubMed: 38943156
DOI: 10.1186/s40644-024-00726-3 -
World Journal of Surgical Oncology Jun 2024Existing research on chyle leak (CL) after pancreatic surgery is mostly focused on pancreaticoduodenectomy and lacks investigation on total pancreatectomy (TP). This...
BACKGROUND
Existing research on chyle leak (CL) after pancreatic surgery is mostly focused on pancreaticoduodenectomy and lacks investigation on total pancreatectomy (TP). This study aimed to explore potential risk factors of CL and develop a predictive model for patients with pancreatic tumor undergoing TP.
METHODS
This retrospective study enrolled 90 consecutive patients undergoing TP from January 2015 to December 2023 at Peking Union Medical College Hospital. According to the inclusion criteria, 79 patients were finally included in the following analysis. The LASSO regression and multivariate logistic regression analysis were performed to identify risk factors associated with CL and construct a predictive nomogram. Then, the ROC analysis, calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were performed to assess its discrimination, accuracy, and efficacy. Due to the small sample size, we adopted the bootstrap resampling method with 500 repetitions for validation. Lastly, we plotted and analyzed the trend of postoperative drainage volume in CL patients.
RESULTS
We revealed that venous resection (OR = 4.352, 95%CI 1.404-14.04, P = 0.011) was an independent risk factor for CL after TP. Prolonged operation time (OR = 1.473, 95%CI 1.015-2.237, P = 0.052) was also associated with an increased incidence of CL. We included these two factors in our prediction model. The area under the curve (AUC) was 0.752 (95%CI 0.622-0.874) after bootstrap. The calibration curve, DCA and CIC showed great accuracy and clinical benefit of our nomogram. In patients with CL, the mean drainage volume was significantly higher in venous resection group and grade B CL group.
CONCLUSION
Venous resection was an independent risk factor for chyle leak after TP. Patients undergoing vascular resection during TP should be alert for the occurrence of CL after surgery. We then constructed a nomogram consisted of venous resection and operation time to predict the odds of CL in patients undergoing TP.
Topics: Humans; Male; Female; Pancreatic Neoplasms; Retrospective Studies; Middle Aged; Pancreatectomy; Risk Factors; Postoperative Complications; Nomograms; Chyle; Prognosis; Follow-Up Studies; Aged; ROC Curve; Adult
PubMed: 38943154
DOI: 10.1186/s12957-024-03451-0 -
Breast Cancer Research : BCR Jun 2024The cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to...
BACKGROUND
The cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to tumorigenesis. The atypical cell cycle regulator, Spy1 can override cell cycle checkpoints, including those activated by the tumour suppressor p53 which mediates mammary stem cell homeostasis. Spy1 has also been shown to promote expansion of select stem cell populations in other developmental systems. Spy1 protein is elevated during proliferative stages of mammary gland development, is found at higher levels in human breast cancers, and promotes susceptibility to mammary tumourigenesis when combined with loss of p53. We hypothesized that Spy1 cooperates with loss of p53 to increase susceptibility to tumour initiation due to changes in susceptible mammary stem cell populations during development and drives the formation of more aggressive stem like tumours.
METHODS
Using a transgenic mouse model driving expression of Spy1 within the mammary gland, mammary development and stemness were assessed. These mice were intercrossed with p53 null mice to study the tumourigenic properties of Spy1 driven p53 null tumours, as well as global changes in signaling via RNA sequencing analysis.
RESULTS
We show that elevated levels of Spy1 leads to expansion of mammary stem cells, even in the presence of p53, and an increase in mammary tumour formation. Spy1-driven tumours have an increased cancer stem cell population, decreased checkpoint signaling, and demonstrate an increase in therapy resistance. Loss of Spy1 decreases tumor onset and reduces the cancer stem cell population.
CONCLUSIONS
This data demonstrates the potential of Spy1 to expand mammary stem cell populations and contribute to the initiation and progression of aggressive, breast cancers with increased cancer stem cell populations.
Topics: Animals; Female; Mice; Tumor Suppressor Protein p53; Mammary Glands, Animal; Mice, Transgenic; Humans; Cell Cycle Proteins; Neoplastic Stem Cells; Cell Transformation, Neoplastic; Carcinogenesis; Cell Proliferation; Breast Neoplasms; Stem Cells; Cell Cycle; Gene Expression Regulation, Neoplastic
PubMed: 38943151
DOI: 10.1186/s13058-024-01862-1 -
Journal of Ovarian Research Jun 2024This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests,...
BACKGROUND
This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.
METHODS
Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22.
RESULTS
Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F.
CONCLUSIONS
NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.
Topics: Animals; Female; Doxorubicin; Acetylcysteine; Rats; Ovary; Ultrasonography; Uterus; Antibiotics, Antineoplastic
PubMed: 38943148
DOI: 10.1186/s13048-024-01459-4 -
Respiratory Research Jun 2024To detect the expression of autophagy components, p38 MAPK (p38) and phosphorylated forkhead box transcription factor O-1 (pFoxO1) in pulmonary vascular endothelial...
AIMS
To detect the expression of autophagy components, p38 MAPK (p38) and phosphorylated forkhead box transcription factor O-1 (pFoxO1) in pulmonary vascular endothelial cells of chronic thromboembolic pulmonary hypertension (CTEPH) rats and to investigate the possible mechanism through which tissue factor (TF) regulates autophagy.
METHODS
Pulmonary artery endothelial cells (PAECs) were isolated from CTEPH (CTEPH group) and healthy rats (control group (ctrl group)) which were cocultured with TF at different time points including 12 h, 24 h, 48 h and doses including 0 nM,10 nM, 100 nM, 1µM, 10µM, 100µM and cocultured with TFPI at 48 h including 0 nM, 2.5 nM, 5 nM. The expression of forkhead box transcription factor O-1 (FoxO1), pFoxO1, p38, Beclin-1 and LC3B in PAECs was measured. Coimmunoprecipitation (co-IP) assays were used to detect the interaction between FoxO1 and LC3.
RESULTS
The protein expression of p-FoxO1/FoxO1 was significantly lower in the CTEPH groups (cocultured with TF from 0 nM to 100 µM) than in the ctrl group at 12 h, 24 h, and 48 h (P < 0.05) and was significantly lower in the CTEPH groups (cocultured with TFPI from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of p38 in the CTEPH groups treated with 0 nM, 10 nM, 100 nM or 1 µM TF for 48 h significantly increased than ctrl groups (P < 0.05) and was significantly increased in the CTEPH groups (cocultured with TFPI concentration from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of Beclin1 at the same concentration (cocultured with TF from 0 nM to 100 µM) was significantly lower in the CTEPH groups than ctrl groups after 24 h and 48 h (P < 0.05) and was significantly decreased in the CTEPH groups (cocultured with TFPI concentration from 2.5 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of LC3-II/LC3-I at the same concentration (cocultured with TF 0 nM, 1 µM, 10 µM, and 100 µM) was significantly lower in the CTEPH than in the ctrl groups after 12 h (P < 0.05) and was significantly lower in the CTEPH groups (cocultured with TFPI concentration from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). There were close interactions between FoxO1 and LC3 in the control and CTEPH groups at different doses and time points.
CONCLUSION
The autophagic activity of PAECs from CTEPH rats was disrupted. TF, FoxO1 and p38 MAPK play key roles in the autophagic activity of PAECs. TF may regulate autophagic activity through the p38 MAPK-FoxO1 pathway.
Topics: Animals; Autophagy; p38 Mitogen-Activated Protein Kinases; Pulmonary Artery; Rats; Male; Endothelial Cells; Rats, Sprague-Dawley; Cells, Cultured; Thromboplastin; Hypertension, Pulmonary; Pulmonary Embolism; Chronic Disease; Signal Transduction; Forkhead Box Protein O1
PubMed: 38943142
DOI: 10.1186/s12931-024-02886-z -
BMC Medical Genomics Jun 2024Placental hypoxia is hazardous to maternal health as well as fetal growth and development. Preeclampsia and intrauterine growth restriction are common pregnancy...
Placental hypoxia is hazardous to maternal health as well as fetal growth and development. Preeclampsia and intrauterine growth restriction are common pregnancy problems, and one of the causes is placental hypoxia. Placental hypoxia is linked to a number of pregnancy illnessesv. To investigate their potential function in anoxic circumstances, we mimicked the anoxic environment of HTR-8/Svneo cells and performed lncRNA and circRNA studies on anoxic HTR-8/Svneo cells using high-throughput RNA sequencing. The miRNA target genes were predicted by integrating the aberrant expression of miRNAs in the placenta of preeclampsia and intrauterine growth restriction, and a ceRNA network map was developed to conduct a complete transcriptomic and bioinformatics investigation of circRNAs and lncRNAs. The signaling pathways in which the genes were primarily engaged were predicted using GO and KEGG analyses. To propose a novel explanation for trophoblastic organism failure caused by lncRNAs and circRNAs in an anoxic environment.
Topics: Humans; RNA, Circular; RNA, Long Noncoding; Gene Regulatory Networks; Cell Line; RNA-Seq; Cell Hypoxia; Pregnancy; MicroRNAs; Female; Placenta; Trophoblasts; Computational Biology; Gene Expression Profiling
PubMed: 38943134
DOI: 10.1186/s12920-024-01933-4 -
Diagnostic Pathology Jun 2024Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and...
BACKGROUND
Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and comprises > 95% of all LPL cases. Rituximab-based regimens have been predominant in the management of WM. Infusion-related reactions (IRRs) are a primary concern with rituximab, although it is generally better tolerated with less toxicity than conventional anticancer agents. Here, we present an autopsy case of an elderly man who died suddenly after receiving the initial infusion of rituximab for WM/LPL.
CASE PRESENTATION
An 84-year-old man was found dead in his bedroom. He had undergone the initial intravenous rituximab infusion for progressive anemia related to Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) approximately 15 h before death. Although the protocol for rituximab administration and additional medication was considered appropriate, he exhibited several symptoms consistent with infusion-related reactions (IRRs) during the infusion. Autopsy revealed monotonous proliferation of small-to-medium-sized lymphocytic cells in the bone marrow, consistent with the premortem diagnosis of WM/LPL. Additionally, immunoglobulin λ-light chain-derived amyloid (ALλ) deposition was identified in all organs other than the brain. Although ALλ deposition and LPL infiltration were found in the heart, they were not severe enough to cause severe functional impairment. Severe congestion and/or edema were observed in the lungs, liver, and brain. Although significant inflammatory cell infiltration was not found in any organs, laboratory tests revealed elevated serum levels of inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α and the presence of IgM-λ monoclonal protein.
CONCLUSION
Acute IRRs associated with the initial rituximab infusion were the major contributing factor to his sudden unexpected death. The autopsy findings of present case suggest the necessity for thorough monitoring of older patients with WM/LPL undergoing rituximab treatment, particularly when pronounced IRRs occur during the first administration, in addition to investigating complications of WM/LPL before infusion.
Topics: Humans; Waldenstrom Macroglobulinemia; Rituximab; Male; Aged, 80 and over; Autopsy; Death, Sudden; Antineoplastic Agents, Immunological; Bone Marrow; Fatal Outcome; Infusions, Intravenous
PubMed: 38943126
DOI: 10.1186/s13000-024-01519-9 -
Journal of Translational Medicine Jun 2024This study aims to elucidate the functional role of IQGAP1 phosphorylation modification mediated by the SOX4/MAPK1 regulatory axis in developing pancreatic cancer...
OBJECTIVE
This study aims to elucidate the functional role of IQGAP1 phosphorylation modification mediated by the SOX4/MAPK1 regulatory axis in developing pancreatic cancer through phosphoproteomics analysis.
METHODS
Proteomics and phosphoproteomics data of pancreatic cancer were obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Differential analysis, kinase-substrate enrichment analysis (KSEA), and independent prognosis analysis were performed on these datasets. Subtype analysis of pancreatic cancer patients was conducted based on the expression of prognostic-related proteins, and the prognosis of different subtypes was evaluated through prognosis analysis. Differential analysis of proteins in different subtypes was performed to identify differential proteins in the high-risk subtype. Clinical correlation analysis was conducted based on the expression of prognostic-related proteins, pancreatic cancer typing results, and clinical characteristics in the pancreatic cancer proteomics dataset. Functional pathway enrichment analysis was performed using GSEA/GO/KEGG, and most module proteins correlated with pancreatic cancer were selected using WGCNA analysis. In cell experiments, pancreatic cancer cells were grouped, and the expression levels of SOX4, MAPK1, and the phosphorylation level of IQGAP1 were detected by RT-qPCR and Western blot experiments. The effect of SOX4 on MAPK1 promoter transcriptional activity was assessed using a dual-luciferase assay, and the enrichment of SOX4 on the MAPK1 promoter was examined using a ChIP assay. The proliferation, migration, and invasion functions of grouped pancreatic cancer cells were assessed using CCK-8, colony formation, and Transwell assays. In animal experiments, the impact of SOX4 on tumor growth and metastasis through the regulation of MAPK1-IQGAP1 phosphorylation modification was studied by constructing subcutaneous and orthotopic pancreatic cancer xenograft models, as well as a liver metastasis model in nude mice.
RESULTS
Phosphoproteomics and proteomics data analysis revealed that the kinase MAPK1 may play an important role in pancreatic cancer progression by promoting IQGAP1 phosphorylation modification. Proteomics analysis classified pancreatic cancer patients into two subtypes, C1 and C2, where the high-risk C2 subtype was associated with poor prognosis, malignant tumor typing, and enriched tumor-related pathways. SOX4 may promote the occurrence of the high-risk C2 subtype of pancreatic cancer by regulating MAPK1-IQGAP1 phosphorylation modification. In vitro cell experiments confirmed that SOX4 promoted IQGAP1 phosphorylation modification by activating MAPK1 transcription while silencing SOX4 inhibited the proliferation, migration, and invasion of pancreatic cancer cells by reducing the phosphorylation level of MAPK1-IQGAP1. In vivo, animal experiments further confirmed that silencing SOX4 suppressed the growth and metastasis of pancreatic cancer by reducing the phosphorylation level of MAPK1-IQGAP1.
CONCLUSION
The findings of this study suggest that SOX4 promotes the phosphorylation modification of IQGAP1 by activating MAPK1 transcription, thereby facilitating the growth and metastasis of pancreatic cancer.
Topics: ras GTPase-Activating Proteins; Pancreatic Neoplasms; Humans; Proteomics; Phosphorylation; Disease Progression; SOXC Transcription Factors; Cell Line, Tumor; Animals; Mitogen-Activated Protein Kinase 1; Mice, Nude; Gene Expression Regulation, Neoplastic; Cell Proliferation; Prognosis; Mice; Male; Female; Phosphoproteins; Signal Transduction; Cell Movement
PubMed: 38943117
DOI: 10.1186/s12967-024-05377-3 -
BMC Public Health Jun 2024Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate...
BACKGROUND
Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa.
METHODS
From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up.
RESULTS
190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45-172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09-92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66-43.34], p = 0.010) were significantly related.
CONCLUSIONS
Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful.
Topics: Humans; Male; Prostatic Neoplasms; Aged; Republic of Korea; Middle Aged; Emotions; Biopsy; Surveys and Questionnaires; Decision Making; Cohort Studies; Prostate
PubMed: 38943112
DOI: 10.1186/s12889-024-19179-1 -
BMC Urology Jun 2024To evaluate the predictive value of individual components of the R.E.N.A.L scoring system for Laparoscopic (LPN) and Robotic Partial Nephrectomy (RPN).
BACKGROUND
To evaluate the predictive value of individual components of the R.E.N.A.L scoring system for Laparoscopic (LPN) and Robotic Partial Nephrectomy (RPN).
METHODS
Patients that had undergone a Laparoscopic (LPN) or Robotic Partial Nephrectomy (RPN) between 2018 and 2023 were reviewed. Our data collection included Race, Ethnicity, Age, BMI, R.E.N.A.L nephrometry score, and complications. Cases that achieved trifecta outcomes were designated as "Group A" and cases that did not achieve trifecta were "Group B". All the data were collected using REDCap database.
RESULTS
A total of 111 cases were included, Group A consisted of 82% of all cases, whereas Group B 18%. Radius score demonstrated significant distinction concerning trifecta attainment and was the most predictive component of the 5 scoring metrics of the nephrometry system. In a subgroup analysis, R-score of 3 or a renal mass measuring ≥ 7 cm, was a significant independent negative predictor for trifecta outcomes, as well as tumor size at presentation.
CONCLUSION
Renal nephrometry score is predictive of trifecta outcomes for patients undergoing laparoscopic or robotic partial nephrectomy. Radius of mass was the most effective predictive component of the nephrometry score for trifecta prediction.
Topics: Humans; Robotic Surgical Procedures; Nephrectomy; Laparoscopy; Male; Female; Middle Aged; Kidney Neoplasms; Treatment Outcome; Aged; Retrospective Studies; Predictive Value of Tests
PubMed: 38943111
DOI: 10.1186/s12894-024-01518-4