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Theranostics 2024Synergic reprogramming of metabolic dominates neuroblastoma (NB) progression. It is of great clinical implications to develop an individualized risk prognostication...
Synergic reprogramming of metabolic dominates neuroblastoma (NB) progression. It is of great clinical implications to develop an individualized risk prognostication approach with stratification-guided therapeutic options for NB based on elucidating molecular mechanisms of metabolic reprogramming. With a machine learning-based multi-step program, the synergic mechanisms of metabolic reprogramming-driven malignant progression of NB were elucidated at single-cell and metabolite flux dimensions. Subsequently, a promising metabolic reprogramming-associated prognostic signature (MPS) and individualized therapeutic approaches based on MPS-stratification were developed and further validated independently using pre-clinical models. MPS-identified MPS-I NB showed significantly higher activity of metabolic reprogramming than MPS-II counterparts. MPS demonstrated improved accuracy compared to current clinical characteristics [AUC: 0.915 vs. 0.657 (), 0.713 (INSS-stage), and 0.808 (INRG-stratification)] in predicting prognosis. AZD7762 and etoposide were identified as potent therapeutics against MPS-I and II NB, respectively. Subsequent biological tests revealed AZD7762 substantially inhibited growth, migration, and invasion of MPS-I NB cells, more effectively than that of MPS-II cells. Conversely, etoposide had better therapeutic effects on MPS-II NB cells. More encouragingly, AZD7762 and etoposide significantly inhibited in-vivo subcutaneous tumorigenesis, proliferation, and pulmonary metastasis in MPS-I and MPS-II samples, respectively; thereby prolonging survival of tumor-bearing mice. Mechanistically, AZD7762 and etoposide-induced apoptosis of the MPS-I and MPS-II cells, respectively, through mitochondria-dependent pathways; and MPS-I NB resisted etoposide-induced apoptosis by addiction of glutamate metabolism and acetyl coenzyme A. MPS-I NB progression was fueled by multiple metabolic reprogramming-driven factors including multidrug resistance, immunosuppressive and tumor-promoting inflammatory microenvironments. Immunologically, MPS-I NB suppressed immune cells via and signaling pathways. Metabolically, the malignant proliferation of MPS-I NB cells was remarkably supported by reprogrammed glutamate metabolism, tricarboxylic acid cycle, urea cycle, etc. Furthermore, MPS-I NB cells manifested a distinct tumor-promoting developmental lineage and self-communication patterns, as evidenced by enhanced oncogenic signaling pathways activated with development and self-communications. This study provides deep insights into the molecular mechanisms underlying metabolic reprogramming-mediated malignant progression of NB. It also sheds light on developing targeted medications guided by the novel precise risk prognostication approaches, which could contribute to a significantly improved therapeutic strategy for NB.
PubMed: 38948053
DOI: 10.7150/thno.93962 -
Oncology Research 2024This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in triple-negative breast cancer (TNBC).
OBJECTIVE
This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in triple-negative breast cancer (TNBC).
METHODS
ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR. ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis. The migration, invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.
RESULTS
ROR2 expression was high in metastatic TNBC tissues. ROR2 knockdown suppressed the migration, invasion and chemoresistance of TNBC cells. ROR2 overexpression in MDA-MB-435 cells promoted the migration, invasion, and chemoresistance. Moreover, ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin. ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.
CONCLUSION
ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.
PubMed: 38948021
DOI: 10.32604/or.2024.045433 -
World Journal of Transplantation Jun 2024Mesenchymal stem cells (MSCs) have tantalized regenerative medicine with their therapeutic potential, yet a cloud of controversies looms over their clinical... (Review)
Review
Mesenchymal stem cells (MSCs) have tantalized regenerative medicine with their therapeutic potential, yet a cloud of controversies looms over their clinical transplantation. This comprehensive review navigates the intricate landscape of MSC controversies, drawing upon 15 years of clinical experience and research. We delve into the fundamental properties of MSCs, exploring their unique immunomodulatory capabilities and surface markers. The heart of our inquiry lies in the controversial applications of MSC transplantation, including the perennial debate between autologous and allogeneic sources, concerns about efficacy, and lingering safety apprehensions. Moreover, we unravel the enigmatic mechanisms surrounding MSC transplantation, such as homing, integration, and the delicate balance between differentiation and paracrine effects. We also assess the current status of clinical trials and the ever-evolving regulatory landscape. As we peer into the future, we examine emerging trends, envisioning personalized medicine and innovative delivery methods. Our review provides a balanced and informed perspective on the controversies, offering readers a clear understanding of the complexities, challenges, and potential solutions in MSC transplantation.
PubMed: 38947963
DOI: 10.5500/wjt.v14.i2.90554 -
Frontiers in Oncology 2024This study aims to develop an artificial intelligence model utilizing clinical blood markers, ultrasound data, and breast biopsy pathological information to predict the...
OBJECTIVE
This study aims to develop an artificial intelligence model utilizing clinical blood markers, ultrasound data, and breast biopsy pathological information to predict the distant metastasis in breast cancer patients.
METHODS
Data from two medical centers were utilized, Clinical blood markers, ultrasound data, and breast biopsy pathological information were separately extracted and selected. Feature dimensionality reduction was performed using Spearman correlation and LASSO regression. Predictive models were constructed using LR and LightGBM machine learning algorithms and validated on internal and external validation sets. Feature correlation analysis was conducted for both models.
RESULTS
The LR model achieved AUC values of 0.892, 0.816, and 0.817 for the training, internal validation, and external validation cohorts, respectively. The LightGBM model achieved AUC values of 0.971, 0.861, and 0.890 for the same cohorts, respectively. Clinical decision curve analysis showed a superior net benefit of the LightGBM model over the LR model in predicting distant metastasis in breast cancer. Key features identified included creatine kinase isoenzyme (CK-MB) and alpha-hydroxybutyrate dehydrogenase.
CONCLUSION
This study developed an artificial intelligence model using clinical blood markers, ultrasound data, and pathological information to identify distant metastasis in breast cancer patients. The LightGBM model demonstrated superior predictive accuracy and clinical applicability, suggesting it as a promising tool for early diagnosis of distant metastasis in breast cancer.
PubMed: 38947897
DOI: 10.3389/fonc.2024.1409273 -
Frontiers in Oncology 2024To explore the value of F-fluordeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with...
OBJECTIVE
To explore the value of F-fluordeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II).
MATERIALS AND METHODS
A total of 65 patients with stage I-II cervical cancer underwent F-FDG PET/CT were included in our study. Comparing the primary tumor F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM.
RESULTS
There were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all <0.01). Logistic regression analysis showed that TLG was an independent predictor of LNM in stage I-II cervical cancer (OR 1.032, 95% CI 1.013-1.052, <0.01). Moreover, the predictive value of TLG combined with SUVpeak and SCC-Ag increased and the area under the curve increased compared SUVpeak and SCC-Ag.
CONCLUSION
F-FDG PET/CT semi-quantitative parameters and SCC-Ag have promise for assessing LNM in stage I-II cervical cancer. TLG of primary tumor provides independent and increasing values in predicting LNM in stage I-II cervical cancer.
PubMed: 38947896
DOI: 10.3389/fonc.2024.1278464 -
Journal of Surgical Case Reports Jun 2024During breast cancer recurrence, drug therapy is planned based on the biological characteristics of the primary tumor. However, the mechanisms underlying these changes...
During breast cancer recurrence, drug therapy is planned based on the biological characteristics of the primary tumor. However, the mechanisms underlying these changes have not yet been clarified. A 59-year-old woman underwent breast cancer surgery 23 years previously and received postoperative hormone therapy for 2 years. She had abdominal distention and ascites effusion and was diagnosed with carcinomatous peritonitis due to luminal-type breast cancer after ascites puncture. She received up to the fourth line of treatment. Subsequently, pleural effusion was observed and human epidermal growth factor receptor 2 type breast cancer was diagnosed because of pleurodesis. This case suggests that the cell block diagnostic method based on thoracic and ascites fluid cytology is useful not only for confirming the primary tumor but also for diagnosing the biological characteristics of breast cancer. In the treatment of breast cancer recurrence, it is important to plan the treatment, including aggressive re-biopsy of metastases.
PubMed: 38947869
DOI: 10.1093/jscr/rjae432 -
Endoscopic Ultrasound 2024Endobronchial ultrasound (EBUS) imaging is a valuable tool for predicting lymph node (LN) metastasis in lung cancer patients. This study aimed to develop a risk-scoring...
BACKGROUND AND OBJECTIVES
Endobronchial ultrasound (EBUS) imaging is a valuable tool for predicting lymph node (LN) metastasis in lung cancer patients. This study aimed to develop a risk-scoring model based on EBUS multimodal imaging (grayscale, Doppler mode, elastography) to predict LN metastasis in lung cancer patients.
PATIENTS AND METHODS
This retrospective study analyzed 350 metastatic LNs in 314 patients with lung cancer and 124 reactive LNs in 96 patients with nonspecific inflammation. The sonographic findings were compared with the final pathology results and clinical follow-up. Univariate and multivariate logistic regression analyses were performed to evaluate the independent risk factors of metastatic LNs. According to the coefficients of corresponding indicators in logistic regression analysis, a risk-scoring model was established. Receiver operating characteristic curve was applied to evaluate the predictive capability of model.
RESULTS
Multivariate analysis showed that short axis >10 mm, distinct margin, absence of central hilar structure, presence of necrosis, nonhilar vascularity, and elastography score 4 to 5 were independent predictors of metastatic LNs. Both short axis and margin were scored 1 point, and the rest of independent predictors were scored 2 points. The combination of 3 EBUS modes had the highest area under the receiver operating characteristic and accuracy of 0.884 (95% confidence interval, 0.846-0.922) and 87.55%, respectively. The risk stratification was as follows: 0 to 2 points, malignancy rate of 11.11%, low suspicion; 3 to 10 points, malignancy rate of 86.77%, high suspicion.
CONCLUSIONS
The risk-scoring model based on EBUS multimodal imaging can effectively evaluate metastatic LNs in lung cancer patients to support clinical decision making.
PubMed: 38947743
DOI: 10.1097/eus.0000000000000051 -
Cureus May 2024Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma (MFH), constitutes a significant subset of soft-tissue sarcomas. Despite its...
Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma (MFH), constitutes a significant subset of soft-tissue sarcomas. Despite its rarity, UPS poses substantial clinical challenges due to its aggressive behavior and propensity for distant metastasis. Here, we report a rare case of high-grade UPS located in the colon, a site exceptionally uncommon for this malignancy, in a 49-year-old woman. The case also underscores the importance of considering UPS in the differential diagnosis of colonic neoplasms. Understanding the clinical and pathological features of UPS in unusual locations like the large intestine is crucial for timely diagnosis and appropriate management strategies.
PubMed: 38947723
DOI: 10.7759/cureus.61346 -
Cureus May 2024Gastric cancer is the fifth leading cause of cancer-related deaths in the world. The occurrence of bone metastases (BM) in gastric cancer without prior gastrointestinal...
Gastric cancer is the fifth leading cause of cancer-related deaths in the world. The occurrence of bone metastases (BM) in gastric cancer without prior gastrointestinal (GI) symptoms is a rare phenomenon that has been sporadically documented in the existing literature. We report a case of a 27-year-old male presenting with chief complaints of severe backache for one month. After an upper gastrointestinal endoscopy and biopsy, the primary source of cancer was identified as a solitary gastric adenocarcinoma, supporting the diagnosis of bony metastases on the magnetic resonance imaging (MRI) of the spine. The patient was planned to start on palliative chemotherapy (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel {FLOT} regimen) with palliative radiotherapy of 20 Gy in five fractions to bony metastasis. The patient denied treatment and was discharged against medical advice.
PubMed: 38947693
DOI: 10.7759/cureus.61421 -
Cureus May 2024Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described rare and aggressive malignancy characterized by undifferentiated cell morphology...
Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described rare and aggressive malignancy characterized by undifferentiated cell morphology and the loss of the Brahma-related gene 1 (BRG1) protein. Its pathogenesis involves mutational loss of SMARCA4 gene expression, which encodes the BRG1 protein that serves as one of the catalytic subunits of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. This malignancy of the thorax predominantly affects middle-aged male smokers and commonly metastasizes to lymph nodes, bones, adrenal glands, liver, gastrointestinal tract, central nervous system, and kidney. Cases of brain metastasis have been reported but are less common. We report a case of this tumor initially presenting with diffuse brain metastasis in a 55-year-old male with a significant smoking history. We reviewed the current literature on the diagnostic and therapeutic challenges posed by this highly aggressive thoracic tumor.
PubMed: 38947666
DOI: 10.7759/cureus.61367