Neoplasma[JOURNAL]
Sun
200 papers
Predicting the efficacy of immune checkpoint inhibitors monotherapy in advanced non-small cell lung cancer: a machine learning method based on multidimensional data.
Liu N, Liang BL, Lu L … +6 more , Zhang BQ, Sun JJ, Yang JT, Xu J, Song ZB, Shi L
Neoplasma · 2023 Apr · PMID 36812231 · Publisher ↗
Immunotherapy has improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC), but only a small subset of patients achieved clinical benefit. The purpose of our study was to integrate multidimensi...
Immunotherapy has improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC), but only a small subset of patients achieved clinical benefit. The purpose of our study was to integrate multidimensional data using a machine learning method to predict the therapeutic efficacy of immune checkpoint inhibitors (ICIs) monotherapy in patients with advanced NSCLC. We retrospectively enrolled 112 patients with stage IIIB-IV NSCLC receiving ICIs monotherapy. The random forest (RF) algorithm was used to establish efficacy prediction models based on five different input datasets, including precontrast computed tomography (CT) radiomic data, postcontrast CT radiomic data, a combination of the two CT radiomic data, clinical data, and a combination of radiomic and clinical data. The 5-fold cross-validation was used to train and test the random forest classifier. The performance of the models was assessed according to the area under the curve (AUC) in the receiver operating characteristic curve. Survival analysis was performed to determine the difference in progression-free survival (PFS) between the two groups with the prediction label generated by the combined model. The radiomic model based on the combination of precontrast and postcontrast CT radiomic features and the clinical model produced an AUC of 0.92±0.04 and 0.89±0.03, respectively. By integrating radiomic and clinical features together, the combined model had the best performance with an AUC of 0.94±0.02. The survival analysis showed that the two groups had significantly different PFS times (p<0.0001). The baseline multidimensional data including CT radiomic and multiple clinical features were valuable in predicting the efficacy of ICIs monotherapy in patients with advanced NSCLC.
Allogeneic stem cell transplantation in patients with multiple myeloma-single center experience.
Kříž T, Jungová A, Lysák D … +4 more , Karas M, Hrabětová M, Šrámek J, Jindra P
Neoplasma · 2023 Apr · PMID 36812230 · Publisher ↗
The standard of care in multiple myeloma (MM) consists of induction chemotherapy followed by autologous stem cell transplant (autoSCT), but this setting doesn't present curative potential. Despite advances in new, effici...
The standard of care in multiple myeloma (MM) consists of induction chemotherapy followed by autologous stem cell transplant (autoSCT), but this setting doesn't present curative potential. Despite advances in new, efficient, and targeted drugs, allogeneic transplant (aloSCT) remains the modality with curative potential in MM. With the knowledge of high mortality and morbidity related to the treatment in comparison to treatment with novel drugs, there is no consensus in the indication of aloSCT in MM, also the choice of ideal patients profiting from this method is difficult. Therefore, we performed a retrospective unicentric study of 36 unselected consecutive patients transplanted for MM in the University Hospital in Pilsen between the years 2000-2020 in order to define possible variables influencing survival. The median age of the patients was 52 years (38-63) and the distribution of MM subtypes was standard. The majority of the patients were transplanted in the relapse setting, 3 (8.3%) patients in the 1st line setting, and in 7 (19%) patients elective auto-alo tandem transplant was performed. 18 patients (60% of patients with available cytogenetics (CG) had high-risk disease. 12 (33.3%) patients were transplanted with chemoresistant disease (at least PR not reached). With a median follow-up of 85 months, we observed median overall survival (OS) of 30 months (range 10-60) and median progression-free survival (PFS) of 15 months (11-175). 1- and 5-year Kaplan Meier survival probabilities for OS were 55% and 30.5% respectively. During the follow-up, 27 (75%) patients died, 11 (35%) due to treatment-related mortality (TRM), and 16 patients (44%) due to a relapse. 9 (25%) patients were still alive, 3 (8.3%) of them with complete remission (CR), and 6 (16.7%) patients with relapse/progression. Altogether 21 (58%) of the patients relapsed/progressed with a median of 11 months (3-175). Incidence of clinically significant acute graft versus host disease (aGvHD gr. >II) was low (8.3%) and extensive chronic GvHD (cGvHD) developed in 4 patients (11.1%). Univariant analysis proved marginal statistical significance in disease status before aloSCT (chemosensitive × chemoresistant) for OS, favoring patients with the chemosensitive disease (HR 0.43, 95% CI 0.18-1.01, p=0.05), there was no significant impact of high-risk cytogenetics (CG) on survival. No other analyzed parameter was found to be significant. Our findings support the conclusion that aloSCT is able to overcome high-risk CG and that aloSCT still remains a valid treatment choice with acceptable toxicity in well-selected high-risk patients with curative potential, even though often with active disease, but not derogating the quality of life significantly.
Challenges of in situ hybridization in miRNA analysis of triple-negative breast cancer morphological diversity.
Kolečková M, Bezděková M, Bouchal J … +8 more , Janíková M, Bohošová J, Slabý O, Svoboda M, Srovnal J, Vomáčková K, Überall I, Kolář Z
Neoplasma · 2023 Apr · PMID 36812229 · Publisher ↗
miRNA expression in triple-negative breast cancers (TNBC) has mainly been studied from a methodological viewpoint. However, it has not been considered that miRNA expression profile may be associated with a specific morph...
miRNA expression in triple-negative breast cancers (TNBC) has mainly been studied from a methodological viewpoint. However, it has not been considered that miRNA expression profile may be associated with a specific morphological entity inside every tumor. The verification of this hypothesis on a set of 25 TNBCs was the subject of our previous work, where we confirmed specific expression of the studied miRNAs in 82 samples of different morphologies including inflammatory infiltrate, spindle cell, clear cell, and metastases after RNA extraction and purification as well as microchip and biostatistical analysis. In the current work, we demonstrate a low suitability of in situ hybridization method for miRNA detection compared to RT-qPCR, and in detail discuss the biological role of 8 miRNAs with the most significant changes of expression.
LINC00504 promotes the progression of acute myeloid leukemia by targeting MDM2.
Yan JH, Yao L, Tan Y … +1 more , Wang Y
Neoplasma · 2023 Apr · PMID 36812228 · Publisher ↗
Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignant tumor, accompanied by the abnormal cloning of myeloid hematopoietic stem cells, little is known about its etiological role and pathogenesis....
Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignant tumor, accompanied by the abnormal cloning of myeloid hematopoietic stem cells, little is known about its etiological role and pathogenesis. We aimed to explore the effect and regulatory mechanism of LINC00504 on the malignant phenotypes of AML cells. In this study, LINC00504 levels in AML tissues or cells were ascertained by PCR. RNA pull-down and RIP assays were conducted to verify the combination of LINC00504 and MDM2. Cell proliferation was detected by CCK-8 and BrdU assays, apoptosis was checked by flow cytometry, and glycolytic metabolism levels were detected by ELISA analysis. The expressions of MDM2, Ki-67, HK2, cleaved caspase-3, and p53 were detected by western blotting and immunohistochemistry. A xenograft tumor model was used to detect the role of LINC00504 in vivo. Results showed that LINC00504 was highly expressed in AML and its high expression was related to clinicopathological features in AML patients. LINC00504 knockdown significantly inhibited the proliferation and glycolysis, while inducing apoptosis of AML cells. Meanwhile, LINC00504 downregulation also exerted a significant alleviating effect on AML cell growth in vivo. In addition, LINC00504 could bind to MDM2 protein and positively regulate its expression. Overexpression of LINC00504 promoted the malignant phenotypes of AML cells and partially reversed the inhibitory effects of LINC00504 knockdown on AML progression. In conclusion, LINC00504 facilitated AML cell proliferation and suppressed apoptosis through upregulating MDM2 expression, suggesting that LINC00504 may serve as a prognostic marker and therapeutic target in patients with AML.
BDNF, sHLA-G, and sTREM-1 are useful blood biomarkers for identifying grade IV glioma patients.
Kluckova K, Kozak J, Svajdler M … +5 more , Steno J, Matejcik V, Durmanova V, Zsemlye E, Bucova M
Neoplasma · 2023 Feb · PMID 36704922 · Publisher ↗
Inflammation and immunity belong to the main factors influencing tumor growth. In this study, we attempted to identify a profile of biomarkers associated with gliomas. We found decreased serum levels of sTREM-1 (soluble...
Inflammation and immunity belong to the main factors influencing tumor growth. In this study, we attempted to identify a profile of biomarkers associated with gliomas. We found decreased serum levels of sTREM-1 (soluble triggering receptor expressed on myelocytes) and increased levels of IL-10 in all grades of glioma patients in comparison with healthy controls (sTREM-1: grade II: p=0.0051, grade III: p=0.02, grade IV: p=0.01; IL-10: grade II: p=0.0017, grade III: p=0.03, grade IV: p=0.007). However, we did not find any combination of tested markers with good sensitivity and specificity in grades II and III of glioma patients to discriminate them from healthy controls. In grade IV glioma patients, two sets of markers showed promising results in distinguishing patients from healthy people. For the first set consisting of four selected markers, sTREM-1, sHLA-G, BDNF, and IL-13, the ROC curves indicate a good discriminatory capability for glioblastoma patients (AUC=0.9510). The best discriminatory capability for glioblastoma patients (AUC=0.9534) was found for the second set consisting of three selected markers sTREM-1, sHLA-G, and BDNF with 79.2% sensitivity and 94.1% specificity.
Cryptotanshinone inhibits oral squamous cell carcinoma through the autophagic pathway.
Jiang XT, Qiu Y, Li CH
Neoplasma · 2023 Feb · PMID 36704921 · Publisher ↗
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients...
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients, it is urgent to find new and efficient drugs with good safety for clinical treatment. This study aimed to identify potential anticancer drugs starting from the traditional Chinese medicine Salvia miltiorrhiza extract. Cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, was found to significantly induce apoptosis and inhibit proliferation in OSCC. By electron microscopy, autophagosomes were found. Confocal fluorescence microscopy data showed that cryptotanshinone significantly induced autophagy in OSCC cells. Mechanistically, the western blot assay indicated that cryptotanshinone induced cell autophagy through the activation of the LC3 pathway, whereas the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, we demonstrated that cryptotanshinone had a significant antitumor effect in a tumor xenograft model, and no damage to vital organs was observed. Our findings provide evidence that cryptotanshinone may be a novel therapeutic strategy for the treatment of OSCC.
HOXA5 inhibits the proliferation and metastasis of cervical squamous cell carcinoma by suppressing the β-catenin/Snail signaling.
Jin WY, Zhang Y, Tian J … +8 more , Xu LK, Lin HJ, Yang YZ, Zhang XM, Jin MH, Mo WF, Qi GY, Zhou YQ
Neoplasma · 2023 Feb · PMID 36660797 · Publisher ↗
HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explo...
HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explore the function of HOXA5 in CSCC and its molecular mechanism. Immunohistochemistry showed that HOXA5 expression was downregulated in human CSCC tissues and HOXA5 staining was negatively correlated with tumor size and histological grade of CSCC. Ectopic expression of HOXA5 inhibited proliferative and metastatic abilities of CSCC cells in vitro and in vivo. Furthermore, overexpression of HOXA5 inhibited the cell cycle by arresting the S/G2 phase by flow cytometry and that was related to the downregulation of Cyclin A. Further study showed that HOXA5 suppressed EMT by inhibiting the β-catenin/Snail signaling resulting in reduced metastasis of CSCC cells. Altogether, our results suggested that HOXA5 inhibited the proliferation and metastasis via repression of the β-catenin/Snail pathway, proposing the potential role of HOXA5 in the prevention and treatment of CSCC.
Semaphorin 3A inhibits tumor progression via the downregulation of Lin28B in ovarian cancer.
Ma RY, Yang LN, Chen JN … +3 more , Chen RJ, Zhang LW, Wang XQ
Neoplasma · 2023 Feb · PMID 36660796 · Publisher ↗
Semaphorin 3A (Sema3A) has recently been proven to play an essential role in tumorigenesis. Here, the role of Sema3A in ovarian cancer is explored. The prognostic value of Sema3A was evaluated using the Kaplan-Meier plot...
Semaphorin 3A (Sema3A) has recently been proven to play an essential role in tumorigenesis. Here, the role of Sema3A in ovarian cancer is explored. The prognostic value of Sema3A was evaluated using the Kaplan-Meier plotter database, and stable expression cells were established by the delivery of lentivirus harboring SEMA3A cDNA or shRNA into OVCA433 and SKOV3 cells, respectively. Then CCK-8 assay, colony-formation assay, wound-healing assay, and Transwell assay were utilized to verify the effect of Sema3A on tumorigenesis. Co-cultures of ovarian cancer cells (OVCA433 and SKOV3) with a conditional medium collected from the established cells were further utilized to confirm the function of Sema3A. Then, the RNA-seq assay was adopted to explore the underlying mechanism. The results demonstrated that low expression of Sema3A was predictive of poor overall survival in patients with ovarian cancer. Functional experiments revealed that Sema3A inhibited proliferation, migration, and invasion in ovarian cancer cells. Secreted Sema3A in a conditioned culture medium also exhibited an anti-tumor effect in ovarian cancer cells. RNA-seq assay suggested that focal adhesion and Lin28B were involved in regulating Sema3A. Rescue assays further verified that Lin28B/ROCK1 axis was vital in the regulation of Sema3A and Lin28B significantly upregulated ROCK1 through let-7g microRNA. The presented data indicate that Sema3A inhibits proliferation and metastasis via the downregulation of Lin28B/ROCK1 in ovarian cancer.
Triptonide inhibits growth and metastasis in HCC by suppressing EGFR/PI3K/AKT signaling.
Zhang H, Mao Y, Zou X … +6 more , Niu J, Jiang J, Chen X, Zhu M, Yang X, Dong T
Neoplasma · 2023 Feb · PMID 36637084 · Publisher ↗
Liver cancer represents one of the deadliest cancers, with a rising incidence worldwide. Triptonide is found in the traditional Chinese medicinal plant Tripterygium wilfordii Hook. This study aimed to examine the antican...
Liver cancer represents one of the deadliest cancers, with a rising incidence worldwide. Triptonide is found in the traditional Chinese medicinal plant Tripterygium wilfordii Hook. This study aimed to examine the anticancer properties of triptonide in human hepatocellular carcinoma (HCC). HCC cells were administered with triptonide at various levels, and CCK-8 and colony formation assays were carried out for detecting HCC cell proliferation. Then, cell apoptosis and cell cycle distribution were evaluated by flow cytometry. Tumor growth was monitored noninvasively by ultrasound imaging. Cell migration and invasion were quantitated by wound healing and Transwell assays. A metastasis model was established via tail vein injection of HCC cells in nude mice. Immunoblot was performed to quantitate the expression of proteins involved in the EGFR/PI3K/AKT signaling and its downstream effectors. Triptonide repressed cell proliferation and induced cell cycle arrest and apoptosis in cultured HCC cells, and suppressed tumor growth in vivo. In addition, triptonide inhibited EMT, migration and invasion in cultured HCC cells, and lung metastasis in nude mice. Mechanistically, triptonide acted by inhibiting the EGFR/PI3K/AKT signaling and regulated its downstream effectors, e.g., the cell cycle-associated protein cyclin D1, the apoptosis-related protein Bcl-2, the EMT marker E-cadherin, and the invasion-related protein MMP-9. Triptonide suppresses proliferation, EMT, migration and invasion, and promotes apoptosis and cell cycle arrest by repressing the EGFR/PI3K/AKT signaling. Therefore, triptonide might be considered for liver cancer treatment.
Zerumbone combined with gefitinib alleviates lung cancer cell growth through the AKT/STAT3/SLC7A11 axis.
Wang JG, Li DL, Fan R … +1 more , Yan MJ
Neoplasma · 2023 Feb · PMID 36637083 · Publisher ↗
Zerumbone had been verified as a potential anti-cancer agent. Our research aimed to investigate the effect of zerumbone combined with gefitinib in lung cancer. Human pulmonary alveolar epithelial cells (HPAEpiC), A549, a...
Zerumbone had been verified as a potential anti-cancer agent. Our research aimed to investigate the effect of zerumbone combined with gefitinib in lung cancer. Human pulmonary alveolar epithelial cells (HPAEpiC), A549, and H460 cell lines were used to detect the efficacy of zerumbone. BALB/c nude mice were randomly divided into five groups, including model, gefitinib (Gef, 10 mg/kg), low dose zerumbone (L-Zer, 20 mg/kg), high dose zerumbone (H-Zer, 40 mg/kg), and H-Zer + Gef groups, and the tumor growth in each group was monitored. TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect cell apoptosis. Immunohistochemistry (IHC), immunofluorescence, and western blot were used to analyze the protein expressions in tumor tissues. Glutathione (GSH) and malondialdehyde (MAD) were detected by special kits. Zerumbone inhibited the proliferation of lung cancer cells in vitro. Tumor volume and weight were reduced after gefitinib or zerumbone treatment. Gefitinib and zerumbone treatment significantly promoted the apoptosis of tumor cells. The expression of Bcl-2, Bax, and P53 proteins confirmed cell apoptosis. IHC results indicated that zerumbone and gefitinib treatment decreased tumor angiogenesis. Consistent with this result, the expression of EGFR, VEGFR2, and Ki-67 proteins decreased, while the expression of angiostatin and endostatin proteins increased. Interestingly, zerumbone treatment increased the level of MDA while decreasing GSH. Next, the levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) decreased after zerumbone and gefitinib treatment. Our study suggested that zerumbone combined with gefitinib could effectively inhibit lung cancer for multi-model therapies, including the inhibition of tumor growth, angiogenesis, induce cell apoptosis, and ferroptosis.
Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.
Almuradova E, Basoglu T, Nayir E … +28 more , Bayram E, Paydas S, Gokmen I, Karakaya S, Oksuzoglu B, Erdem D, Sakin A, Atcı M, Belen Gulbagcı B, Hacibekiroglu I, Onder AH, Karaarslan S, Karakurt Eryılmaz M, Korkmaz M, Yazıcı O, Sutcuoglu O, Akagunduz B, Arak H, Sakalar T, Aydin D, Iriagac Y, Alan O, Midik M, Cetin D, Kip AD, Turhal S, Kacan T, Koseci T
Neoplasma · 2023 Feb · PMID 36620878 · Publisher ↗
Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share o...
Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.
Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPK/YAP pathway.
Wang YL, Wang Q, Li H … +3 more , Wang CC, Ma YL, Han Z
Neoplasma · 2023 Feb · PMID 36620877 · Publisher ↗
Non-small cell lung cancer (NSCLC) is characterized by high incidence and mortality, severely threatening human health. The infinite growth and metastasis of NSCLC cells result in a poor prognosis. Therefore, our study w...
Non-small cell lung cancer (NSCLC) is characterized by high incidence and mortality, severely threatening human health. The infinite growth and metastasis of NSCLC cells result in a poor prognosis. Therefore, our study was to investigate the mechanism of Sestrin2 on the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Human embryonic lung fibroblasts, NSCLC cell lines, and nude mice were experimental subjects in this study. qRT-PCR and western blot were performed to evaluate the mRNA and protein expression of genes. CCK-8 and EdU assay were conducted to detect cell proliferation. The scratch test and Transwell assay were applied to examine cell migration and invasion. The bioinformatics analysis and Co-IP assay were employed to predict and consolidate the interaction between YAP and TEAD. We found the expression of Sestrin2 was declined but the expression of YAP was elevated in NSCLC cells. Sestrin2 sufficiency or YAP silencing could effectively impair cell growth and metastasis. Mechanistically, YAP interacted with TEAD to enhance FOXM1 expression. Additionally, the elevation of FOXM1 abolished the inhibitory influences of Sestrin2 sufficiency on NSCLC cell growth, invasion, and EMT process. Eventually, Sestrin2 elevation attenuated tumor growth in mice via modulation of the AMPK/YAP/FOXM1 axis, which was reversed by FOXM1 overexpression. Our consequences suggested Sestrin2 could inhibit the activation of YAP via prompting AMPK phosphorylation and then suppress FOXM1 expression through the interplay between YAP and TEAD to impair the capacities of NSCLC cell proliferation, migration, invasion, and EMT. This study provided a novel mechanism of Sestrin2 in NSCLC.
CBX3 promotes breast cancer progression and high level of CBX3 predicts poor prognosis in patients.
Yang K, Wang YL, Zhu Z … +7 more , Cao XH, Liang MX, Xu D, Fei YJ, Yang SY, Zhou HL, Tang JH
Neoplasma · 2023 Feb · PMID 36620876 · Publisher ↗
Breast cancer is one of the leading cancer deaths around the world. Targeted drugs have greatly increased the survival rate of breast cancer patients in recent years. But in some patients, the current regimen is still in...
Breast cancer is one of the leading cancer deaths around the world. Targeted drugs have greatly increased the survival rate of breast cancer patients in recent years. But in some patients, the current regimen is still ineffective. Therefore, more therapeutic targets for treating breast cancer are demanding. The core heterochromatin-related genes of breast cancer were identified by utilizing prognostic survival analysis and multivariate Cox hazard proportional regression analysis. Both breast cancer and adjacent normal tissue were collected and analyzed with western blot and immunohistochemistry. Colony formation assay, CCK-8 assay, and EdU assay were used to measure the effect of CBX3 on breast cancer cell growth, wound-healing assay and Transwell assay were used to analyze the effect of CBX3 on breast cancer cell migration and invasion. Flow cytometry assay and western blot were used to study the molecular mechanism of CBX3 in breast cancer. High expression of heterochromatin-related proteins CBX3, H2AFY, and SULF1 showed a poor prognosis in patients in both TCGA dataset and GEO datasets. Western blot demonstrated that the expression level of CBX3 was significantly higher in breast cancer than that in adjacent normal tissues. Colony formation assay, CCK-8 assay, and EdU assay showed that the knockdown of CBX3 could significantly inhibit breast cancer cell growth, and the overexpression of CBX3 could promote the growth of breast cancer cells. Transwell assay and wound healing assay showed that knockdown of CBX3 inhibited breast cancer cell migration and invasion, and the overexpression of CBX3 promoted breast cancer cell migration and invasion. Western blot showed that CBX3 might promote breast cancer cell proliferation, invasion, and migration in breast cancer by modulating the ERK1/2 signaling pathway and epithelial-mesenchymal transition (EMT)-related genes. CBX3 was a biomarker of poor prognosis in breast cancer patients. CBX3 promoted the proliferation of breast cancer cells through the ERK signaling pathway, and migration and invasion of breast cancer cells through EMT-related genes. The CBX3/p-ERK1/2 signaling axis might provide a new therapeutic method against breast cancer.
Identification and validation of circulating biomarkers for detection of liver cancer with antibody array.
Zhang S, Gao C, Zhou Q … +8 more , Chen L, Huang GF, Tang H, Song X, Zhang Z, Whittaker K, Chen X, Huang RP
Neoplasma · 2023 Feb · PMID 36620875 · Publisher ↗
The aim of this study was to find new protein biomarkers that could be used to detect hepatocellular carcinoma (HCC) in the serum. We identified 11 proteins in the tissue that could be used to classify samples from HCC a...
The aim of this study was to find new protein biomarkers that could be used to detect hepatocellular carcinoma (HCC) in the serum. We identified 11 proteins in the tissue that could be used to classify samples from HCC and control subjects. The 11 identified tissue biomarkers were combined with 10 commonly used serum HCC biomarkers for further verification in a large number of serum samples from HCC patients and healthy controls. 17 of the 21 prospective serum biomarkers were determined to be differentially expressed through collinearity and significance analysis. Through the method of supervised learning, a random forest model was constructed to reduce the dimensionality of the number of differentially expressed proteins, and finally, 4 differentially expressed proteins were identified: AFP, GDF15, CEACAM-1, and MMP-9, and suggested to have potential application in clinical diagnosis of HCC.
Burkitt lymphoma-a retrospective analysis of data from the Registry of the Czech Lymphoma Study Group with external validation of the Burkitt lymphoma International Prognostic Index.
Sýkorová A, Procházka V, Móciková H … +10 more , Janíková A, Pytlík R, Belada D, Benešová K, Klener P, Ďuraš J, Smolej L, Campr V, Blahovcová P, Trněný M
Neoplasma · 2022 Dec · PMID 36591807 · Publisher ↗
Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin's lymphoma with an aggressive course. To refine the individual patient's prognosis, the International Prognostic Index for BL (BL-IPI) was recently developed and 4 r...
Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin's lymphoma with an aggressive course. To refine the individual patient's prognosis, the International Prognostic Index for BL (BL-IPI) was recently developed and 4 risk factors (RF) were determined as optimal prognostic cut-off by multivariate analysis: age ≥40 years, lactate dehydrogenase >3× upper limit of normal, ECOG performance status ≥2, and central nervous system involvement. The BL-IPI distinguishes 3 prognostic groups, low (without RF), intermediate (1 RF), and high risk (2-4 RF), with significant differences in survival. The aim of the current project was to perform an external validation of the BL-IPI in 101 patients from the Registry of Czech Lymphoma Study Group diagnosed between 1999 and 2016 (median age, 45 years). The median follow-up was 50.4 months. The induction treatment included rituximab plus chemotherapy in 82% and chemotherapy alone in 18%. The overall response rate was 78% and the complete remission rate was 73%. According to BL-IPI, low/intermediate/high risk was present in 21/35/45% of patients, showing high similarity to the training BL-IPI US (United States) dataset (18/36/46%). There were significant differences in progression-free survival (PFS) and overall survival (OS) between patients with high vs. intermediate risk (PFS: hazard ratio 0.16, 95% confidence interval 0.08-0.31, p<0.0001; OS: hazard ratio 0.17, 95% confidence interval 0.09-0.35, p<0.0001) but not between patients with low vs. intermediate risk. The 3-year OS probability according to BL-IPI with low/intermediate/high risk was 96/76/59% in the BL-IPI training dataset vs. 95/85/45% in our external validation cohort; the 3-year PFS probability with low/intermediate/high risk was 92/72/53% in the BL-IPI training dataset vs. 95/85/42% in our cohort. In summary, our external validation of the BL-IPI confirmed a good separation of high-risk patients, who have a poor prognosis and for whom the new therapeutic approaches are needed; patients with low and intermediate risk had favorable clinical outcomes, and differences between these groups were not significant, likely due to a small number of patients.
Mast cells as a tumor microenvironment factor associated with the aggressiveness of prostate cancer.
Zadvornyi T, Lukianova N, Borikun T … +6 more , Tymoshenko A, Mushii O, Voronina O, Vitruk I, Stakhovskyi E, Chekhun V
Neoplasma · 2022 Dec · PMID 36591806 · Publisher ↗
We aimed to investigate the relationship between the degree of mast cells' (MCs) infiltration and clinicopathological features of prostate cancer (PCa) malignancy and to find out the possible mechanisms of the involvemen...
We aimed to investigate the relationship between the degree of mast cells' (MCs) infiltration and clinicopathological features of prostate cancer (PCa) malignancy and to find out the possible mechanisms of the involvement of these cells in the formation of the aggressive course of the PCa development. The study was conducted on the clinical material of 60 patients with PCa of stages II-III. MCs in the PCa tissue were determined by a histochemical method using toluidine blue. The expression of osteopontin (OPN) was studied by the immunohistochemical method. The expression of miRNA-21, -126, -146a, -181a, and -221 was investigated by quantitative real-time PCR. Statistical processing of the results was performed using the GraphPad Prism 8 program. Our results demonstrated that the increased level of infiltration and degranulation of MCs in the PCa tissue was associated with such indices of the malignancy of the tumor process as the Gleason score and the preoperative PSA level in the blood serum of patients. A high level of MCs infiltration of the PCa tissue was associated with a significant decrease in the two-year recurrence-free survival rates of the patients by 23.3% (р=0.0455). A high degree of MCs infiltration of the PCa tissue was associated with 1.2 times (p=0.0347) higher level of OPN expression and 1.7 (p=0.0051) and 1.65 (p=0.0087) times lower levels of miR-126 and miR-181a expression, respectively. The obtained results indicate the participation of MCs as a factor of the tumor microenvironment in the PCa progression.
Real-world evidence of efficacy and safety of pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: Czech registry data.
Sandecka V, Pour L, Špička I … +14 more , Minařík J, Radocha J, Jelínek T, Pavlíček P, Jungová A, Kessler P, Wróbel M, Štork M, Štraub J, Pika T, Čápková L, Ševčíková S, Maisnar V, Hájek R
Neoplasma · 2022 Dec · PMID 36591805 · Publisher ↗
We assessed the outcomes of pomalidomide and dexamethasone treatment in relapsed/refractory multiple myeloma (RRMM) patients with ≥1 prior line of therapy. We analyzed the data of all RRMM patients treated with pomalidom...
We assessed the outcomes of pomalidomide and dexamethasone treatment in relapsed/refractory multiple myeloma (RRMM) patients with ≥1 prior line of therapy. We analyzed the data of all RRMM patients treated with pomalidomide and dexamethasone at nine Czech centers between 2013 and 2018. The source of the data was the Registry of Monoclonal Gammopathies of the Czech Republic. Primary endpoints included response rates based on International Myeloma Working Group criteria and survival measures, including progression-free survival (PFS) and overall survival (OS). Secondary endpoints were toxicities and previous treatment patterns, including refractory to lenalidomide, and their impact on final outcomes. The overall response rate was 51.8% and the clinical benefit rate (including patients with minimal response) was 67.1%, with 0.6% of complete responses, 8.5% of very good partial responses, and 42.1% of partial responses (PR). Overall, 16.5% of patients had a minimal response, and 32.3% had stable disease /progression. Median PFS was 8.8 months and the median OS was 14.2 months. In patients who achieved ≥PR, the median PFS and OS were significantly longer compared to non-responders (median PFS (12.1 vs. 4.5 months, p≤0.001 respectively), median OS (22.1 vs. 7.7 months, p≤0.001, respectively). The most frequent adverse events (AEs) were neutropenia (29.9%) and anemia (18.9%), non-hematological AEs included infections (14.6%) and fatigue (7.3%). Our analysis confirmed the effectiveness of pomalidomide and dexamethasone in a real-world setting. This therapy achieved reasonable outcomes comparable to the data from clinical trials even though this was an unbiased cohort of patients.
LncRNA CBR3-AS1 predicts a poor prognosis and promotes cervical cancer progression through the miR-3163/LASP1 pathway.
Cai Y, Huang Y, Zhang J … +7 more , Liu X, Zhao F, Zhang K, Xu S, Yang Y, Huang H, Gao Y
Neoplasma · 2022 Dec · PMID 36591804 · Publisher ↗
LncRNA carbonyl reductase antisense RNA 1 (CBR3-AS1) is increased in cervical cancer and predicts poor prognosis. This study aims to investigate the underlying mechanism of lncRNA CBR3-AS1 in cervical cancer. LncRNA CBR3...
LncRNA carbonyl reductase antisense RNA 1 (CBR3-AS1) is increased in cervical cancer and predicts poor prognosis. This study aims to investigate the underlying mechanism of lncRNA CBR3-AS1 in cervical cancer. LncRNA CBR3-AS1 and LASP1 expressions were significantly elevated in cervical cancer tissue and cells, whereas miR-3163 expression was significantly decreased in cervical cancer tissue and cells. High lncRNA CBR3-AS1 expression and LASP1 expression showed a lower overall survival rate, whereas high miR-3163 expression showed a higher overall survival rate. Correlation between clinicopathological parameters of cervical cancer patients and lncRNA CBR3-AS1, miR-3163, LASP1 expressions indicated that the expressions of lncRNA CBR3-AS1, miR-3163, and LASP1 were closely related with distant metastasis and lymphatic metastasis of cervical cancer. LncRNA CBR3-AS1 knockdown suppressed cervical cancer cell viability and inhibited cancer stem cell-like properties. Besides, we identified that lncRNA CBR3-AS1 interacted with miR-3163, and miR-3163 targeted to LASP1. Moreover, the correlation between lncRNA CBR3-AS1 and miR-3163, as well as the correlation between miR-3163 and LASP1 was confirmed. Finally, lncRNA CBR3-AS1 knockdown inhibited tumor growth and suppressed cancer stem cell-like properties of cervical cancer in vivo. Taken together, high expression of lncRNA CBR3-AS1 predicts poor prognosis in cervical cancer, and the lncRNA CBR3-AS1/miR-3163/LASP1 pathway plays a vital function in the modulation of cervical cancer cell proliferation and cancer stem cell-like properties.
Stanniocalcin1 knockdown induces ferroptosis and suppresses glycolysis in prostate cancer via the Nrf2 pathway.
Dai YQ, Bai Y, Gu J … +1 more , Fan BY
Neoplasma · 2022 Dec · PMID 36591803 · Publisher ↗
Stanniocalcin1 (STC1) is a secreted glycoprotein, which is highly expressed in prostate cancer cells. However, the biological functions of STC1 in modulating ferroptosis and glycolysis in prostate cancer are still not cl...
Stanniocalcin1 (STC1) is a secreted glycoprotein, which is highly expressed in prostate cancer cells. However, the biological functions of STC1 in modulating ferroptosis and glycolysis in prostate cancer are still not clear. The viability of PC-3 and DU145 cells was detected by CCK-8 assay. The relative Fe2+ level was detected by an Iron Assay Kit. MDA level was detected by Lipid Peroxidation MDA Assay Kit. Glucose uptake and lactate product were measured by Glycolysis Assay Kit and Lactate Assay Kit. In this study, STC1 was highly expressed in prostate cancer tissue specimens and cells. STC1 knockdown suppressed prostate cancer cell proliferation, and upregulated Fe2+ level, reduced glutathione (GSH) level, downregulated GPX4 and SLC7A11 protein expressions in PC-3 cells and DU145 cells. Besides, STC1 knockdown decreased glucose uptake, lactate product, and ATP level, as well as downregulated glycolysis-related protein HK2 and LDHA protein expressions. In addition, STC1 knockdown repressed the Nrf2/HO-1/NQO1 pathway. Nrf2 pathway activator, Oltipraz, upregulated Nrf2, total NQO1, and HO-1 expressions in PC-3 cells and DU145 cells. Moreover, Nrf2 pathway activator Oltipraz reversed the effect of STC1 knockdown on Fe2+ level and GPX4, SLC7A11, HK2, LDHA protein expressions in PC-3 cells and DU145 cells. Finally, STC1 knockdown restrained the tumor volume, tumor weight, and glycolysis in prostate cancer in vivo. Thus, STC1/Nrf2 pathway is a vital pathway to induce ferroptosis and suppress glycolysis in prostate cancer.
Clinical characteristics and prognostic value of EGFR mutation in stage I lung adenocarcinoma with spread through air spaces after surgical resection.
Gao MG, Wang SZ, Han KH … +2 more , Xie SN, Liu QY
Neoplasma · 2022 Dec · PMID 36591802 · Publisher ↗
The clinical data of stage I invasive lung adenocarcinoma patients with spread through air spaces (STAS) who underwent lobectomy from January 1, 2013 to January 1, 2016 at the Department of Thoracic Surgery of Hebei Medi...
The clinical data of stage I invasive lung adenocarcinoma patients with spread through air spaces (STAS) who underwent lobectomy from January 1, 2013 to January 1, 2016 at the Department of Thoracic Surgery of Hebei Medical University were analyzed retrospectively, and statistical analysis was carried out to explore their clinical features and prognostic value of EGFR mutation. A total of 280 patients were included in the study cohort, and EGFR mutations were detected in 154 patients. EGFR mutations were more common in non-smokers (p=0.045), females (p<0.001), without vascular tumor thrombus (p=0.037), and histological subtype LPA/APA/PPA (p=0.001). Multivariate analysis of the Cox risk regression model showed that EGFR gene mutation (p=0.807) was not an independent influencing factor of recurrence-free survival (RFS), but EGFR mutation was an independent influencing factor of overall survival (OS) (p=0.012), and OS of patients with EGFR mutation was better. The EGFR mutation also significantly increased the progression-free survival (PFS) of relapsed patients (p<0.001), but the PFS of relapsed EGFR mutation patients who received adjuvant chemotherapy after the operation was worse than that of patients who did not receive adjuvant chemotherapy (p=0.029). EGFR gene mutation is not a risk factor for postoperative recurrence in patients with stage I lung adenocarcinoma with STAS but the 5-year survival rate of patients with EGFR gene mutation is better than that of wild-type. Postoperative adjuvant chemotherapy for patients with EGFR mutation should be carefully considered.
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