J BUON [JOURNAL]
Sun
200 papers
Real-life data on first-line Sunitinib and Pazopanib therapy in metastatic renal cell carcinoma patients: a single center experience.
Topal A, Sayın S, Gokyer A … +6 more , Kucukarda A, Kostek O, Bekir Hacıoglu M, Uzunoglu S, Erdogan B, Cicin I
J BUON · 2021 · PMID 34565028
PURPOSE: In this study, we aimed to compare the data of sunitinib and pazopanib used in the first-line treatment of metastatic renal cell carcinoma (RCC) cases and to evaluate the effective factors in terms of survival....
PURPOSE: In this study, we aimed to compare the data of sunitinib and pazopanib used in the first-line treatment of metastatic renal cell carcinoma (RCC) cases and to evaluate the effective factors in terms of survival. METHODS: The records of 125 patients with metastatic RCC admitted between January 2005 and February 2018 were retrospectively analyzed and 63 patients who received pazopanib or sunitinib were included in the study while 62 patients were excluded due to insufficient data. Clinical and histological characteristics, treatment responses, progression-free survival (PFS), and overall survival (OS) of the patients were compared. RESULTS: Patients with metastatic RCC who received pazopanib or sunitinib as tyrosine kinase inhibitors (TKI) in first-line treatment were analyzed; 45 (71.4%) were male while 18 (28.6%) were female, and the median age was 60. 43 (68.3%) patients were treated with sunitinib and 20 (31.7%) with pazopanib. PFS of pazopanib and sunitinib were 10.6 and 7.2 months, respectively. Median OS was 14.5 months in patients receiving pazopanib and 13.6 months in those receiving sunitinib. There was no statistical difference in PFS and OS between both treatments. The median OS of clear-cell RCC was 15.2 months, while of non-clear-cell RCC was 7.7months. CONCLUSIONS: High ECOG score, non-clear-cell histology, presence of liver metastasis in metastatic RCC patients were found to be associated with shorter OS and PFS. Sunitinib and pazopanib produced similar OS and PFS rates in first-line treatment of metastatic RCC.
ADAMTS9-AS2: a potential diagnostic and prognostic hallmark in prostate cancer.
He L, Xiao Y, Ma L … +3 more , Zhao F, Yu T, Huang Y
J BUON · 2021 · PMID 34565027
PURPOSE: To explore the expression level and prognostic value of ADAMTS9-AS2 in prostate cancer (PCa). METHODS: ADAMTS9-AS2 levels in 110 paired PCa tissues and adjacent normal tissues were detected by quantitative real-...
PURPOSE: To explore the expression level and prognostic value of ADAMTS9-AS2 in prostate cancer (PCa). METHODS: ADAMTS9-AS2 levels in 110 paired PCa tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between ADAMTS9-AS2 level and clinical parameters of PCa was analyzed. ROC (receiver operating characteristics) curves were depicted for assessing the diagnostic value of ADAMTS9-AS2 in PCa. Through collecting 5-year follow-up data of PCa patients, survival analysis was performed by Kaplan-Meier method. Finally, Cox regression model was used to analyze factors affecting outcomes of PCa patients. RESULTS: ADAMTS9-AS2 was downregulated in PCa tissues than in adjacent normal ones. Its level was lower in PCa tissues with clinical stage III+IV or tumor size ≥3cm compared to those with stage I+II or tumor size <3cm. ROC curves verified the diagnostic value of ADAMTS9-AS2 in PCa (AUC=0.902, cut-off value=0.40, sensitivity=90.00%, specificity=79.09%, Youden index=0.6909). Kaplan-Meier method and log-rank test uncovered worse prognosis in PCa patients expressing low level of ADAMTS9-AS2. Clinical stage, tumor size and ADAMTS9-AS2 level were independent factors influencing prognosis of PCa. CONCLUSIONS: ADAMTS9-AS2 is downregulated in PCa and its low level is unfavorable to the disease prognosis. ADAMTS9-AS2 may be utilized as a potential diagnostic and prognostic hallmark of PCa.
A nomogram concerning immune infiltration and radiosensitivity to predict biochemical recurrence after radical radiation therapy in prostate cancer.
Qiu C, Zhou X, Chen Z … +1 more , Ren H
J BUON · 2021 · PMID 34565026
PURPOSE: To construct a nomogram concerning immune infiltration and radiosensitivity to predict biochemical recurrence (BCR) after radical radiation therapy in prostate cancer (PCa). METHODS: The Affymetrix microarray GS...
PURPOSE: To construct a nomogram concerning immune infiltration and radiosensitivity to predict biochemical recurrence (BCR) after radical radiation therapy in prostate cancer (PCa). METHODS: The Affymetrix microarray GSE116918 was acquired from the Gene Expression Omnibus (GEO) database. This cohort was grouped into biochemical recurrence ("BCR" group), among whom some patients developed metastatic recurrence ("MET" group), while the other patients were free from biochemical recurrence ("NO" group). Gene set enrichment analysis (GSEA) was performed. Immune infiltration was quantified by CIBERSORT, and infiltration score (IFS) and radiosensitivity score (RSS) were constructed. Cox multivariate regression coefficients were used to generate a nomogram. RESULTS: Compared to patients in the NO group, patients in the BCR group tended to be in a higher T stage (56.85% IN T1-2 VS. 43.15% IN T3-T4; <0.05). IFS was calculated based on the infiltration level of neutrophils, macrophages, plasmacytoid dendritic cells (pDC), activated dendritic cells (aDC), and CD56 bright NK cells. Patients in the IFS-low group had a significantly longer BCR-free survival than those in the IFS-high group (p<0.0001). RSS was calculated based on the expression levels of BRCA2, IGF1, BCL2L1, MAPK1, MAPK6, and MAPK13. Patients in the RSS-low group had a significantly longer BCR-free survival than those in the RSS-high group (p<0.0001). A nomogram predicting BCR after radical radiation therapy in PCa showed a 95% CI of [0.6584, 0.7928] for C-index, an AUC of 0.741 at 5 years, and fine calibration. CONCLUSIONS: In this study, we constructed a visual nomogram to predict BCR after radical radiation therapy in PCa with fine discriminatory and calibration capacity, which took elements, such as immune infiltration and radiosensitivity, into consideration for the first time.
Pancreatic cancer patients who cannot undergo curative surgery live as much as patients over 70 years old.
Serkan Y, Atike Pinar E, Cengiz Y … +3 more , Ahmet O, Ferhat E, Gulcan B
J BUON · 2021 · PMID 34565025
PURPOSE: Patients over the age of 65 constitute approximately 54% of newly diagnosed cancers and approximately 70% of cancer-related deaths. These patients aged ≥65 years, who form the majority of clinical practice, are...
PURPOSE: Patients over the age of 65 constitute approximately 54% of newly diagnosed cancers and approximately 70% of cancer-related deaths. These patients aged ≥65 years, who form the majority of clinical practice, are represented less in clinical studies than in real life. We designed this retrospective study to examine the treatment and response of patients to pancreatic cancer in patients over 70 years of age. METHODS: Our study is a retrospective study that included patients from 5 centers in Turkey. Inclusion criteria were being over the age of 18 years, diagnosed with pancreatic cancer, and with ECOG performance score between 0-2. These patients were divided into two groups according to their age. The classification was made as patients over 70 years of age in the first group (geriatric group) and patients under 70 years of age (<70 age group) in the second group. RESULTS: Overall survival of the <70 age group was statistically significantly longer (median 10 months vs 9.1 months p=0.027). When the patients who underwent only curative surgery were examined, the survival was statistically significant in favor of the <70 age group (median 20.96 months vs 14.5 months p=0.011). No statistically significant difference was found between the two groups in terms of the overall survival of patients with metastatic diagnosis (median 8.1 months vs 8.4 months p=0.182). CONCLUSION: The survival of patients with pancreatic cancer aged 70 and over was shorter than other age groups. While this difference was significant in patients who could undergo surgery at an early stage, it was not found in the metastatic patient group. Prospective larger-scale studies are needed to evaluate the treatment of geriatric patients better.
The WNT5A/ROR2 signaling pathway in pancreatic ductal adenocarcinoma (PDAC).
Remtisch L, Wiltberger G, Schierle K … +6 more , Yousef M, Thieme R, Jansen Winkeln B, Wittekind C, Gockel I, Lyros O
J BUON · 2021 · PMID 34565024
PURPOSE: WNT5A/ROR2 signaling pathway has been involved in many human cancers. Its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified yet. The purpose of this study was to determine the prognostic val...
PURPOSE: WNT5A/ROR2 signaling pathway has been involved in many human cancers. Its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified yet. The purpose of this study was to determine the prognostic value of WNT5A expression in conjunction with the ROR2 expression in the same PDAC human tissues. METHODS: We retrospectively analyzed by immunohistochemistry the WNT5A and ROR2 expression in117 paraffin-embedded PDAC specimens following surgical pancreatic resection. The prognostic value of WNT5A and ROR2 was assessed using Kaplan-Meier survival curves and multivariate Cox regression models. RESULTS: High ROR2 expression was detected in 65.8% (77/117) of PDAC tumors, in 28.2% (33/117) in tumor-stroma, and in 71.1% (65/90) of normal pancreatic tissue. High WNT5A expression was found in 76.9% (90/117) of tumors, in 59.0% (69/117) of tumor-stroma, and in 83.0% (73/88) of normal pancreatic tissue. Spearman's correlation coefficiency demonstrated weak association between ROR2 and WNT5A expression in tumor (r=0.184; p=0.047), and no association in stroma (r=0.036; p=0.699). Multivariate analysis showed that regional lymph node invasion and differentiation were independent prognostic factors of survival, while ROR2- and WNT5A expression were not. CONCLUSIONS: Variable expression patterns for ROR2 and WNT5A were demonstrated in PDAC and normal pancreatic tissues suggesting a role for WNT5A/ROR2 signalling pathway, not only in PDAC but also in the normal pancreatic tissue during inflammation. The lack of prognostic significance for ROR2 and WNT5A expression in our cohort, either alone or in subgroup analysis, underlines the complexity of their role in PDAC, which is highly dependent on the different molecular receptor-ligand tissue contexts.
hsa_circ_0005721 triggers proliferation, migration and invasion of osteosarcoma by upregulating the linear transcript TEP1.
Xu M, Sun X, Liu Y … +3 more , Chang L, Wang HT, Wang S
J BUON · 2021 · PMID 34565023
PURPOSE: This study aimed to illustrate the biological role of hsa_circ_0005721 in the development of osteosarcoma and the molecular mechanism. METHODS: hsa_circ_0005721 levels in 30 pairs of osteosarcoma and non-tumor t...
PURPOSE: This study aimed to illustrate the biological role of hsa_circ_0005721 in the development of osteosarcoma and the molecular mechanism. METHODS: hsa_circ_0005721 levels in 30 pairs of osteosarcoma and non-tumor tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments were conducted to assess the influence of hsa_circ_0005721 on proliferative, metastatic and apoptotic rates of osteosarcoma cells. The downstream target of hsa_circ_0005721 and their co-regulatory mechanism in malignant development of osteosarcoma were analyzed by dual-luciferase reporter assay and rescue experiments, respectively. RESULTS: hsa_circ_0005721 was upregulated in osteosarcoma tissues and cell lines. Knockdown of hsa_circ_0005721 suppressed proliferative and metastatic rates of U-2OS and Saos-2 cells, and stimulated apoptosis. Serving as a ceRNA, hsa_circ_0005721 upregulated the linear transcript TEP1 by competitively binding miR-16-5p, thus exerting its biological functions in regulating osteosarcoma development. CONCLUSIONS: This study for the first time identified the upregulated hsa_circ_0005721 in osteosarcoma, which triggers the malignant development of osteosarcoma by upregulating the linear transcript TEP1.
A potential diagnostic marker for osteosarcoma: hsa_circ_0005721.
Han Z, Mou Z, Jing Y … +2 more , Jiang R, Sun T
J BUON · 2021 · PMID 34565022
PURPOSE: To detect the expression level of hsa_circ_0005721 in osteosarcoma specimen and plasma of osteosarcoma patients, and to analyze the clinical significance of hsa_circ_0005721 as a diagnostic marker for osteosarco...
PURPOSE: To detect the expression level of hsa_circ_0005721 in osteosarcoma specimen and plasma of osteosarcoma patients, and to analyze the clinical significance of hsa_circ_0005721 as a diagnostic marker for osteosarcoma. METHODS: Expression levels of hsa_circ_0005721 in osteosarcoma specimen and osteosarcoma cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between hsa_circ_0005721 expression difference and overall survival in osteosarcoma was analyzed by Kaplan-Meier method. Expression level of hsa_circ_0005721 was stably downregulated in U-2OS and HOS cells by shRNA transfection. Proliferative potential in osteosarcoma cells regulated by hsa_circ_0005721 was assessed by colony formation and 5-Ethynyl-2'- deoxyuridine (EdU) assay. Differentially expressed hsa_circ_0005721 in the plasma of healthy controls, benign bone tumor patients and osteosarcoma patients was determined by qRT-PCR. The diagnostic capacity of hsa_circ_0005721 in osteosarcoma was examined by receiver operating characteristic (ROC) curves. RESULTS: hsa_circ_0005721 was upregulated in osteosarcoma specimen and osteosarcoma cell lines. High level of hsa_circ_0005721 predicted poor prognosis in osteosarcoma patients. In vitro experiments showed that knockdown of hsa_circ_0005721 suppressed proliferative ability in osteosarcoma cells. Compared with that in healthy controls and benign bone tumor patients, plasma level of hsa_circ_0005721 was higher in osteosarcoma patients. ROC curves demonstrated the diagnostic potential of hsa_circ_0005721 in osteosarcoma. CONCLUSIONS: hsa_circ_0005721 is upregulated in osteosarcoma samples, which acts as an oncogene responsible for aggravating the progression. hsa_circ_0005721 can be a promising diagnostic marker for osteosarcoma.
Double isocenter optimization with HD-MLC linear accelerator to treat extended fields in patients with head and neck cancers.
Saglam Y, Selek U, Bolukbasi Y … +9 more , Atasoy AI, Karakose F, Alpan V, Akdemir EY, Senyurek S, Kilic Durankus N, Sezen D, Kucuk A, Topkan E
J BUON · 2021 · PMID 34565021
PURPOSE: For departments with a congested patient burden or with a limited number of eligible LINACs, we investigated whether LINACS dedicated for SRS-SBRT with limited field high-definition (HD) multi-leaf collimator (M...
PURPOSE: For departments with a congested patient burden or with a limited number of eligible LINACs, we investigated whether LINACS dedicated for SRS-SBRT with limited field high-definition (HD) multi-leaf collimator (MLC) could help to carry this load, and utilized a double-isocenter (DI) optimization with a limited field size of HD-MLC to defeat the craniocaudal field size restriction to match treated plans in a wide-field MLC LINAC for head and neck cancer patients. METHODS: Fourteen patients with locally advanced head and neck cancers were included, previously treated with simultaneous integrated boost volumetric modulated arc treatment (VMAT) in 33 fractions of clinical target volumes (CTV) of 70Gy, 63Gy, and 57Gy, via single isocenter (SI) plans in Millennium MLC-120 of Varian Trilogy. The DI plans were generated on Pinnacle TPS to be delivered in HD 120 leaves MLC on Varian Truebeam. The organs at risk (OAR) doses and the prescription volume parameters were compared. RESULTS: The DI plans in HD-MLC LINACs were successfully matching the previously treated plans for OAR and CTV constraints. The CI (1.18 versus 1.26; p=0.004) and HI (0.23 versus 0.29; p<0.001) were significantly improved with DI, while the MUs (1321.5 versus 800.3; p<0.001) and the treatment delivery times (6.1 versus 3.7 min; p<0.001) per fraction increased modestly with DI compared to SI, respectively. CONCLUSIONS: We revealed that DI optimization plans prepared for HD-MLC could effectively accomplish our goal dosimetrically in locoregionally advanced head and neck cases, despite a modest increase in the MU and treatment delivery times per fraction. This technique may provide an alternative in case of downtimes of standard MLC systems or a standalone treatment machine in case of high volumes requiring extended-field IMRT procedures, or possibly shorten the lengthy waiting times in facilities with limited SRS or SBRT patients.
VASN promotes proliferation of laryngeal cancer cells via YAP/TAZ.
Liu H, Kong W, Wen S … +3 more , Wu J, Yin X, Liu Y
J BUON · 2021 · PMID 34565020
PURPOSE: To explore whether vasorin protein (VASN) can affect the proliferation of laryngeal cancer cells through the regulation of yes-associated protein (YAP)/TAZ (transcriptional co-activator with PDZ binding motif),...
PURPOSE: To explore whether vasorin protein (VASN) can affect the proliferation of laryngeal cancer cells through the regulation of yes-associated protein (YAP)/TAZ (transcriptional co-activator with PDZ binding motif), and then promote the development of laryngeal cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of VASN in laryngeal carcinoma tissues and different T-stage tumor patients, and the correlation between VASN expression and clinicopathological features was analyzed. The diagnostic value of VASN for laryngeal cancer was assessed by receiver operating characteristic (ROC) analysis. Kaplan-Meier method was used to plot the survival curves of patients with different VASN expression levels. After knocking down VASN in Hep-2 cells or in overexpressing VASN in TU212 cells, cell viability, proliferation ability and protein expression level of YAP/TAZ were detected by cell counting kit-8 (CCK-8), plate cloning assay and Western blot. Furthermore, YAP was overexpressed or knocked down simultaneously to evaluate its effect on the viability and proliferation ability of cells. RESULTS: The expression of VASN in laryngeal carcinoma was significantly higher than that in the normal control group, while, at the same time, the expression of VASN in the t3+t4 tumor patients was significantly higher than that in the t1+t2 tumors. We also found that the expression level of VASN was closely related to N stage, T stage, and lymph node metastasis, suggesting that VASN had a certain diagnostic value for laryngeal cancer. After knocking down VASN in cells, the cell viability, proliferative capacity and YAP/TAZ protein expression level decreased significantly. Besides, overexpressing YAP could reverse the inhibition of cell viability and proliferation ability caused by VASN knockdown. CONCLUSIONS: VASN can promote the development of laryngeal cancer by affecting the expression of YAP/TAZ.
METTL3 participates in glioma development by regulating the methylation level of COL4A1.
Han J, Du S, Wu C … +5 more , Qiu M, Su L, Zhao Z, Cheng S, Tao W
J BUON · 2021 · PMID 34565019
PURPOSE: The role of RNA methylation in human cancers has emerged. Its biological function in glioma development is explored in the present study. METHODS: Differential levels and prognostic potentials of COL4A1 and METT...
PURPOSE: The role of RNA methylation in human cancers has emerged. Its biological function in glioma development is explored in the present study. METHODS: Differential levels and prognostic potentials of COL4A1 and METTL3 in glioma were analyzed by bioinformatic method. The regulatory effect of METTL3 on COL4A1 was assessed through qRT-PCR, MeRIP and dual-luciferase reporter assay. Their biological functions in influencing proliferative and metastatic capacities of glioma cells were examined by EdU, colony formation and Transwell assay, respectively. RESULTS: COL4A1 was upregulated in glioma tissues, and METTL3 was downregulated. Knockdown of METTL3 in U87 and U251 cells could reduce the methylation level of COL4A1 and upregulate its expression level. Intervention of COL4A1 suppressed proliferative and metastatic capacities of glioma cells, while intervention of METTL3 yielded the opposite results. CONCLUSION: METTL3 reduces the methylation level of COL4A1 and upregulates its expression level, which further stimulates the malignant development of glioma. METTL3/COL4A1 can be potential therapeutic targets of glioma.
Effects of triptolide on radiosensitivity of human glioma cells and its mechanism.
Shu M, Li C, Zhong C … +5 more , Huang T, Wang X, Tan Y, Zhao W, Xie X
J BUON · 2021 · PMID 34565018
PURPOSE: To study the effect of triptolide (TP) on radiosensitivity of human glioma U251 cells and its mechanism, so as to provide new ideas and methods for the radiotherapy of glioma. METHODS: U251 cells were treated wi...
PURPOSE: To study the effect of triptolide (TP) on radiosensitivity of human glioma U251 cells and its mechanism, so as to provide new ideas and methods for the radiotherapy of glioma. METHODS: U251 cells were treated with 10, 50, 100 nmol/L TP at different concentrations and irradiated with 0, 2, 4, 6, 8 Gy X-ray. The radiosensitivity of cells in each group were detected by MTT. U251 cells were then divided into control group, 10 nmol/L TP group, 4 Gy radiation group, 10 nmol/L TP + 4 Gy radiation group. The formation ability of U251 cells in each group was detected by colony formation assay. Flow cytometry was used to detect cell cycle and apoptosis in each group. Western blot was used to detect the changes of PI3K/Akt signal pathway in each group. RESULTS: When 10, 50, 100 nmol/L TP were combined with 2, 4, 6, 8 Gy X-ray, the proliferation inhibition rate of U251 cells in each group increased significantly (p<0.05); compared with 10 nmol/L TP alone group and 4 Gy radiation alone group, the colony formation ability rate of U251 cells in 10 nmol/L TP + 4Gy radiation combined group decreased significantly (p<0.05), the cell cycle was blocked in G1 phase, and the apoptosis rate was significantly reduced (p<0.05). The level of p-pi3k and p-Akt decreased significantly (p<0.05). CONCLUSION: Triptolide could significantly increase the radiosensitivity of human glioma U251 cells and play a role by inhibiting the PI3K/Akt signal pathway.
Targeted massively parallel sequencing in the management of cytogenetically normal lymphoid malignancies.
Ikbal Atli E, Gurkan H, Atli E … +5 more , Yalcintepe S, Demir S, Eker D, Kalkan R, Muzaffer Demir A
J BUON · 2021 · PMID 34565017
The variations in clinical and biological background of lymphoid malignancies trigger researchers to try to find out novel therapeutic targets. A typical treatment includes multiagent chemotherapy and/or targeted therapy...
The variations in clinical and biological background of lymphoid malignancies trigger researchers to try to find out novel therapeutic targets. A typical treatment includes multiagent chemotherapy and/or targeted therapy in the light of driver mutations. Next generation sequencing (NGS) plays a pivotal role during the identification of genetic alterations in lymphoid malignancies. A total of 52 patients [30 men (58%) and 22 women (42%)] having normal cytogenetic and FISH results were enrolled in this study. Usage of NGS based targeted sequencing could confirm or support a particularly preferred diagnosis (41/52, 78%) or make a differential diagnosis in cases of interference. Notably, in 11 out of these 52 cases (21%), the initial suspect diagnosis was not supported by the NGS result and thereby had to be reconsidered. In this study, we highlight the importance of targeted NGS panel testing for diagnosis, prognosis and treatment decision in highly selected instances of lymphoid malignancies and lymphoproliferative disorders in which histopathology and more conventional molecular analyses remain inconclusive.
Pralatrexate experience in PTCL: A multicenter retrospective study from Turkey.
Sinan Dal M, Merdin A, Erkurt MA … +17 more , Ekinci Ö, Albayrak M, Kabukcu Hacıoglu S, Kaya A, Dogu MH, Hindilerden F, Sarici A, Merter M, Reis Aras M, Akgun Caglıyan G, Kizil Cakar M, Aydogdu I, Kuku I, Korkmaz S, Ulas T, Eser B, Altuntas F
J BUON · 2021 · PMID 34565016
PURPOSE: Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients...
PURPOSE: Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients receiving pralatrexate therapy in Turkey, contributing to the literature on the effectiveness of pralatrexate therapy in peripheral T-cell lymphomas by determining the response levels of such patients to the therapy. The study also attempts to clinically examine the major side effects observed in patients during treatment with pralatrexate. METHODS: The study included patients with peripheral T-cell lymphoma followed up in the hematology units of several hospitals in Turkey. Overall, 20 patients aged 18 and over were included in the study. RESULTS: The median age at the time of diagnosis was 58.5 years. PTCL-NOS (Peripheral T-cell lymphoma, not otherwise specified) subtype was in 40% of patients, making the PTCL-NOS the most common subtype in the study. In general, most patients were diagnosed with disease at an advanced stage. Pralatrexate therapy was given to the patients at a median treatment line of 3.5. Pralatrexate dose reduction was required in only 3 patients (15%). Response to pralatrexate therapy with partial remission (PR) and above was observed in 11 (55%) of the patients. CONCLUSION: Pralatrexate seemed to be a promising novel treatment in relapsed refractory PTCL patients. However, patients receiving pralatrexate should be followed up carefully for skin reactions, mucosal side effects, thrombocytopenia and neutropenia.
TP73-AS1 promotes malignant progression of NK/T cell lymphoma by regulating DKK1 methylation.
Zhang H, Huang Q
J BUON · 2021 · PMID 34565015
PURPOSE: Long non-coding RNA (lncRNA) TP73-AS1 is abnormally expressed in multiple types of tumors, which is able to mediate tumor cell signals. This study aims to explore the role of TP73-AS1 in affecting biological fun...
PURPOSE: Long non-coding RNA (lncRNA) TP73-AS1 is abnormally expressed in multiple types of tumors, which is able to mediate tumor cell signals. This study aims to explore the role of TP73-AS1 in affecting biological functions of NK/T-cell lymphoma (NKTCL) and DKK1 methylation. METHODS: TP73-AS1 levels in peripheral blood of NKTCL patients and healthy volunteers was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of TP73-AS1, proliferative and migratory abilities in SNK-6 and HANK-1 cells were assessed by cell counting kit-8 (CCK-8) and Transwell assay, respectively. Regulatory effect of TP73-AS1 on DKK1 methylation in NKTCL cells was evaluated through methylation-specific PCR (MSP), dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP). Rescue experiments were conducted to further validate the interaction between TP73-AS1 and DKK1. RESULTS: TP73-AS1 level was higher in peripheral blood of NKTCL patients than that of healthy volunteers. Knockdown of TP73-AS1 in vitro weakened proliferative and migratory functions of NKTCL cells. TP73-AS1 induced methylation of DKK1 promoter through DNMT1/DNMT3, thus regulating NKTCL cell functions. CONCLUSIONS: TP73-AS1 level was higher in peripheral blood of NKTCL patients. Through inducing methylation of DKK1 promoter, TP73-AS1 aggravates the malignant progression of NKTCL.
Results of upfront surgery in a mixed stage population of patients with esophageal carcinoma: early outcome and long term survival.
Prokakis C, Maliouki M, Koletsis E … +6 more , Athanasios K, Chatzimichalis A, Baltayiannis N, Charokopos N, Thomopoulos K, Dougenis K
J BUON · 2021 · PMID 34565014
PURPOSE: To evaluate early outcome and long term survival in a mixed stage population of patients undergoing upfront esophagectomy for esophageal cancer. METHODS: Retrospective analysis of the data of 92 patients who und...
PURPOSE: To evaluate early outcome and long term survival in a mixed stage population of patients undergoing upfront esophagectomy for esophageal cancer. METHODS: Retrospective analysis of the data of 92 patients who underwent esophagectomy (thoracoabdominal: 76, Ivor-lewis: 16) between 1998 and 2017. Tumors were located in gastro-esophageal junction (52), lower third (31) and middle third (9) of the esophagus. Histology was: 73 adenocarcinomas and 19 squamous cell carcinomas. The stomach was used for reconstruction in 90 patients. A neck anastomosis was performed in 7 patients. End points of the study included: mortality, morbidity and long term survival. Kaplan-Meier and Cox regression analyses were used to identify prognostic factors for survival. RESULTS: The mortality was 10.9% and 29 patients presented 49 complications. Anastomotic dehiscence occurred in 17.4% of the patients and represented the most common cause of death with mortality of 37.5%. Reoperation was necessary in 14 patients. Median survival reached 25 months with 3 and 5 year survival of 30.5% and 21% respectively. Early stage tumors, absence of nodal disease, well differentiated carcinomas and lymph node ratio ≤ 0.2 were associated with 5 year survival of 82.6%, 81.6%, 83.3% and 40.4% respectively. In multivariate analysis early stage disease (OR: 15.746, 95%CI: 4.332-58.579, p < 0.001) and lymph node ratio (OR: 1.700 95%CI: 1.051-2.752, p = 0.031) were statistically associated with long term survival. CONCLUSIONS: Our results support the role of upfront surgery as the treatment of choice in early stage esophageal carcinomas without or with low nodal involvement.
MANCR drives esophageal carcinoma progression by targeting PDE4D.
Fan J, Wang F
J BUON · 2021 · PMID 34565013
PURPOSE: To explore the role of lncRNA MANCR in regulating in vitro proliferation and apoptosis in esophageal carcinoma cells and in vivo growth of esophageal carcinoma in nude mice. METHODS: MANCR levels in 15 pairs of...
PURPOSE: To explore the role of lncRNA MANCR in regulating in vitro proliferation and apoptosis in esophageal carcinoma cells and in vivo growth of esophageal carcinoma in nude mice. METHODS: MANCR levels in 15 pairs of esophageal carcinomas and non-tumoral tissues were detected by qRT-PCR. In vitro regulations of MANCR on proliferative and apoptotic potentials in TE-1 and EC-109 cells were explored by CCK-8, colony formation assay and flow cytometry. In addition, dual-luciferase reporter assay and rescue experiments were conducted to clarify the potential mechanisms of MANCR on regulating PDE4D. Finally, in vivo role of MANCR in mediating esophageal carcinoma growth was determined in nude mice implanted with EC-109 cells. RESULTS: MANCR was highly expressed in esophageal carcinomas tissues than non-tumoral ones. MANCR promoted proliferative ability and inhibited apoptosis in TE-1 and EC-109 cells. In nude mice with xenografted esophageal carcinoma, knockdown of MANCR markedly slowed down tumor growth. PDE4D was the target gene binding MANCR, which was downregulated in esophageal carcinoma tissues. Its level was negatively regulated by MANCR. Importantly, PDE4D could abolish the role of MANCR in stimulating the malignant progression of esophageal carcinoma. CONCLUSIONS: LncRNA MANCR is upregulated in esophageal carcinoma cases. Through negatively regulating PDE4D level, MANCR stimulates proliferative ability and inhibits apoptosis in esophageal carcinoma, thus driving the malignant progression.
Chemoradiotherapy followed by surgery versus observation in esophageal squamous cell carcinoma.
Sakin A, Sahin S, Aldemir MN … +2 more , Iliklerden UH, Kotan MC
J BUON · 2021 · PMID 34565012
PURPOSE: We aimed to examine the effect of esophagectomy after chemoradiotherapy (CRT) or non-surgical follow-up after CRT in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of...
PURPOSE: We aimed to examine the effect of esophagectomy after chemoradiotherapy (CRT) or non-surgical follow-up after CRT in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 653 patients under follow-up for locally advanced ESCC between 2010-2019 were reviewed for enrollment. Patients with no distant metastasis at the time of diagnosis who underwent esophagectomy or were taken under observation following CRT were included in the study. Overall, 127 eligible patients were included, 55 of whom were male (43.3%) and 72 female (56.7%). RESULTS: After CRT, 59 patients (53.5%) had undergone surgery and 68 (46.5%) were taken under observation. Median disease-free survival (mDFS) was not reached in the group that underwent surgery and was 13 months in the observation group (p<0.001). Median overall survival (mOS) was significantly longer in the operated group (p=0.006). There was no statistically significant difference in DFS and OS between patients who underwent surgery and those included in the observation group after achieving clinical and pathological complete response following CRT (p=0.119, p=0.699, respectively). The multivariate analysis identified surgery and increased CRT response as the factors that affect DFS (p=0.042, p<0.001, respectively). CONCLUSION: In this study, surgery provided no additional benefit on survival in locally advanced ESCC patients with complete response while prolonged survival was observed in those without complete response. Key words: esophageal cancer, chemoradiotherapy, squamous cell carcinoma, observation .
Diagnostic and prognostic potentials of AK126393 in bladder cancer.
Guan Y, Zhang G, Li Z … +3 more , Ai X, Jia Z, Teng J
J BUON · 2021 · PMID 34565011
PURPOSE: To elucidate the diagnostic and prognostic potentials of lncRNA AK126393 in bladder cancer. METHODS: The expression levels of AK126393 in 60 matched bladder cancer tissues and paracancerous tissues were determin...
PURPOSE: To elucidate the diagnostic and prognostic potentials of lncRNA AK126393 in bladder cancer. METHODS: The expression levels of AK126393 in 60 matched bladder cancer tissues and paracancerous tissues were determined. In addition, AK126393 level in bladder cancer patients with different tumor staging (stage I-II and stage III-IV) was detected as well. Receiver operating characteristic (ROC) was introduced for assessing the diagnostic potential of AK126393 in bladder cancer. Based on the cut-off value of AK126393 in the enrolled 60 bladder cancer patients, they were assigned into high and low expression groups, respectively. Correlation between AK126393 level and pathological indexes of bladder cancer patients was analyzed by chi-square test. By collecting 5-year follow-up data, Kaplan-Meier method was conducted to evaluate survival influenced by AK126393. Moreover, Cox regression model was applied for analyzing potential factors affecting the prognosis of bladder cancer patients. RESULTS: AK126393 was downregulated in bladder cancer tissues than in paracancerous ones. Its level remained lower in bladder cancer patients with stage III-IV relative to those with stage I-II. ROC illustrated the diagnostic potential of AK126393 in bladder cancer (AUC=0.8647, diagnosis threshold=2.03, sensitivity=76.7%, specificity=96.7%, Youden index=0.734). Besides, lower level of AK126393 was observed in bladder cancer patients with stage III-IV, lymph node metastasis or high-level differentiation. Kaplan-Meier curves demonstrated worse prognosis in bladder cancer patients expressing low level of AK126393. Cox regression analysis showed that AK126393 level, TNM staging, lymph node metastasis and tumor differentiation were independent risk factors influencing the prognosis of bladder cancer. CONCLUSIONS: AK126393 is downregulated in bladder cancer and closely linked to high rate of metastasis, advanced stage and poor prognosis. AK126393 may serve as diagnostic and prognostic hallmark in bladder cancer.
Biological functions of miR-363-3p/BTG2 in the metastasis of bladder cancer.
Li P, Yu Y, Wang X … +4 more , Hu K, Wang Y, Li F, Zhang H
J BUON · 2021 · PMID 34565010
PURPOSE: This study aimed to detect the differential expression of microRNA-363-3p (miR-363-3p) in bladder cancer (BC) samples and to explore its influence on metastasis of BC cells. METHODS: Expression level of miR-363-...
PURPOSE: This study aimed to detect the differential expression of microRNA-363-3p (miR-363-3p) in bladder cancer (BC) samples and to explore its influence on metastasis of BC cells. METHODS: Expression level of miR-363-3p in 70 cases of BC tissues and paracancerous tissues was detected. After establishing miR-363-3p overexpression model in 253j and RT4 cells, their migratory ability was assessed by Transwell and wound healing assay. The interaction between miR-363-3p and its downstream gene was predicted online and further confirmed by luciferase assay. Their involvement in regulating metastasis of BC cells was finally explored. RESULTS: MiR-363-3p was downregulated in BC tissues compared with that in the paracancerous tissues. Overexpression of miR-363-3p markedly weakened migratory ability in BC cells. BTG2 was the downstream gene binding miR-363-3p. In addition, overexpression of BTG2 reversed the inhibitory effect of miR-363-3p on BC cell migration. CONCLUSIONS: MiR-363-3p is lowly expressed in BC samples. It weakens in vitro migratory ability in BC cells through downregulating BTG2.
Circ_0006948 drives the malignant development of bladder cancer via activating the epithelial-mesenchymal transition.
Liu F, Wang N, Wei J … +3 more , Xue M, Liu Y, Dong R
J BUON · 2021 · PMID 34565009
PURPOSE: To detect the expression characteristic of circ_0006948 in bladder cancer (BC), and to analyze its relationship with pathological parameters and prognosis in BC patients. In addition, molecular mechanisms of cir...
PURPOSE: To detect the expression characteristic of circ_0006948 in bladder cancer (BC), and to analyze its relationship with pathological parameters and prognosis in BC patients. In addition, molecular mechanisms of circ_0006948 on driving the malignant progression of BC by activating epithelial-mesenchymal transition (EMT) was explored. METHODS: Circ_0006948 levels in 72 BC and paracancerous tissues were detected, and their relationship with pathological parameters and prognosis in BC patients was analyzed by chi-square test. After establishing circ_0006948 knockdown model in 253j and T24 cells, phenotype changes were assessed by cell counting kit-8 (CCK-8), transwell and wound healing assay. Regulatory effects of circ_0006948 on EMT-associated gene expressions in BC cells were determined by Western blot. Finally, the interaction between circ_0006948 and N-cadherin was evaluated by rescue experiments. RESULTS: Circ_0006948 was upregulated in BC tissues and cell lines. High level of circ_0006948 indicated advanced tumor stage, high rates of lymph node metastasis and distant metastasis, and poor prognosis in BC. Knockdown of circ_0006948 reduced proliferative and metastatic abilities in BC cells. The key protein in the EMT signaling E-cadherin was upregulated by knockdown of circ_0006948 in BC cells, while N-cadherin, Vimentin, β-catenin and MMP-9 were downregulated. The interaction between circ_0006948 and N-cadherin was identified, and they were co-responsible for the malignant development of BC. CONCLUSIONS: Circ_0006948 is upregulated in BC samples, and it is closely linked to tumor stage, metastasis and prognosis in BC patients. It drives proliferative and metastatic abilities in BC cells by activating EMT.
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