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1.
J Med Case Rep ; 18(1): 441, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39272123

ABSTRACT

BACKGROUND: Ogden type V tibial tubercle avulsion fracture is an unusual type of physial injury. Thus, little is known about its mechanism of injury and treatment. The type of osteosynthesis is variable and depends on the experience of the surgeon. We commonly used cancellous screws fixation combined with tension band wiring for displaced fracture of the anterior tibial tuberosity. CASE PRESENTATION: The present manuscript describes a case of a Han nationality 13-year-old boy who presented with severe pain of the left knee, which began after landing following a high jump. He had no significant past medical history apart from a high body mass index of 30.3. Radiographs revealed that he had an unusual Ogden type V tibial tubercle avulsion fracture. He was treated by open reduction and combined fixation with cannulated screws and tension-band wiring. After 3 months, the fracture healed without any complications or knee symptoms with full range of motion. He underwent reoperation for symptomatic hardware, which was removed at 5 months after initial surgery, and returned to his prior level of sporting activity at 1 year follow-up. CONCLUSION: Our case suggests that excellent functional outcome could be achievable by open reduction with the combination of internal fixation and tension-band wiring for Ogden type V tibial tubercle avulsion fracture. This type of osteosynthesis could not only achieve anatomical reduction and stable fixation for such fractures, but also avoid further damage to the proximal tibial epiphysis, which prevents serious complications, such difference in leg length.


Subject(s)
Bone Screws , Fracture Fixation, Internal , Fractures, Avulsion , Tibial Fractures , Humans , Male , Adolescent , Fracture Fixation, Internal/methods , Tibial Fractures/surgery , Tibial Fractures/diagnostic imaging , Fractures, Avulsion/surgery , Fractures, Avulsion/diagnostic imaging , Treatment Outcome , Radiography , Bone Wires , Range of Motion, Articular , Reoperation , Open Fracture Reduction/methods
2.
Cancer Genomics Proteomics ; 21(5): 523-532, 2024.
Article in English | MEDLINE | ID: mdl-39191496

ABSTRACT

BACKGROUND/AIM: Patients diagnosed with advanced metastatic colorectal cancer (CRC) confront a bleak prognosis characterized by low survival rates. Anoikis, the programmed apoptosis resistance exhibited by metastatic cancer cells, is a crucial factor in this scenario. MATERIALS AND METHODS: We employed bulk flow cytometry and RT-qPCR assays, conducted in vivo experiments with mice and zebrafish, and analyzed patient tissues to examine the effects of the B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1)-midkine (MDK) axis on the cellular response to anoikis. Bmi1 is pivotal in tumorigenesis. This study elucidated the involvement of Bmi1 in conferring anoikis resistance in CRC and explored its downstream targets associated with metastasis. RESULTS: Elevated levels of Bmi1 expression correlated with distant metastasis in CRC. Suppression of Bmi1 significantly diminished the metastatic potential of CRC cells. Inhibition of Bmi1 led to an increase in the proportion of apoptotic SW620 cells detached from the matrix. This effect was further enhanced by the addition of irinotecan, a topoisomerase I inhibitor. Furthermore, Bmi1 was found to synergize with MDK in modulating CRC viability, with consistent expression patterns observed in in vivo models and clinical tissue specimens. In summary, Bmi1 acted as a regulator of CRC metastatic capability by conferring anoikis resistance. Additionally, it collaborated with MDK to facilitate invasion and distant metastasis. CONCLUSION: Targeting Bmi1 may offer a promising adjunctive therapeutic strategy when administering traditional chemotherapy regimens to patients with advanced CRC.


Subject(s)
Anoikis , Colorectal Neoplasms , Neoplasm Metastasis , Polycomb Repressive Complex 1 , Adult , Aged , Animals , Female , Humans , Male , Mice , Middle Aged , Anoikis/drug effects , Cell Line, Tumor , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic/drug effects , Polycomb Repressive Complex 1/metabolism , Polycomb Repressive Complex 1/genetics , Polycomb Repressive Complex 1/antagonists & inhibitors , Zebrafish
3.
Am J Cancer Res ; 14(6): 3171-3185, 2024.
Article in English | MEDLINE | ID: mdl-39005677

ABSTRACT

Early detection of cancer recurrence using specific biomarkers remains a clinically unmet need, although methodologies for monitoring tumor markers, cell-free DNA, and circulating tumor cells have been established for decades. Tumor recurrence develops in metastatic or dormant cancer cells under continuous immune surveillance. Alterations in the population and function of immune cells may contribute to cancer recurrence. Here, we utilized an animal model to imitate breast tumor recurrence after surgical resection and investigated the abundance and gene expression profiles of immune cells using NanoString analysis. Bioinformatic analysis of a published single-cell RNA sequencing database of myeloid-derived suppressor cells (MDSCs) was performed to identify common targets between the two studies. Identified biomarkers were validated using human peripheral blood mononuclear cell (PBMC) datasets. The inhibitory effect of MDSCs on T-cell proliferation was assessed in vitro. Our data demonstrated that the number of MDSCs significantly increased during recurrence. Comparison of our NanoString data with a single-cell RNA sequencing dataset of MDSCs in another spontaneous breast cancer model identified colony-stimulating factor 3 receptor (Csf3r)-positive MDSCs as a potential marker for predicting tumor relapse. We validated our findings using two previously published PBMC databases of patients with breast cancer with or without recurrence and confirmed the elevated MDSC gene signature and CSF3R expression in patients with tumor recurrence. 35 patients with breast cancer were also included in our study, that patients with higher levels of CSF3R had worse survival. In vitro experiments demonstrated that Csf3r + MDSCs exhibited enhanced reactive oxygen species (ROS) levels and robust T-cell suppression ability. We conclude that an increase in CSF3R + MDSCs is a potential biomarker for early detection of tumor recurrence in patients with breast cancer.

4.
Life Sci ; 353: 122914, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39004275

ABSTRACT

AIMS: Colorectal cancer (CRC) remains a major global health issue, with metastatic cases presenting poor prognosis despite advances in chemotherapy and targeted therapy. Irinotecan, a key drug for advanced CRC treatment, faces challenges owing to the development of resistance. This study aimed to understand the mechanisms underlying irinotecan resistance in colorectal cancer. MAIN METHODS: We created a cell line resistant to irinotecan using HT29 cells. These resistant cells were utilized to investigate the role of the CDK7-MDK axis. We employed bulk RNA sequencing, conducted in vivo experiments with mice, and analyzed patient tissues to examine the effects of the CDK7-MDK axis on the cellular response to irinotecan. KEY FINDINGS: Our findings revealed that HT29 cells resistant to irinotecan, a crucial colorectal cancer medication, exhibited significant phenotypic and molecular alterations compared to their parental counterparts, including elevated stem cell characteristics and increased levels of cytokines and drug resistance proteins. Notably, CDK7 expression was substantially higher in these resistant cells, and targeting CDK7 effectively decreased their survival and tumor growth, enhancing irinotecan sensitivity. RNA-seq analysis indicated that suppression of CDK7 in irinotecan-resistant HT29 cells significantly reduced Midkine (MDK) expression. Decreased CDK7 and MDK levels, achieved through siRNA and the CDK7 inhibitor THZ1, enhanced the sensitivity of resistant HT29 cells to irinotecan. SIGNIFICANCE: Our study sheds light on how CDK7 and MDK influence irinotecan resistance in colorectal and highlights the potential of MDK-targeted therapies. We hypothesized that irinotecan sensitivity and overall treatment efficacy would improve by inhibiting MDK. This finding encourages a careful yet proactive investigation of MDK as a therapeutic target to enhance outcomes in colorectal cancer patients.


Subject(s)
Colorectal Neoplasms , Cyclin-Dependent Kinase-Activating Kinase , Cyclin-Dependent Kinases , Drug Resistance, Neoplasm , Irinotecan , Irinotecan/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/genetics , Humans , Animals , Drug Resistance, Neoplasm/drug effects , Mice , HT29 Cells , Cyclin-Dependent Kinases/metabolism , Cyclin-Dependent Kinases/antagonists & inhibitors , Cyclin-Dependent Kinases/genetics , Mice, Nude , Xenograft Model Antitumor Assays , Gene Expression Regulation, Neoplastic/drug effects , Mice, Inbred BALB C , Female , Cell Proliferation/drug effects
5.
EFORT Open Rev ; 9(6): 556-566, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828976

ABSTRACT

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

6.
Trauma Case Rep ; 52: 101040, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38784218

ABSTRACT

A 28-year-old man involved in a serious motorcycle accident was admitted to our hospital with comminuted fractures of the ipsilateral femoral shaft and tibial shaft, as well as multiple fractures of the right lower limb, including the proximal fibula, medial malleolus, and the third and fourth distal metatarsals. In addition, the patient suffered a skin contusion and laceration of the right foot. On the first day of admission, this patient suddenly developed tachycardia, pyrexia, and tachypnoea, and was immediately transferred to the ICU for further treatment due to a CT-diagnosed pulmonary fat embolism (FE). As a symptomatic treatment, he received a prophylactic dose of low-molecular-weight heparin for 10 days, after which his condition improved. A Doppler ultrasound of the lower leg and a follow-up chest CT angiography were performed, which excluded any remaining thrombus and verified that the pulmonary FE had improved without deterioration. Closed-reduction and retrograde intramedullary nailing were performed for the femoral shaft fractures, while antegrade intramedullary nailing was performed for the tibial shaft fractures under general anaesthesia. In the three-year follow-up, the patient had recovered with good function of the right limb, without any respiratory discomfort. Both the femoral and tibial shaft fractures finally resolved without any further treatment. Ipsilateral femoral and tibial shaft fractures should undergo surgical stabilisation as early as possible to avoid pulmonary FEs. It is still controversial whether intramedullary nailing is suitable for floating knee injuries complicated by pulmonary FEs. However, if patients with pulmonary FEs require intramedullary nailing, we suggest that surgery should be performed after at least one week of anticoagulant use, when patient vital signs are stable and there is no sign of dyspnoea. In addition, patients should try to avoid reaming during the operation to prevent and decrease "second hit" for the lung.

7.
In Vivo ; 38(3): 1143-1151, 2024.
Article in English | MEDLINE | ID: mdl-38688621

ABSTRACT

BACKGROUND/AIM: Following the National Comprehensive Cancer Network guidelines, radiotherapy is administered after breast-conserving surgery (BCS) in patients with more than four positive lymph nodes. Four positive lymph nodes are typically considered an indicator to assess disease spread and patient prognosis. However, the subjective counting of positive axillary lymph nodes underscores the need for biomarkers to improve diagnostic precision and reduce the risk of unnecessary treatments. Loss of E-cadherin expression is associated with cancer metastasis, but its potential as a predictive marker for cancer treatment remains uncertain. This study aimed to investigate the validity of E-cadherin as a reference for adjuvant radiotherapy in breast cancer patients with positive lymph nodes post-mastectomy. MATERIALS AND METHODS: Immunohistochemistry was performed on 60 clinical tissue specimens to assess these implications. RESULTS: Although no significant result was found in a single E-cadherin subgroup (low, medium, and high subgroups according to the X-tile algorithm), the proposed multivariate model, including the E-cadherin category, breast cancer subtype, and tumor size, yielded satisfactory recurrence risk estimation results for patients undergoing BCS. Patients with a low E-cadherin category, triple-negative breast cancers, and tumor size over 5 cm could have an increased risk of recurrence. CONCLUSION: Our study proposed a multivariate model that serves as a candidate prognostic factor for recurrence-free survival in patients undergoing BCS and radiotherapy. Utilizing this model for patient stratification in high-risk diseases and as a standard for assessing postoperative intensified therapy can potentially improve patient outcomes.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Cadherins , Mastectomy, Segmental , Neoplasm Recurrence, Local , Humans , Female , Cadherins/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/metabolism , Middle Aged , Prognosis , Aged , Adult , Immunohistochemistry , Lymphatic Metastasis , Neoplasm Staging
8.
J Pers Med ; 14(3)2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38540967

ABSTRACT

Gastrointestinal (GI) cancers are some of the main public health threats to the world. Even though surgery, chemotherapy, and targeted therapy are available for their treatments, these approaches provide limited success in reducing mortality, making the identification of additional therapeutic targets mandatory. Chromatin remodeling in cancer has long been studied and related therapeutics are widely used, although less is known about factors with prognostic and therapeutic potential in such areas as gastrointestinal cancers. Through applying systematic bioinformatic analysis, we determined that out of 31 chromatin remodeling factors in six gastrointestinal cancers, only PR/SET domain 1 (PRDM1) showed both expression alteration and prognosis prediction. Analyses on pathways, therapies, and mediators showed that cell cycle, bromodomain inhibitor IBET151, and BET protein BRD4 were, respectively involved in PRDM1-high stomach cancer, while cell line experiments validated that PRDM1 knockdown in human stomach cancer cell line SNU-1 decreased its proliferation, BRD4 expression, and responsiveness to IBET151; accordingly, these results indicate the contribution by PRDM1 in stomach cancer formation and its association with BRD4 modulation as well as BET inhibitor treatment.

9.
Biomedicines ; 11(12)2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38137334

ABSTRACT

The treatment of head and neck squamous cell carcinomas (HNSCCs) is multimodal, and chemoradiotherapy (CRT) is a critical component. However, the availability of predictive or prognostic markers in patients with HNSCC is limited. Inflammation is a well-documented factor in cancer, and several parameters have been studied, with the neutrophil-to-lymphocyte ratio (NLR) being the most promising. The NLR is the most extensively researched clinical biomarker in various solid tumors, including HNSCC. In our study, we collected clinical and next-generation sequencing (NGS) data with targeted sequencing information from 107 patients with HNSCC who underwent CRT. The difference in the NLR between the good response group and the poor response group was significant, with more patients having a high NLR in the poor response group. We also examined the genetic alterations linked to the NLR and found a total of 41 associated genes across eight common pathways searched from the KEGG database. The overall mutation rate was low, and there was no significant mutation difference between the low- and high-NLR groups. Using a multivariate binomial generalized linear model, we identified three candidate genes (MAP2K2, MAP2K4, and ABL1) that showed significant results and were used to create a gene mutation score (GMS). Using the NLR-GMS category, we noticed that the high-NLR-GMS group had significantly shorter relapse-free survival compared to the intermediate- or low-NLR-GMS groups.

10.
Cancer Genomics Proteomics ; 20(6): 582-591, 2023.
Article in English | MEDLINE | ID: mdl-37889057

ABSTRACT

BACKGROUND/AIM: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs. MATERIALS AND METHODS: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses. RESULTS: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel. CONCLUSION: Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/radiotherapy , Cell Line, Tumor , Epigenesis, Genetic , Paclitaxel/therapeutic use , Lymph Nodes/pathology , Methyltransferases/metabolism , Methyltransferases/therapeutic use , Repressor Proteins/metabolism
12.
Biomed Pharmacother ; 163: 114732, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37254289

ABSTRACT

Triple-negative breast cancer (TNBC) is characterized by the loss of expression of several biomarkers, which limits treatment strategies for the disease. In recent years, immunotherapy has shown promising results in the treatment of various tumors. Emerging evidence demonstrated that TNBC is an immune-activated cancer, suggesting that immunotherapy could be a feasible treatment option for TNBC. Cytokine-induced killer (CIK) cell therapy is considered as a potential treatment for cancer treatment. However, it is still not approved as a standard treatment in the clinical setting. Our previous study demonstrated that focal adhesion kinase (FAK) plays important role in regulating the sensitivity of TNBC cells to CIK cells. In this study, we further verify the role of FAK in regulating the immune response in vivo. Our in vitro study indicated that knockdown of FAK in TNBC cells or treat with the FAK inhibitor followed by co-culture with CIK cells induced more cell death than CIK cells treatment only. RNA-seq analysis indicated that suppression of FAK could affect several immune-related gene expressions in TNBC cells that affects the immune response in the tumor microenvironment of TNBC cells. The combination of FAK inhibitor and CIK cells significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone in vivo. Our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment and indicate that the combination of CIK cell therapy with FAK inhibitors may be an alternative therapeutic strategy for patients with TNBC.


Subject(s)
Antineoplastic Agents , Cytokine-Induced Killer Cells , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/metabolism , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Antineoplastic Agents/therapeutic use , Immunotherapy/methods , Immunotherapy, Adoptive , Tumor Microenvironment
13.
Exp Mol Med ; 55(5): 926-938, 2023 05.
Article in English | MEDLINE | ID: mdl-37121970

ABSTRACT

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/therapy , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Chemoradiotherapy , Biomarkers, Tumor/genetics , Mutation , Genomics
14.
Int J Mol Sci ; 24(6)2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36982660

ABSTRACT

The treatment provided for breast cancer depends on the expression of hormone receptors, human epidermal growth factor receptor-2 (HER2), and cancer staging. Surgical intervention, along with chemotherapy or radiation therapy, is the mainstay of treatment. Currently, precision medicine has led to personalized treatment using reliable biomarkers for the heterogeneity of breast cancer. Recent studies have shown that epigenetic modifications contribute to tumorigenesis through alterations in the expression of tumor suppressor genes. Our aim was to investigate the role of epigenetic modifications in genes involved in breast cancer. A total of 486 patients from The Cancer Genome Atlas Pan-cancer BRCA project were enrolled in our study. Hierarchical agglomerative clustering analysis further divided the 31 candidate genes into 2 clusters according to the optimal number. Kaplan-Meier plots showed worse progression-free survival (PFS) in the high-risk group of gene cluster 1 (GC1). In addition, the high-risk group showed worse PFS in GC1 with lymph node invasion, which also presented a trend of better PFS when chemotherapy was combined with radiotherapy than when chemotherapy was administered alone. In conclusion, we developed a novel panel using hierarchical clustering that high-risk groups of GC1 may be promising predictive biomarkers in the clinical treatment of patients with breast cancer.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/therapy , Breast Neoplasms/drug therapy , Chromatin , Chromatin Assembly and Disassembly , Receptor, ErbB-2/metabolism , Chemotherapy, Adjuvant , Kaplan-Meier Estimate , Biomarkers, Tumor/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
15.
Biomedicines ; 11(3)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36979671

ABSTRACT

Head and neck cancers (HNCs) are among the ten leading malignancies worldwide. Despite significant progress in all therapeutic modalities, predictive biomarkers, and targeted therapies for HNCs are limited and the survival rate is unsatisfactory. The importance of telomere maintenance via telomerase reactivation in carcinogenesis has been demonstrated in recent decades. Several mechanisms could activate telomerase reverse transcriptase (TERT), the most common of which is promoter alternation. Two major hotspot TERT promoter mutations (C228T and C250T) have been reported in different malignancies such as melanoma, genitourinary cancers, CNS tumors, hepatocellular carcinoma, thyroid cancers, sarcomas, and HNCs. The frequencies of TERT promoter mutations vary widely across tumors and is quite high in HNCs (11.9-64.7%). These mutations have been reported to be more enriched in oral cavity SCCs and HPV-negative tumors. The association between TERT promoter mutations and poor survival has also been demonstrated. Till now, several therapeutic strategies targeting telomerase have been developed although only a few drugs have been used in clinical trials. Here, we briefly review and summarize our current understanding and evidence of TERT promoter mutations in HNC patients.

16.
Trauma Case Rep ; 44: 100778, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36817071

ABSTRACT

We report an uncommon case of ipsilateral comminuted distal radius and comminuted radial head fractures with posterolateral elbow dislocation. A 51-year-old female had a fall that resulted in a comminuted distal radius fracture with an ipsilateral comminuted radial head fracture and posterolateral dislocation of the elbow. Clinical evaluation revealed that her left elbow was posteriorly dislocated and her left wrist was deformed. Plain radiographs showed an intraarticular fracture of the distal end of the radius and a comminuted radial head fracture with a proximally migrated radius. Magnetic resonance imaging (MRI) also showed lateral ulnar collateral ligament injuries. We addressed her distal radius with an anatomical locking plate and then treated her comminution radial head fracture with a radial head replacement. Postoperative radiographs showed a good reduction. The Cooney score was 90 at one year postoperatively.

18.
Life Sci ; 311(Pt A): 121135, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36349605

ABSTRACT

AIMS: Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most dismal malignancies worldwide. Despite multidisciplinary involvement in interventions involving surgery, radiotherapy, and chemotherapy, most pancreatic cancer patients eventually develop distant metastasis. S-phase kinase-associated protein 2 (Skp2) plays an important role in cell-cycle regulation in pancreatic cancer. However, the role of Skp2 in individualized PDAC treatment is largely unknown. MAIN METHODS: Immunoblotting, quantitative reverse transcription polymerase chain reaction, cell viability test, chromatin immunoprecipitation assay, and xenograft in vivo assay were performed in parental and Skp2-depleted cells. The immunohistochemistry of Skp2 was analyzed on the tissue microarrays of 45 PDAC cases and mice tissues. KEY FINDINGS: In this study, we observed that Skp2 is a marker for poor prognosis in PDAC patients. Upregulation of the inhibitor of κB (IκB)-inducing kinase-nuclear factor kappa B (NF-κB) signal cascade mediated Skp2 expression thereby promoting epithelial-mesenchymal transition (EMT). Depletion of NF-κB-associated signaling effectively prevented Skp2-mediated pancreatic cancer cell migration. As a functional consequence, Skp2 orchestrated with Myc to induce zinc finger E-box binding homeobox 1 (Zeb1) transcription by recruiting p300 to the Zeb1 promoter independent of Skp2 E3-ligase activity. Therefore, blockade of Skp2 could significantly reduce the expression of Zeb1 and inhibit cancer cell migration. In conclusion, Skp2 regulated Zeb1 activity to control the migration and invasion abilities of pancreatic cancer cells. Skp2 expression in PDAC may affect cell vulnerability to standard chemotherapy regimens. SIGNIFICANCE: Therefore, in patients with PDAC, modulation of Skp2 expression could be a novel strategy for preventing cancer cell metastasis.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Mice , Animals , S-Phase Kinase-Associated Proteins/genetics , S-Phase Kinase-Associated Proteins/metabolism , NF-kappa B/metabolism , Cell Line, Tumor , Carcinoma, Pancreatic Ductal/pathology , Pancreatic Neoplasms/pathology , Ubiquitination , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism , Pancreatic Neoplasms
19.
Int J Med Sci ; 19(10): 1615-1627, 2022.
Article in English | MEDLINE | ID: mdl-36185333

ABSTRACT

In recent years, translational research and pharmacological targeting of epigenetic modifications have become the focus of personalized therapy for patients with pancreatic cancer. Preclinical and clinical trials targeting post-translational modifications have been evaluated as monotherapy or in combination with standard chemotherapy. In this study, we selected 43 genes from seven families of chromatin-modifying enzymes and investigated the influences of epigenetic modifications and their interactions on pancreatic ductal adenocarcinoma (PDAC) using hierarchical clustering analysis. Our analysis also evaluated their effects on treatment modalities and regimens of chemotherapy for PDAC. RNA-seq data for a total of 177 patients with pancreatic cancer, obtained from The Cancer Genome Atlas database, were analyzed. Our results suggested that high-risk patients of survival significant chromatin remodeling-associated gene cluster (gene cluster 2), composed of histone methyltransferases, histone acetyltransferases, histone deacetylases, histone demethylases, and 10-11 translocation family, demonstrated inferior progression-free survival and overall survival in patients with PDAC, especially in men. Our novel biomarker, survival significant chromatin remodeling-associated gene cluster, showed superior prediction performance compared with the conventional TNM system. Overall, these findings suggest that epigenetic modifications and interactions play an important role in the prognosis and therapeutic response of patients with PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Chromatin/genetics , Chromatin Assembly and Disassembly/genetics , Cluster Analysis , Histone Acetyltransferases/genetics , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Histone Methyltransferases/genetics , Histones/metabolism , Humans , Male , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Prognosis , Pancreatic Neoplasms
20.
J Pers Med ; 12(3)2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35330508

ABSTRACT

The authors would like to make corrections to a recently published paper [...].

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