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Scientific Reports Jun 2024In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of...
In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10. We propose this method as an effective MRD assay.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm, Residual; Immunophenotyping; Immunoglobulin kappa-Chains; Flow Cytometry; Immunoglobulin lambda-Chains; Female; Male; Immunoglobulin Light Chains
PubMed: 38862612
DOI: 10.1038/s41598-024-64398-6 -
International Journal of General... 2024Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study...
PURPOSE
Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.
PATIENTS AND METHODS
We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.
RESULTS
After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.
CONCLUSION
HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.
PubMed: 38859910
DOI: 10.2147/IJGM.S462844 -
Orthopaedic Surgery Jun 2024It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and... (Review)
Review
OBJECTIVE
It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure.
METHODS
We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed.
RESULTS
All six patients were followed up for 24 to 46 months (mean follow-up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection-related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation.
CONCLUSION
Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long-term disease-free survival with acceptable complications and satisfying neurological function.
PubMed: 38859700
DOI: 10.1111/os.14104 -
Breast Cancer Research : BCR Jun 2024Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune...
BACKGROUND
Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied.
METHODS
Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal-Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC.
RESULTS
There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (T) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response.
CONCLUSIONS
Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + T cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer.
TRIAL REGISTRATION
NCT02022202 . Registered 20 December 2013.
Topics: Humans; Female; Neoadjuvant Therapy; Immunophenotyping; Middle Aged; Breast Neoplasms; Adult; Aged; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Leukocytes, Mononuclear; Biomarkers, Tumor; Prognosis; Lymphocytes, Tumor-Infiltrating; Triple Negative Breast Neoplasms; Prospective Studies; Treatment Outcome; Chemotherapy, Adjuvant
PubMed: 38858721
DOI: 10.1186/s13058-024-01848-z -
International Journal of Implant... Jun 2024Prosthetics for patients after oncological resection of the upper jaw is a complex problem associated with the physiological and anatomical separation of the oral cavity...
PURPOSE
Prosthetics for patients after oncological resection of the upper jaw is a complex problem associated with the physiological and anatomical separation of the oral cavity and the nasal/paranasal region. This study reports the clinical results of the use of the zygomatic implants for prosthetic rehabilitation in patients with maxillectomy due to upper jaw tumors.
MATERIALS AND METHODS
The study included 16 patients who underwent prosthetic rehabilitation using a zygomatic implant after maxillectomy period from 2021 to 2023. After the tumor was removed, immediate surgical obturators were placed. Main prosthetic rehabilitation was performed 6-12 months after tumor removal, but before that, a temporary obturator was made and used. Six-twelve months after tumor resection, 1-4 zygomatic implants were inserted into the zygomatic bone unilaterally or bilaterally. A total of 42 zygomatic implants were installed, 2 of which were unsuccessful and were removed in 1 patient. The implants were placed using the surgical guide, which was planned and prepared digitally.
RESULTS
No postsurgical complications were seen, and the patients were discharged from the hospital after 7-10 days. The patients were able to return to a normal diet (hard food) after just 7 days following surgery, with no further complaints regarding function or pain, apart from the residual edema caused by the intervention.
CONCLUSIONS
The use of prostheses fixed on zygomatic implants in patients with maxillary defects is an effective method of prosthodontic rehabilitation in complex clinical cases after maxillectomy.
Topics: Humans; Zygoma; Male; Female; Maxillary Neoplasms; Middle Aged; Adult; Aged; Dental Implants; Maxilla; Palatal Obturators; Treatment Outcome; Dental Prosthesis, Implant-Supported
PubMed: 38856842
DOI: 10.1186/s40729-024-00545-y -
Biomedicine & Pharmacotherapy =... Jul 2024Multiple myeloma (MM) progression is closely dependent on cells in the bone marrow (BM) microenvironment, including fibroblasts (FBs) and immune cells. In their BM...
Multiple myeloma (MM) progression is closely dependent on cells in the bone marrow (BM) microenvironment, including fibroblasts (FBs) and immune cells. In their BM niche, MM cells adhere to FBs sustaining immune evasion, drug resistance and the undetectable endurance of tumor cells known as minimal residual disease (MRD). Here, we describe the novel bi-specific designed ankyrin repeat protein (DARPin) α-FAPx4-1BB (MP0310) with FAP-dependent 4-1BB agonistic activity. The α-FAPx4-1BB DARPin simultaneously binds to FAP and 4-1BB overexpressed by activated FBs and immune cells, respectively. Although flow cytometry analysis showed that T and NK cells from MM patients were not activated and did not express 4-1BB, stimulation with daratumumab or elotuzumab, monoclonal antibodies (mAbs) currently used for the treatment of MM, significantly upregulated 4-1BB both in vitro and in MM patients following mAb-based therapy. The mAb-induced 4-1BB overexpression allowed the engagement of α-FAPx4-1BB that acted as a bridge between FAPFBs and 4-1BBNK cells. Therefore, α-FAPx4-1BB enhanced both the adhesion of daratumumab-treated NK cells on FBs as well as their activation by improving release of CD107a and perforin, hence MM cell killing via antibody-mediated cell cytotoxicity (ADCC). Interestingly, α-FAPx4-1BB significantly potentiated daratumumab-mediated ADCC in the presence of FBs, suggesting that it may overcome the BM FBs' immunosuppressive effect. Overall, we speculate that treatment with α-FAPx4-1BB may represent a valuable strategy to improve mAb-induced NK cell activity fostering MRD negativity in MM patients through the eradication of latent MRD cells.
Topics: Killer Cells, Natural; Multiple Myeloma; Humans; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Cell Line, Tumor; Tumor Necrosis Factor Receptor Superfamily, Member 9; Membrane Proteins; Endopeptidases
PubMed: 38850654
DOI: 10.1016/j.biopha.2024.116877 -
Aging Jun 2024The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in...
The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in uterine corpus endometrial carcinoma (UCEC) remains unknown. Thus, this study investigated ZDHHC1 expression in UCEC using publicly available TCGA and Xena databases and elucidated the functions and mechanisms of the ZDHHC1 gene in UCEC progression using bioinformatics and experiments. The correlation between ZDHHC1 expression and prognosis, clinical features, immune cells, and RNA modifications of UCEC was evaluated using nomograms, correlation, ROC, and survival analyses. The impacts of ZDHHC1 overexpression on UCEC progression and mechanisms were explored with bioinformatics and experiments. Our study revealed that ZDHHC1 expression was significantly downregulated in UCEC and correlated with poor prognosis, cancer diagnosis, clinical stage, age, weight, body mass index, histological subtypes, residual tumor, tumor grade, and tumor invasion. Notably, Cox regression analysis and constructed nomograms showed that downregulated ZDHHC1 expression was a prognostic factor associated with poor prognosis in patients with UCEC. Conversely, above-normal ZDHHC1 expression inhibited the cell growth, cell cycle transition, migration, and invasion of UCEC cells, which may be related to the cell cycle, DNA replication, PI3K-AKT, and other pathways that promote tumor progression. Altered ZDHHC1 expression in UCEC was significantly associated with RNA modifications and the changes in cancer immune cell populations, such as CD56 bright NK cells, eosinophils, Th2 cells, and cell markers. In conclusion, considerably reduced ZDHHC1 expression in UCEC is associated with cancer cell growth, metastasis, poor prognosis, immune infiltration, and RNA modifications, revealing the promising potential of ZDHHC1 as a prognostic marker for UCEC.
Topics: Humans; Female; Endometrial Neoplasms; Prognosis; Cell Proliferation; Middle Aged; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Neoplasm Metastasis
PubMed: 38848146
DOI: 10.18632/aging.205899 -
Medicine Jun 2024Gamma knife stereotactic radiosurgery (GKRS) is a recognized safe and effective treatment for brain metastasis; however, some complications can present significant... (Review)
Review
RATIONALE
Gamma knife stereotactic radiosurgery (GKRS) is a recognized safe and effective treatment for brain metastasis; however, some complications can present significant clinical challenges. This case report highlights a rare occurrence of cerebrospinal fluid (CSF) leakage and pneumocranium following GKRS, emphasizing the need for awareness and prompt management of these complications.
PATIENT CONCERNS
A 35-year-old male with a history of malignant neoplasm of the lip in 2015 and perineural spread of malignancy into the left cavernous sinus was treated with GKRS in 2017. The patient was admitted emergently 39 days after discharge due to persistent headache and dizziness.
DIAGNOSES
Brain computed tomography (CT) revealed diffuse bilateral pneumocranium alongside an observation of CSF leakage.
INTERVENTIONS
A surgical procedure involving a left frontal-temporal craniotomy was performed to excise a residual skull base tumor and repair the dura, guided by a navigator system. The conclusive pathological assessment revealed the presence of squamous cell carcinoma markers.
OUTCOMES
The patient exhibited excellent tolerance to the entire procedure and experienced a prompt and uneventful recovery process. After surgery, the symptoms alleviated and CSF leak stopped. The follow-up image showed the pneumocranium resolved.
LESSONS
Pneumocranium due to early-stage post-GKRS is uncommon. The rapid tumor shrinkage and timing of brain metastasis spreading through the dura can lead to CSF leak and pneumocranium. We reviewed current treatment options and presented a successful craniotomy-based dura repair case.
Topics: Adult; Humans; Male; Brain Neoplasms; Cerebrospinal Fluid Leak; Pneumocephalus; Postoperative Complications; Radiosurgery; Tomography, X-Ray Computed
PubMed: 38847695
DOI: 10.1097/MD.0000000000038464 -
Medicine Jun 2024To explore the expression and prognostic value of UHRF1 gene in soft tissue sarcoma (STS) and its related molecular mechanism. The expression data and...
To explore the expression and prognostic value of UHRF1 gene in soft tissue sarcoma (STS) and its related molecular mechanism. The expression data and clinicopathological parameters of STS were downloaded from the Cancer Genome Atlas (TCGA). The expression level of UHRF1 in STS and adjacent tissues and its relationship with clinicopathological characteristics were analyzed. The expression level of UHRF1 in STS tissues was significantly higher than that in paracancerous tissues (P < .001), and the overall survival (OS) time of patients with high UHRF1 expression was significantly shorter than that of patients with low UHRF1 expression (P = .002). The expression of UHRF1 was correlated with tumor necrosis, histological type and metastasis, and the differences were statistically significant (P = .013; P = .001; P = .002). The area ratio under receiver operating characteristic (ROC) curve between STS tissue and adjacent tissue of UHRF1 expression was 0.994. Number of tumors (HR = 0.416, 95%CI = 0.260-0.666, P < .001), depth of tumor (HR = 2.888, 95%CI = 0.910-9.168, P = .033), metastasis (HR = 2.888, 95% CI = 1.762-4.732, P < .001), residual tumor (HR = 2.637, 95% CI = 1.721-4.038, P < .001) and UHRF1 expression (HR = 1.342, 95% CI = 1.105-1.630, P = .003) were significantly associated with OS, and high expression of UHRF1 (HR = 1.387, 95%CI = 1.008-1.907, P = .044) was an independent risk factor for the prognosis of STS patients. The results of the nomogram exhibited that UHRF1 expression level had a significant effect on the total score value. GSEA enrichment analysis suggested that UHRF1 was involved in 14 signaling pathways regulating mRNA spliceosome, cell cycle, P53 signaling pathway were identified. Single sample gene set enrichment analysis (ssGSEA) exhibited that the expression of UHRF1 in STS was positively correlated with the level of Th2 cell infiltration, and negatively correlated with plasmacytoid dendritic cells (pDC), natural killer cells (NK), Eosinophils, Mast cells, etc. UHRF1 expression is involved in the immune microenvironment of HCC and affects the occurrence and development of HCC. UHRF1 is highly expressed in STS tissues. It is involved in the regulation of multiple tumor-related signaling pathways and immune cell microenvironment, suggesting that UHRF1 may be a potential molecular marker for prognosis prediction and targeted therapy of STS patients.
Topics: Humans; CCAAT-Enhancer-Binding Proteins; Ubiquitin-Protein Ligases; Sarcoma; Female; Prognosis; Male; Middle Aged; Biomarkers, Tumor; Adult; ROC Curve; Aged; Clinical Relevance
PubMed: 38847665
DOI: 10.1097/MD.0000000000038393 -
Cancer Medicine Jun 2024We have developed explainable machine learning models to predict the overall survival (OS) of retroperitoneal liposarcoma (RLPS) patients. This approach aims to enhance...
OBJECTIVE
We have developed explainable machine learning models to predict the overall survival (OS) of retroperitoneal liposarcoma (RLPS) patients. This approach aims to enhance the explainability and transparency of our modeling results.
METHODS
We collected clinicopathological information of RLPS patients from The Surveillance, Epidemiology, and End Results (SEER) database and allocated them into training and validation sets with a 7:3 ratio. Simultaneously, we obtained an external validation cohort from The First Affiliated Hospital of Naval Medical University (Shanghai, China). We performed LASSO regression and multivariate Cox proportional hazards analysis to identify relevant risk factors, which were then combined to develop six machine learning (ML) models: Cox proportional hazards model (Coxph), random survival forest (RSF), ranger, gradient boosting with component-wise linear models (GBM), decision trees, and boosting trees. The predictive performance of these ML models was evaluated using the concordance index (C-index), the integrated cumulative/dynamic area under the curve (AUC), and the integrated Brier score, as well as the Cox-Snell residual plot. We also used time-dependent variable importance, analysis of partial dependence survival plots, and the generation of aggregated survival SHapley Additive exPlanations (SurvSHAP) plots to provide a global explanation of the optimal model. Additionally, SurvSHAP (t) and survival local interpretable model-agnostic explanations (SurvLIME) plots were used to provide a local explanation of the optimal model.
RESULTS
The final ML models are consisted of six factors: patient's age, gender, marital status, surgical history, as well as tumor's histopathological classification, histological grade, and SEER stage. Our prognostic model exhibits significant discriminative ability, particularly with the ranger model performing optimally. In the training set, validation set, and external validation set, the AUC for 1, 3, and 5 year OS are all above 0.83, and the integrated Brier scores are consistently below 0.15. The explainability analysis of the ranger model also indicates that histological grade, histopathological classification, and age are the most influential factors in predicting OS.
CONCLUSIONS
The ranger ML prognostic model exhibits optimal performance and can be utilized to predict the OS of RLPS patients, offering valuable and crucial references for clinical physicians to make informed decisions in advance.
Topics: Humans; Retroperitoneal Neoplasms; Male; Female; Liposarcoma; Machine Learning; Middle Aged; China; SEER Program; Aged; Risk Factors; Proportional Hazards Models; Prognosis; Adult
PubMed: 38847519
DOI: 10.1002/cam4.7324