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International Journal of Molecular... Jun 2024The association between leukemic stem cells (LSCs) and leukemia development has been widely established in the context of genetic alterations, epigenetic pathways, and... (Review)
Review
The association between leukemic stem cells (LSCs) and leukemia development has been widely established in the context of genetic alterations, epigenetic pathways, and signaling pathway regulation. Hematopoietic stem cells are at the top of the bone marrow hierarchy and can self-renew and progressively generate blood and immune cells. The microenvironment, niche cells, and complex signaling pathways that regulate them acquire genetic mutations and epigenetic alterations due to aging, a chronic inflammatory environment, stress, and cancer, resulting in hematopoietic stem cell dysregulation and the production of abnormal blood and immune cells, leading to hematological malignancies and blood cancer. Cells that acquire these mutations grow at a faster rate than other cells and induce clone expansion. Excessive growth leads to the development of blood cancers. Standard therapy targets blast cells, which proliferate rapidly; however, LSCs that can induce disease recurrence remain after treatment, leading to recurrence and poor prognosis. To overcome these limitations, researchers have focused on the characteristics and signaling systems of LSCs and therapies that target them to block LSCs. This review aims to provide a comprehensive understanding of the types of hematopoietic malignancies, the characteristics of leukemic stem cells that cause them, the mechanisms by which these cells acquire chemotherapy resistance, and the therapies targeting these mechanisms.
Topics: Humans; Hematologic Neoplasms; Neoplastic Stem Cells; Hematopoietic Stem Cells; Leukemia; Signal Transduction; Animals; Tumor Microenvironment; Drug Resistance, Neoplasm; Epigenesis, Genetic; Mutation
PubMed: 38928344
DOI: 10.3390/ijms25126639 -
BMC Cancer Jun 2024Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious...
BACKGROUND
Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions' progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies.
METHODS
Twenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time.
RESULTS
Biplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points.
CONCLUSION
Traditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.
Topics: Animals; Female; Rats; Humans; Tomography, X-Ray Computed; Bone Neoplasms; Breast Neoplasms; Absorptiometry, Photon; Bone Density; Rats, Nude; Paclitaxel; Cell Line, Tumor; Osteolysis; Ibandronic Acid; Bone Density Conservation Agents
PubMed: 38926864
DOI: 10.1186/s12885-024-12374-8 -
Current Oncology (Toronto, Ont.) May 2024The purpose of this study is to compare three commonly used radiotherapy fractionation schedules for bone metastasis in terms of clinical and radiological effectiveness.... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
The purpose of this study is to compare three commonly used radiotherapy fractionation schedules for bone metastasis in terms of clinical and radiological effectiveness. A total of 93 patients with osteolytic bone metastasis were randomized to receive 8 Gyin a single fraction (group A), 20 Gy in 5 fractions (group B) and 30 Gy in 10 fractions (group C). Changes in bone density were measured using the Relative Electron Density (RED) type corrected by Thomas (pe = HU/1.950 + 1.0), where HU is Hounsfield Units. Pain response was assessed according to the Brief Pain Inventory tool. Quality of life was estimated using the EORTC QLQ-C30 and the MD Anderson Symptom (MDAS) tools.After RT, RED, together with the parameters of EORTC QLQ-C30, MDAS and SAT, significantly increased in all groups ( < 0.001).Specifically, the increase of RED was higher in group C compared to group Athree months post-RT ( = 0.014). Group C was also superior to group A in terms of QoL and BPI three months post-treatment. Multifractionated radiotherapy for osteolytic bone metastasis is superior to single fraction radiotherapy in terms of improvement in quality of life and bone remineralization three months post-RT.
Topics: Humans; Bone Neoplasms; Dose Fractionation, Radiation; Female; Male; Middle Aged; Quality of Life; Aged; Osteolysis; Adult; Bone Density; Treatment Outcome
PubMed: 38920717
DOI: 10.3390/curroncol31060233 -
Asian Spine Journal Jun 2024Retrospective study.
Correlation between the maximum standard uptake value and mean Hounsfield unit on single-photon emission computed tomography-computed tomography to discriminate benign and metastatic lesions among patients with breast cancer.
STUDY DESIGN
Retrospective study.
PURPOSE
To compare and correlate technetium-99m methylene diphosphonate uptake between benign and metastatic bone lesions using semiquantitative analysis of maximum standard uptake value (SUVmax) and mean Hounsfield unit (HU) in single-photon emission computed tomography-computed tomography (SPECT-CT).
OVERVIEW OF LITERATURE
Qualitative interpretation of metastatic bone lesions in breast cancer on bone scintigraphy is often complicated by coexisting benign lesions.
METHODS
In total, 185 lesions were identified on bone and SPECT-CT scans from 32 patients. Lesions were classified as metastatic (109 sclerotic lesions) and benign (76 lesions) morphologically on low-dose CT. Semiquantitative analysis using SUVmax and mean HU was performed on the lesions and compared. To discriminate benign and metastatic lesions, the correlation between SUVmax and mean HU was determined using the intraclass correlation coefficients.
RESULTS
The SUVmax was higher in metastatic lesions (20.66±14.36) but lower in benign lesions (10.18±12.79) (p<0.001). The mean HU was lower in metastatic lesions (166.62±202.02) but higher in benign lesions (517.65±192.8) (p<0.001). A weak negative correlation was found between the SUVmax and the mean HU for benign lesions, and a weak positive correlation was noted between the SUVmax and the mean HU on malignant lesions with no statistical significance (p=0.394 and 0.312, respectively). The cutoff values obtained were 10.8 for SUVmax (82.6% sensitivity and 84.2% specificity) and 240.86 for the mean HU (98.7% sensitivity and 88.1% specificity) in differentiating benign from malignant bone lesions.
CONCLUSIONS
Semiquantitative assessment using SUVmax and HU can complement qualitative analysis. Metastatic lesions had higher SUVmax but lower mean HU than benign lesions, whereas benign lesions demonstrated higher mean HU but lower SUVmax. A weak correlation was found between the SUVmax and the mean HU on malignant and benign lesions. Cutoff values of 10.8 for the SUVmax and 240.86 for the mean HU may differentiate bone metastases from benign lesions.
PubMed: 38917860
DOI: 10.31616/asj.2022.0451 -
JCO Clinical Cancer Informatics Jun 2024The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy...
PURPOSE
The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis.
MATERIALS AND METHODS
Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed.
RESULTS
The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids.
CONCLUSION
An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection.
Topics: Humans; Machine Learning; Bone Neoplasms; Palliative Care; Male; Female; Prognosis; Aged; Middle Aged; Algorithms
PubMed: 38917384
DOI: 10.1200/CCI.24.00027 -
Journal of Cardiothoracic Surgery Jun 2024First rib tumors are extremely rare. Its compression of neurovascularity can easily lead to severe complications such as thoracic outlet syndrome, so early surgical... (Review)
Review
BACKGROUND
First rib tumors are extremely rare. Its compression of neurovascularity can easily lead to severe complications such as thoracic outlet syndrome, so early surgical resection is crucial. However, there is no standardized approach to surgery.
CASE PRESENTATION
A previously healthy 18-year-old Chinese male undergoes a chest computed tomography (CT) scan that incidentally reveals a raised calcified mass on the right first rib, which is most likely an osteochondroma when combined with magnetic resonance imaging (MRI). We achieved excellent results with resection and thoracic reconstruction by adopting an inverse L-shaped incision in the anterior chest and a longitudinal split of the sternum.
CONCLUSIONS
Our practice provides great reference for the surgical management of first rib tumors.
Topics: Humans; Male; Ribs; Osteochondroma; Adolescent; Bone Neoplasms; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Manubrium
PubMed: 38915107
DOI: 10.1186/s13019-024-02902-9 -
World Journal of Surgical Oncology Jun 2024Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave...
AIM
Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave ablation (MWA) assisted degradation therapy in the surgical treatment of intramedullary chondrosarcoma of the extremities, to provide a new reference and research basis for the surgical treatment of CS.
METHODS
We recruited 36 patients with intramedullary CS who underwent MWA assisted extended curettage. Preoperative patient demographics and clinical data were recorded. Surgery was independently assisted by a medical team. Patients were followed up strictly and evaluated for oncological prognosis, radiological results, limb joint function, pain, and complications.
RESULTS
We included 15 men and 21 women (mean age: 43.5 ± 10.1). The average length of the lesion was 8.1 ± 2.5 cm. Based on preoperative radiographic, clinical manifestations, and pathological results of puncture biopsy, 28 patients were preliminarily diagnosed with CS-grade I and eight patients with CS-grade II. No recurrence or metastasis occurred in the postoperative follow-up. The average Musculoskeletal Tumor Society score was 28.8 ± 1.0, significantly better than presurgery. Secondary shoulder periarthritis and abduction dysfunction occurred in early postoperative stage CS of the proximal humerus in some, but returned to normal after rehabilitation exercise. Secondary bursitis occurred at the knee joint in some due to the internal fixation device used in treatment; however, secondary osteoarthritis and avascular necrosis of the femoral head were not observed. Overall, oncological and functional prognoses were satisfactory.
CONCLUSIONS
The application of MWA assisted degradation therapy in intramedullary CS can achieve satisfactory oncology and functional prognosis, providing a new option for the limited treatment of CS.
Topics: Humans; Male; Female; Chondrosarcoma; Adult; Bone Neoplasms; Microwaves; Middle Aged; Follow-Up Studies; Prognosis; Extremities; Curettage; Ablation Techniques
PubMed: 38914990
DOI: 10.1186/s12957-024-03443-0 -
BMC Cancer Jun 2024Nowadays, different therapeutic options are available for the first-line treatment of metastatic renal cell carcinoma (mRCC). Immuno-combinations are the standard... (Observational Study)
Observational Study
BACKGROUND
Nowadays, different therapeutic options are available for the first-line treatment of metastatic renal cell carcinoma (mRCC). Immuno-combinations are the standard first-line therapy in all mRCC patients regardless of the International Metastatic RCC Database Consortium (IMDC) risk category, even though TKI monotherapy is still a therapeutic option in selected patients. However, comparisons between the different first-line treatment strategies are lacking and few real-world data are available in this setting. For this reason, the regimen choice represents an important issue in clinical practice and the optimal treatment sequence remains unclear.
METHODS
The REGAL study is a multicentric prospective observational study enrolling mRCC patients treated with first-line systemic therapy according to clinical practice in a real-world setting. A retrospective cohort of mRCC patients who received first-line systemic therapy from the 1st of January 2021 will also be included. The primary objective is to identify potential prognostic and predictive factors that could help guide the treatment choice; secondary objectives included the assessment of the prognostic performance of the novel prognostic Meet-URO score (IMDC score + neutrophil-to-lymphocyte ratio + bone metastases) compared with the IMDC score and the comparison between treatment strategies according to response and survival outcomes and toxicity profile.
DISCUSSION
Considering the high number of therapeutic first-line strategies available for mRCC, the identification of clinical prognostic and predictive factors to candidate patients to a preferable systemic therapy is still an unmet clinical need. The Meet-URO 33 study aims to provide a large-scale real-world database on mRCC patients, to identify the clinical predictive and prognostic factors and the different performances between the ICI-based combinations according to response, survival and toxicity.
TRIAL REGISTRATION
CESC IOV 2023-78.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Registries; Prospective Studies; Prognosis; Male; Female; Retrospective Studies; Middle Aged; Aged
PubMed: 38914928
DOI: 10.1186/s12885-024-12319-1 -
Scientific Reports Jun 2024This study aimed to establish a machine learning (ML) model for predicting hepatic metastasis in esophageal cancer. We retrospectively analyzed patients with esophageal...
This study aimed to establish a machine learning (ML) model for predicting hepatic metastasis in esophageal cancer. We retrospectively analyzed patients with esophageal cancer recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2020. We identified 11 indicators associated with the risk of liver metastasis through univariate and multivariate logistic regression. Subsequently, these indicators were incorporated into six ML classifiers to build corresponding predictive models. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. A total of 17,800 patients diagnosed with esophageal cancer were included in this study. Age, primary site, histology, tumor grade, T stage, N stage, surgical intervention, radiotherapy, chemotherapy, bone metastasis, and lung metastasis were independent risk factors for hepatic metastasis in esophageal cancer patients. Among the six models developed, the ML model constructed using the GBM algorithm exhibited the highest performance during internal validation of the dataset, with AUC, accuracy, sensitivity, and specificity of 0.885, 0.868, 0.667, and 0.888, respectively. Based on the GBM algorithm, we developed an accessible web-based prediction tool (accessible at https://project2-dngisws9d7xkygjcvnue8u.streamlit.app/ ) for predicting the risk of hepatic metastasis in esophageal cancer.
Topics: Humans; Machine Learning; Esophageal Neoplasms; Liver Neoplasms; Male; Female; Middle Aged; Aged; Retrospective Studies; Risk Factors; ROC Curve; SEER Program
PubMed: 38914571
DOI: 10.1038/s41598-024-63213-6 -
Cureus May 2024Appendicitis is a common surgical emergency marked by inflammation of the appendix, often due to blockage of the appendix lumen by fecoliths, lymphoid hyperplasia, or...
Appendicitis is a common surgical emergency marked by inflammation of the appendix, often due to blockage of the appendix lumen by fecoliths, lymphoid hyperplasia, or neoplasms. While various causes are known, appendicitis triggered by a foreign body (FB) is exceptionally rare. This case report highlights a rare presentation of appendicitis in a 32-year-old male with no significant medical history, who presented with acute lower right abdominal pain, fever, and vomiting. Initial evaluation suggested appendicitis, further supported by laboratory findings and diagnostic imaging revealing a retrocecal appendix with surrounding inflammation. Remarkably, an FB, a fish bone, was discovered lodged within the perforated appendix, elucidating the unusual etiology. Emergency laparotomy confirmed the diagnosis and facilitated prompt surgical intervention. This case underscores the importance of thorough evaluation and consideration of uncommon causes in patients presenting with acute abdominal pain, illustrating the critical role of detailed history-taking and clinical acumen in guiding management decisions and ensuring favorable patient outcomes.
PubMed: 38910666
DOI: 10.7759/cureus.60910