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Frontiers in Immunology 2024Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other... (Review)
Review
Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.
Topics: Female; Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Mixed Connective Tissue Disease; Ovarian Neoplasms; Purpura, Thrombocytopenic, Idiopathic
PubMed: 38903494
DOI: 10.3389/fimmu.2024.1382964 -
The Journal of International Medical... Jun 2024Bizarre parosteal osteochondromatous proliferation (BPOP), also termed Nora lesion, is a rare, benign tumor most often located in the hands and feet. We herein present...
Bizarre parosteal osteochondromatous proliferation (BPOP), also termed Nora lesion, is a rare, benign tumor most often located in the hands and feet. We herein present the second reported case of BPOP affecting the spine, an uncommon location. One year after surgical excision, the patient was pain-free and showed no evidence of recurrence. We reviewed a total of 323 cases of BPOP among 101 articles, providing the first systematic update on the latest knowledge of BPOP. The age of patients with BPOP ranges from 3 months to 87 years, peaking in the second and third decades of life. The hands are the most common location of BPOP (58.39%), followed by the feet (20.81%). Imaging features play a key role in the diagnosis of BPOP, but histopathologic diagnosis remains the gold standard. Differential diagnosis of BPOP should be based on the epidemiologic and clinical features as well as clinical examination findings. Surgical resection is the most extensively used treatment for BPOP. Recurrence is common (37.44%) and can be treated with re-excision. This article can deepen our understanding of BPOP and will be helpful for the diagnosis and treatment of BPOP in clinical practice.
Topics: Humans; Osteochondroma; Male; Female; Adult; Spinal Neoplasms; Magnetic Resonance Imaging; Middle Aged; Diagnosis, Differential
PubMed: 38901838
DOI: 10.1177/03000605241259752 -
World Journal of Clinical Cases Jun 2024Paragangliomas (PG) are rare neoplasms of neuroendocrine origin that tend to be highly vascularized, slow-growing, and usually sporadic. To date, common treatment...
BACKGROUND
Paragangliomas (PG) are rare neoplasms of neuroendocrine origin that tend to be highly vascularized, slow-growing, and usually sporadic. To date, common treatment options are surgical resection (SR), with or without radiation therapy (RT), and a watch-and-wait approach.
AIM
To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT (FSRT) treatment in unresectable PG (uPG).
METHODS
We retrospectively evaluated patients with uPG (medically inoperable or refused SR) treated with FSRT with a Cyberknife System (Accuray Incorporated, Sunnyvale, California). Toxicity and initial efficacy were evaluated.
RESULTS
From May 2009 to January 2023, 6 patients with a median age of 68 (range 20-84) were treated with FSRT. The median delivered dose was 21 Gy (range 20-30 Gy) at a median isodose line of 75.5% (range 70%-76%) in 4 fractions (range 3-5 fractions). The median volume was 13.6 mL (range 12.4-65.24 mL). The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively. Site of origin involved were the timpa-nojugular glomus (4/6), temporal bone, and cervical spine. In 1 of the 6 patients, the follow-up was insufficient; 5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%. We observed negligible toxicities during and after RT. The majority of patients showed stable symptoms during follow-up. Only 1 patient developed spine metastases.
CONCLUSION
Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR.
PubMed: 38899289
DOI: 10.12998/wjcc.v12.i16.2729 -
Frontiers in Endocrinology 2024While bone metastases (BMs) are present in a minority of thyroid cancer (TC) patients at the time of initial diagnosis, there has been growing concern regarding their...
OBJECTIVE
While bone metastases (BMs) are present in a minority of thyroid cancer (TC) patients at the time of initial diagnosis, there has been growing concern regarding their impact on life expectancy and quality of life. The aim of this study was to identify prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) in these patients and provide therapeutic recommendations based on the findings.
METHODS
In this retrospective cohort study, we included 82 patients diagnosed as TC with BM received treatment in our department from 2011.03 to 2023.03 (average follow-up duration was 3.02 years). The retrospective study was performed according to the inclusion and exclusion criteria. Kaplan-Meier analysis was used to estimate the OS and CSS, while the univariate and multivariate Cox proportional hazard models were employed to determine prognostic factors associated with OS and CSS. Also, 287 patients' data were collected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 to confirm the prognostic factors identified in the retrospective study.
RESULTS
The average survival time of the 82 patients was estimated to be 5.818 years (with a 95% confidence interval (CI) of 4.767 to 6.868 years). The cox regression analysis showed that older age (hazard ratio (HR) = 1.045, 95% CI: 1.001-1.092, P = 0.047), larger tumor size (>5cm, HR = 11.087, 95% CI: 3.728 - 32.976, P = 0.000), and the presence of extraosseous metastasis (HR = 3.247, 95% CI: 1.376 - 7.665, P = 0.007) were statistically significant factors associated with worse CSS. The results were furtherly confirmed in 287 SEER-sourced patients (age (HR = 1.020, 95% CI: 1.006 - 1.034, P = 0.006), tumor size (HR = 2.917, 95% CI: 2.044 - 4.161, P = 0.000), and extraosseous metastasis (HR = 3.726, 95% CI: 2.571 - 5.398, P = 0.000)).
CONCLUSIONS
These results offer a population-based assessment of prognostic factors for patients with TC and BMs, revealing that age, primary tumor size (>5cm), and presence of extraosseous metastases are independent prognostic factors that correlate with worse survival. Accordingly, treatment for such patients ought to concentrate on systemic integrative therapy instead of surgical intervention.
Topics: Humans; Thyroid Neoplasms; Male; Bone Neoplasms; Female; Retrospective Studies; Prognosis; Middle Aged; Adult; Aged; Survival Rate; Follow-Up Studies; Kaplan-Meier Estimate; SEER Program; Young Adult
PubMed: 38899008
DOI: 10.3389/fendo.2024.1344795 -
BMC Cancer Jun 2024The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide...
BACKGROUND
The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting.
PATIENTS AND METHODS
The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5.
RESULTS
The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities.
CONCLUSIONS
14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.
Topics: Humans; Ifosfamide; Male; Female; Retrospective Studies; Osteosarcoma; Adult; Adolescent; Young Adult; Bone Neoplasms; Neoplasm Recurrence, Local; Middle Aged; Child; Antineoplastic Agents, Alkylating; Neoplasm Grading; Treatment Outcome
PubMed: 38898388
DOI: 10.1186/s12885-024-12498-x -
Sensors (Basel, Switzerland) May 2024Adherent cells perceive mechanical feedback from the underlying matrix and convert it into biochemical signals through a process known as mechanotransduction. The...
Adherent cells perceive mechanical feedback from the underlying matrix and convert it into biochemical signals through a process known as mechanotransduction. The response to changes in the microenvironment relies on the cell's mechanical properties, including elasticity, which was recently identified as a biomarker for various diseases. Here, we propose the design, development, and characterization of a new system for the measurement of adherent cells' , a parameter correlated with cells' elasticity. To consider the interplay between adherent cells and the host extracellular matrix, cell stretching was combined with adhesion on substrates with different stiffnesses. The technique is based on the linear stretching of silicone chambers, high-speed image acquisition, and feedback for image centering. The system was characterized in terms of the strain homogeneity, impact of collagen coating, centering capability, and sensitivity. Subsequently, it was employed to measure the of two osteosarcoma cell lines, low-aggressive osteoblast-like SaOS-2 and high-aggressive 143B, cultured on two different substrates to recall the stiffness of the bone and lung extracellular matrices. Results demonstrated good substrate homogeneity, a negligible effect of the collagen coating, and an accurate image centering. Finally, the experimental results showed an average that was lower in the 143B cells in comparison with the SaOS-2 cells in all the tested conditions.
Topics: Osteosarcoma; Humans; Cell Line, Tumor; Extracellular Matrix; Mechanotransduction, Cellular; Cell Adhesion; Elasticity; Stress, Mechanical; Bone Neoplasms; Collagen; Osteoblasts
PubMed: 38894171
DOI: 10.3390/s24113383 -
Cancers May 2024Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic...
Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms. We aimed to identify overlapping mechanisms in MSCs derived from myeloid and lymphoid neoplasms contributing to disease progression and suppression of HSPCs to develop interventions that target these mechanisms. MSCs derived from healthy donors ( = 44) and patients diagnosed with myeloproliferative neoplasia ( = 11), myelodysplastic syndromes ( = 16), or acute myeloid leukemia ( = 25) and B-Non-Hodgkin lymphoma ( = 9) with BM infiltration and acute lymphoblastic leukemia ( = 9) were analyzed for their functionality and by RNA sequencing. A reduced growth and differentiation capacity of MSCs was found in all entities. RNA sequencing distinguished both groups but clearly showed overlapping differentially expressed genes, including major players in the BMP/TGF and WNT-signaling pathway which are crucial for growth, osteogenesis, and hematopoiesis. Functional alterations in healthy MSCs were inducible by exposure to supernatants from malignant cells, implicating the involvement of these factors in disease progression. Overall, we were able to identify overlapping factors that pose potential future therapeutic targets.
PubMed: 38893194
DOI: 10.3390/cancers16112071 -
Journal of Clinical Medicine Jun 2024Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the...
Translation, Cultural Adaptation, and Validation into Romanian of the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS or MPN-10) Questionnaire.
Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10), was developed. We conducted the translation, cultural adaptation, and validation into Romanian of the MPN-10. We translated the MPN-10 and tested its psychometric properties. We recruited 180 MPN patients: 66 polycythemia vera (36.67%), 61 essential thrombocythemia (33.89%), 51 primary and secondary myelofibrosis (SMF) (28.33%), and 2 MPN-unclassifiable (1.11%). The mean TSS was 19.51 ± 16.51 points. Fatigue, inactivity, and concentration problems were the most cumbersome symptoms. We detected scoring differences between MPN subtypes regarding weight loss ( < 0.001), fatigue ( = 0.006), early satiety ( = 0.007), night sweats ( = 0.047), pruritus ( = 0.05), and TSS ( = 0.021). There were strong positive associations between TSS and inactivity, fatigue, and concentration problems, and moderate negative correlations between QoL scores and all MPN-10 items. Cronbach's α internal consistency coefficient was 0.855. The Kaiser-Meyer-Olkin construct validity test result was 0.870 and the Bartlett Sphericity Test was significant ( < 0.001). Symptom scores were loaded into one single factor according to the exploratory factor analysis. The Romanian MPN-10 version displayed excellent psychometric properties and is a reliable instrument for assessing symptom burden and QoL in Romanian MPN patients.
PubMed: 38892995
DOI: 10.3390/jcm13113284 -
International Journal of Molecular... Jun 2024Acute Erythroid Leukemia (AEL) is a rare and aggressive subtype of Acute Myeloid Leukemia (AML). In 2022, the World Health Organization (WHO) defined AEL as a biopsy... (Review)
Review
Acute Erythroid Leukemia (AEL) is a rare and aggressive subtype of Acute Myeloid Leukemia (AML). In 2022, the World Health Organization (WHO) defined AEL as a biopsy with ≥30% proerythroblasts and erythroid precursors that account for ≥80% of cellularity. The International Consensus Classification refers to this neoplasm as "AML with mutated ". Classification entails ≥20% blasts in blood or bone marrow biopsy and a somatic mutation (VAF > 10%). This type of leukemia is typically associated with biallelic mutations and a complex karyotype, specifically 5q and 7q deletions. Transgenic mouse models have implicated several molecules in the pathogenesis of AEL, including transcriptional master regulator GATA1 (involved in erythroid differentiation), master oncogenes, and CDX4. Recent studies have also characterized AEL by epigenetic regulator mutations and transcriptome subgroups. AEL patients have overall poor clinical outcomes, mostly related to their poor response to the standard therapies, which include hypomethylating agents and intensive chemotherapy. Allogeneic bone marrow transplantation (AlloBMT) is the only potentially curative approach but requires deep remission, which is very challenging for these patients. Age, AlloBMT, and a history of antecedent myeloid neoplasms further affect the outcomes of these patients. In this review, we will summarize the diagnostic criteria of AEL, review the current insights into the biology of AEL, and describe the treatment options and outcomes of patients with this disease.
Topics: Humans; Leukemia, Erythroblastic, Acute; Animals; Mutation; Tumor Suppressor Protein p53
PubMed: 38892446
DOI: 10.3390/ijms25116256 -
International Journal of Molecular... Jun 2024In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the...
In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G/M arrest. The expression of the G/M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection.
Topics: Humans; DNA-Activated Protein Kinase; Cell Line, Tumor; Chondrosarcoma; Heavy Ion Radiotherapy; Telomere; Cell Cycle Checkpoints; DNA Repair; Radiation Tolerance; Pyrazoles; Cell Proliferation; Bone Neoplasms; G2 Phase Cell Cycle Checkpoints
PubMed: 38892366
DOI: 10.3390/ijms25116179