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Journal of Radiology Case Reports 2024Intervertebral disc herniation, defined as the protrusion or extrusion of the disc mass outside the disc space, is common and easy to diagnose on conventional Magnetic... (Review)
Review
BACKGROUND
Intervertebral disc herniation, defined as the protrusion or extrusion of the disc mass outside the disc space, is common and easy to diagnose on conventional Magnetic Resonance imaging (MRI) or Computed Tomography (CT) scans. However, the sequestrated disc fragments are challenging to detect, and intervertebral disc mass displacement into the dural sac, which can lead to serious neurological problems such as Cauda equina syndrome (CES). The sequestrated disc fragments do not have specific clinical or radiological characteristics that can differentiate an atypical disc mass from a tumor, making the diagnosis difficult preoperatively. Herein, we describe the use of Sampling Perfection with Application Optimized Contrast using different flip angle Evolution in Magnetic Resonance Imaging (3D SPACE MRI) in the diagnosis of the intervertebral disc fragment that mimicked a tumor.
CASE PRESENTATION
In this study, we report two cases of sequestered lumbar disc herniation. The first case was a 37-year-old patient with a 2-year history of intermittent left lower limb pain that aggravates with exercise and is relieved at rest, while the second case was a 42-year-old patient with a history of 40 days of numbness and pain in the left lower limb.
CONCLUSION
3D SPACE MRI is a beneficial diagnostic imaging tool for discriminating between disc mass that mimics a tumor and a tumor before surgery. If the disc fragment mimicking a tumor can be identified before the operation, open surgical treatment won't be necessary for all patients.
Topics: Humans; Intervertebral Disc Displacement; Magnetic Resonance Imaging; Diagnosis, Differential; Adult; Lumbar Vertebrae; Imaging, Three-Dimensional; Male; Female; Spinal Neoplasms
PubMed: 38910587
DOI: 10.3941/jrcr.v18i1.5195 -
Signal Transduction and Targeted Therapy Jun 2024Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for it. The tumor microenvironment...
Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for it. The tumor microenvironment (TME) in pancreatic cancer, distinguished by fibrosis and the existence of cancer-associated fibroblasts (CAFs), exerts a pivotal influence on both tumor advancement and resistance to therapy. Recent advancements in the field of engineered extracellular vesicles (EVs) offer novel avenues for targeted therapy in pancreatic cancer. This study aimed to develop engineered EVs for the targeted reprogramming of CAFs and modulating the TME in pancreatic cancer. EVs obtained from bone marrow mesenchymal stem cells (BMSCs) were loaded with miR-138-5p and the anti-fibrotic agent pirfenidone (PFD) and subjected to surface modification with integrin α5-targeting peptides (named IEVs-PFD/138) to reprogram CAFs and suppress their pro-tumorigenic effects. Integrin α5-targeting peptide modification enhanced the CAF-targeting ability of EVs. miR-138-5p directly inhibited the formation of the FERMT2-TGFBR1 complex, inhibiting TGF-β signaling pathway activation. In addition, miR-138-5p inhibited proline-mediated collagen synthesis by directly targeting the FERMT2-PYCR1 complex. The combination of miR-138-5p and PFD in EVs synergistically promoted CAF reprogramming and suppressed the pro-cancer effects of CAFs. Preclinical experiments using the orthotopic stroma-rich and patient-derived xenograft mouse models yielded promising results. In particular, IEVs-PFD/138 effectively reprogrammed CAFs and remodeled TME, which resulted in decreased tumor pressure, enhanced gemcitabine perfusion, tumor hypoxia amelioration, and greater sensitivity of cancer cells to chemotherapy. Thus, the strategy developed in this study can improve chemotherapy outcomes. Utilizing IEVs-PFD/138 as a targeted therapeutic agent to modulate CAFs and the TME represents a promising therapeutic approach for pancreatic cancer.
Topics: Pancreatic Neoplasms; Extracellular Vesicles; Humans; Cancer-Associated Fibroblasts; Mice; MicroRNAs; Animals; Tumor Microenvironment; Cellular Reprogramming; Cell Line, Tumor; Mesenchymal Stem Cells; Neoplasm Proteins; Gemcitabine
PubMed: 38910148
DOI: 10.1038/s41392-024-01872-7 -
World Journal of Surgical Oncology Jun 2024Sinonasal malignant tumors are a group of uncommon malignancies that account for less than 1% of all tumors. These tumors often involve the maxillary sinus and nasal...
Sinonasal malignant tumors are a group of uncommon malignancies that account for less than 1% of all tumors. These tumors often involve the maxillary sinus and nasal cavity, with less cumulative incidence in the ethmoidal sinus, sphenoidal sinus, and frontal sinus. The lack of consensus on the management of sinonasal malignancies is due to their rarity, diagnostic challenges, and the heterogeneity of treatments. In this paper, we present a case of endoscopic-assisted medial canthus incision combined with radiotherapy in the treatment of sinonasal malignant tumors, with the aim of providing valuable insights to clinicians on the management of these tumors.
Topics: Humans; Esthesioneuroblastoma, Olfactory; Endoscopy; Nose Neoplasms; Nasal Cavity; Prognosis; Male; Middle Aged; Female; Paranasal Sinus Neoplasms
PubMed: 38909260
DOI: 10.1186/s12957-024-03448-9 -
Journal of Medical Case Reports Jun 2024Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, representing less than 1% of all lung tumors. The two most common among them are adenoid cystic...
BACKGROUND
Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, representing less than 1% of all lung tumors. The two most common among them are adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Very few cases are reported in literature. We report a similar rare case of salivary gland type lung carcinoma that presented for the first time with unilateral opacification of left hemithorax.
CASE PRESENTATION
A 38-year-old man of North Indian origin, who was a a nonsmoker, presented with complaints of shortness of breath and cough for 1 year, which has increased in the last 2 months and was associated with significant weight loss. A frontal radiograph of the chest and computed tomography of the chest were performed, which showed a mass in the left upper lobe of the lung with its epicenter in the left main bronchus. A bronchoscopic guided biopsy was performed, and histopathology confirmed the diagnosis of lung carcinoma of salivary gland type (adenoid cystic carcinoma). There was invasion of major vessels, hence the patient was offered and started on palliative management instead of surgical treatment. In spite of palliative management of two cycles of chemotherapy and radiotherapy, the patient succumbed to the disease within 2 months from the time of diagnosis.
CONCLUSION
Lung carcinoma of the salivary gland type (especially adenoid cystic carcinoma) usually presents at a later stage. The resectability of the tumor depends on the involvement of the surrounding major vessels. Interestingly, these cancers have no association with smoking. The prognosis depends on the extent of the disease at the time of diagnosis. Hence, imaging plays a major role in deciding the further plan of management.
Topics: Humans; Male; Adult; Lung Neoplasms; Tomography, X-Ray Computed; Carcinoma, Adenoid Cystic; Liver Neoplasms; Fatal Outcome; Bone Neoplasms; Palliative Care
PubMed: 38909203
DOI: 10.1186/s13256-024-04607-y -
BMC Oral Health Jun 2024Neurofibroma is a common benign tumor of neuronal origin that can occur as a solitary tumor or as a component of the generalized syndrome of neurofibromatosis....
BACKGROUND
Neurofibroma is a common benign tumor of neuronal origin that can occur as a solitary tumor or as a component of the generalized syndrome of neurofibromatosis. Neurofibromas are primarily located in the subcutaneous soft tissues and commonly involve extra-oral sites. Solitary intraosseous neurofibromas of the oral cavity are infrequent, with occurrences in the maxilla being exceedingly rare.
CASE PRESENTATION
A 22-year-old male patient presented with an asymptomatic mass in the maxilla. Cone-beam computed tomography revealed a round, well-outlined, radiolucent lesion with expansive growth. The neoplasm with the complete capsule was completely removed and confirmed as a neurofibroma based on histopathological and immunohistochemical findings. The reported cases of solitary intraosseous neurofibromas located in the maxilla published in the English literature were compiled to assist in the diagnosis of solitary intraosseous neurofibromas of the maxilla. Nine months after the surgery, there were no signs of tumor recurrence or malignant transformation.
CONCLUSIONS
This report emphasizes that rare locations of neurofibromas, such as solitary intraosseous neurofibromas in the maxilla, typically demonstrate nonspecific clinical and radiological features. Clinicians should consider solitary intraosseous neurofibromas as possible differential diagnoses and recognize the histopathological and immunohistochemical features to confirm the correct diagnosis. A longer follow-up period is required because of the potential for local recurrence and malignant transformation of these tumors.
Topics: Humans; Male; Neurofibroma; Maxillary Neoplasms; Young Adult; Cone-Beam Computed Tomography; Diagnosis, Differential
PubMed: 38909194
DOI: 10.1186/s12903-024-04470-9 -
Journal For Immunotherapy of Cancer Jun 2024Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor...
Circulating receptor activator of nuclear factor kappa-B ligand (RANKL) levels predict response to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC).
BACKGROUND
Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment and immune cell responses. This study aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy.
METHODS
Plasma RANKL levels were measured in 100 patients with advanced NSCLC without bone metastases undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. To establish the optimal cut-off value, we used the Cutoff Finder package in R. Survival curves for four distinct patient groups, according to their RANKL and PDL1 levels (high or low), were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS).
RESULTS
The optimal RANKL cut-off was established at 280.4 pg/mL, categorizing patients into groups with high or low RANKL levels. A significant association was observed between increased RANKL concentrations and decreased survival rates at 24 months, only within the subgroup expressing high levels of PDL1 (p=0.002). Additionally, low RANKL levels in conjunction with elevated PDL1 expression correlated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, p=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, p=0.003), indicating RANKL's potential as an indicator of adverse prognosis in these patients. Multivariate analysis identified RANKL as an independent negative prognostic factor for both PFS and OS, regardless of other clinicopathological features.
CONCLUSION
These results highlight the prognostic and predictive value of RANKL specifically in patients with high PDL1 expression.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Male; Female; RANK Ligand; Lung Neoplasms; Immune Checkpoint Inhibitors; Aged; Middle Aged; Aged, 80 and over; Adult; B7-H1 Antigen; Biomarkers, Tumor; Prognosis
PubMed: 38908859
DOI: 10.1136/jitc-2024-009432 -
Journal of Nanobiotechnology Jun 2024Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by...
Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs' function by CE-sEVs.
Topics: Osteosarcoma; Extracellular Vesicles; Lung Neoplasms; Animals; Humans; Mice; Cell Line, Tumor; Bone Neoplasms; Cancer-Associated Fibroblasts; Mice, Inbred BALB C; Saponins; Mice, Nude; Cell Movement; Lung
PubMed: 38907233
DOI: 10.1186/s12951-024-02636-9 -
BMC Cancer Jun 2024The role of hemoglobin (HGB) in common malignant tumors remains unclear.
BACKGROUND
The role of hemoglobin (HGB) in common malignant tumors remains unclear.
METHODS
A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve.
RESULTS
High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05).
CONCLUSION
High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.
Topics: Humans; Retrospective Studies; Male; Female; Hemoglobins; Neoplasms; Genome-Wide Association Study; Prognosis; Middle Aged; Mendelian Randomization Analysis; Risk Factors; Nutrition Surveys; Adult; Aged; Biomarkers, Tumor
PubMed: 38907210
DOI: 10.1186/s12885-024-12495-0 -
Nature Communications Jun 2024Ewing sarcoma is a pediatric bone and soft tissue tumor treated with chemotherapy, radiation, and surgery. Despite intensive multimodality therapy, ~50% patients...
Ewing sarcoma is a pediatric bone and soft tissue tumor treated with chemotherapy, radiation, and surgery. Despite intensive multimodality therapy, ~50% patients eventually relapse and die of the disease due to chemoresistance. Here, using phospho-profiling, we find Ewing sarcoma cells treated with chemotherapeutic agents activate TAM (TYRO3, AXL, MERTK) kinases to augment Akt and ERK signaling facilitating chemoresistance. Mechanistically, chemotherapy-induced JAK1-SQ phosphorylation releases JAK1 pseudokinase domain inhibition allowing for JAK1 activation. This alternative JAK1 activation mechanism leads to STAT6 nuclear translocation triggering transcription and secretion of the TAM kinase ligand GAS6 with autocrine/paracrine consequences. Importantly, pharmacological inhibition of either JAK1 by filgotinib or TAM kinases by UNC2025 sensitizes Ewing sarcoma to chemotherapy in vitro and in vivo. Excitingly, the TAM kinase inhibitor MRX-2843 currently in human clinical trials to treat AML and advanced solid tumors, enhances chemotherapy efficacy to further suppress Ewing sarcoma tumor growth in vivo. Our findings reveal an Ewing sarcoma chemoresistance mechanism with an immediate translational value.
Topics: Sarcoma, Ewing; Humans; Janus Kinase 1; Cell Line, Tumor; Animals; Signal Transduction; Receptor Protein-Tyrosine Kinases; Mice; Intercellular Signaling Peptides and Proteins; Axl Receptor Tyrosine Kinase; Proto-Oncogene Proteins; Bone Neoplasms; Xenograft Model Antitumor Assays; c-Mer Tyrosine Kinase; Antineoplastic Agents; Drug Resistance, Neoplasm; Phosphorylation; Female; STAT6 Transcription Factor
PubMed: 38906855
DOI: 10.1038/s41467-024-49667-2 -
International Journal of Biological... 2024Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune... (Review)
Review
Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune cells and designing synthetic molecules from scratch. Because of the cytotoxic nature, abundance in peripheral blood, and maturation of genetic engineering techniques, T cells have become the most commonly engineered immune cells to date. Represented by chimeric antigen receptor (CAR)-T therapy, T cell-based immunotherapy has revolutionized the clinical treatment of hematological malignancies. However, serious side effects and limited efficacy in solid tumors have hindered the clinical application of cellular immunotherapy. To address these limitations, various innovative strategies regarding synthetic cells and molecules have been developed. On one hand, some cytotoxic immune cells other than T cells have been engineered to explore the potential of targeted elimination of tumor cells, while some adjuvant cells have also been engineered to enhance the therapeutic effect. On the other hand, diverse synthetic cellular components and molecules are added to engineered immune cells to regulate their functions, promoting cytotoxic activity and restricting side effects. Moreover, novel bioactive materials such as hydrogels facilitating the delivery of therapeutic immune cells have also been applied to improve the efficacy of cellular immunotherapy. This review summarizes the innovative strategies of synthetic cells and molecules currently available in cellular immunotherapies, discusses the limitations, and provides insights into the next generation of cellular immunotherapies.
Topics: Humans; Immunotherapy; Neoplasms; Animals; Artificial Cells; Receptors, Chimeric Antigen; T-Lymphocytes; Immunotherapy, Adoptive
PubMed: 38904025
DOI: 10.7150/ijbs.94346