-
BMJ Case Reports Jun 2024A patient in his 20s presented with a change in the appearance of his left eye with evidence of relative afferent pupillary defect. Imaging revealed a giant...
A patient in his 20s presented with a change in the appearance of his left eye with evidence of relative afferent pupillary defect. Imaging revealed a giant frontoethmoidal osteoma, a benign sinonasal tumour, invading three-quarters of the orbit. Multidisciplinary discussion involving opthalmology, maxillofacial surgery, neurosurgery and otolaryngology resulted in the decision to attempt entirely endoscopic excision of this lesion, which was performed with successful outcomes. This case demonstrates how a sinonasal osteoma should be considered in the differential diagnosis for a patient presenting with proptosis or other eye signs suggestive of compression of the orbital compartment. This case report and literature review highlights the possibility of managing giant sinonasal osteomas with orbital extension through a completely endoscopic approach.
Topics: Humans; Osteoma; Male; Endoscopy; Paranasal Sinus Neoplasms; Ethmoid Bone; Orbital Neoplasms; Ethmoid Sinus; Orbit; Frontal Sinus; Tomography, X-Ray Computed; Young Adult; Exophthalmos; Diagnosis, Differential; Adult
PubMed: 38926120
DOI: 10.1136/bcr-2023-259236 -
Anticancer Research Jul 2024Methotrexate (MTX) resistance in osteosarcoma leads to a very poor prognosis. In the present study, in order to further understand the basis and ramifications of MTX...
Reduced Malignancy of Super Methotrexate-resistant Osteosarcoma Cells With Dihydrofolate Reductase Amplification Despite Paradoxical Gain of Oncogenic PI3K/AKT/mTOR and c-MYC expression.
BACKGROUND/AIM
Methotrexate (MTX) resistance in osteosarcoma leads to a very poor prognosis. In the present study, in order to further understand the basis and ramifications of MTX resistance in osteosarcoma, we selected an osteosarcoma cell line that has a 5,500-fold-increased MTX IC Materials and Methods: The super MTX-resistant 143B osteosarcoma cells (143B-MTX) were selected from MTX-sensitive parental human 143B osteosarcoma cells (143B-P) by continuous culture with step-wise increased amounts of MTX. To compare the malignancy of 143B-MTX and 143B-P, colony-formation capacity was compared with clonogenic assays on plastic and in soft agar. In addition, tumor growth was compared with orthotopic xenograft mouse models of osteosarcoma. Expression of dihydrofolate reductase (DHFR), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and myelocytomatosis oncogene (MYC) was examined with western immunoblotting and compared in 143B-MTX and 143B-P cells.
RESULTS
143B-MTX had a 5,500-fold increase in the MTX IC compared to the parental 143B-P cells. Expression of DHFR was increased 10-fold in 143B-MTX compared to 143B-P (p<0.01). 143B-MTX cells had reduced colony-formation capacity on plastic (p=0.032) and in soft agar (p<0.01) compared to 143B-P and reduced tumor growth in orthotopic xenograft mouse models (p<0.001). These results demonstrate that 143B-MTX had reduced malignancy. 143B-MTX also showed an increased expression of PI3K (p<0.01), phosphorylated (activated) AKT (p=0.031), phosphorylated mTOR (p=0.043), and c-MYC (p=0.024) compared to 143B-P.
CONCLUSION
The present study demonstrates that the increased expression of DHFR, PI3K/AKT/mTOR and c-MYC appears to be linked to super MTX resistance and, paradoxically, to reduced malignancy. The present results suggest that DHFR may be a powerful tumor suppressor when highly amplified.
Topics: Osteosarcoma; Methotrexate; Humans; Tetrahydrofolate Dehydrogenase; Animals; Drug Resistance, Neoplasm; TOR Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Cell Line, Tumor; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-myc; Mice; Xenograft Model Antitumor Assays; Bone Neoplasms; Gene Amplification; Signal Transduction; Mice, Nude; Antimetabolites, Antineoplastic
PubMed: 38925854
DOI: 10.21873/anticanres.17090 -
Anticancer Research Jul 2024A "Think Tank for Osteosarcoma" medical advisory board meeting was held in Santa Monica, CA, USA on February 2-3, 2024. The goal was to develop a strategic approach to... (Review)
Review
A "Think Tank for Osteosarcoma" medical advisory board meeting was held in Santa Monica, CA, USA on February 2-3, 2024. The goal was to develop a strategic approach to prevent recurrence of osteosarcoma. Osteosarcoma metabolism and the genomic instability of osteosarcoma, immunotherapy for osteosarcoma, CAR-T cell therapy, DeltaRex-G tumor-targeted gene therapy, repurposed drugs, alternative medicines, and personalized medicine were discussed. Only DeltaRex-G was voted on. The conclusions were the following: No intervention has been demonstrated to improve survival in a clinical trial. Additionally, the consensus (10/12 in favor) was that DeltaRex-G without immunotherapy may be administered for up to one year. Phase 2/3 randomized studies of DeltaRex-G should be performed to determine whether the incidence of recurrence could be reduced in high-risk individuals. Furthermore, a personalized approach using drugs with minimal toxicity could be attempted with the acknowledgement that there are no efficacy data to base this on. Repurposed drugs and alternative therapies should be tested in mouse models of osteosarcoma. Moreover, unmodified IL-2 primed Gamma Delta (NK) cell therapy may be used to prevent recurrence. Lastly, rapid development of CAR-T cell therapy is recommended, and an institute dedicated to the study of osteosarcoma is needed.
Topics: Osteosarcoma; Humans; Bone Neoplasms; Animals; Immunotherapy; Precision Medicine; Advisory Committees; Neoplasm Recurrence, Local
PubMed: 38925853
DOI: 10.21873/anticanres.17139 -
Anticancer Research Jul 2024Complete surgical resection with negative margins remains the cornerstone for curative treatment of rectal cancer; however, local recurrence can pose a significant...
BACKGROUND/AIM
Complete surgical resection with negative margins remains the cornerstone for curative treatment of rectal cancer; however, local recurrence can pose a significant challenge. Herein, we aimed to introduce a novel surgical technique for combined resection of the pubic arch and ischial bone in the context of treating recurrent rectal cancer.
CASE REPORT
We present a case of a patient with a fourth local recurrence of rectal cancer, with no evidence of distant metastasis. The tumor directly invaded the posterior wall of the pubic arch. To achieve complete tumor resection, an osteotomy was performed using a thread wire saw at the bilateral pubic rami and ischial bones. Intraoperative frozen section analysis (rapid tissue examination) was conducted on tissue samples from the lateral margins of the planned osteotomy line. Samples were negative for adenocarcinoma (cancerous cells). The combined resection of the pubic arch and ischial bone was successfully performed with negative margins for adenocarcinoma, as confirmed by frozen section analysis.
CONCLUSION
Mastery of the surgical technique for combined resection of the pubic arch and ischial bone may be clinically significant for achieving complete resection in cases of multiple resections for locally recurrent rectal cancer.
Topics: Humans; Rectal Neoplasms; Neoplasm Recurrence, Local; Pubic Bone; Ischium; Male; Osteotomy; Middle Aged; Aged; Adenocarcinoma; Female
PubMed: 38925850
DOI: 10.21873/anticanres.17136 -
Blood Advances Jun 2024Somatic mutations in the TET2 gene occur more frequently with age, imparting an intrinsic hematopoietic stem cell (HSC) advantage and contributing to a phenomenon termed...
Somatic mutations in the TET2 gene occur more frequently with age, imparting an intrinsic hematopoietic stem cell (HSC) advantage and contributing to a phenomenon termed clonal hematopoiesis of indeterminate potential (CHIP). Individuals with TET2-mutant CHIP have a higher risk of developing myeloid neoplasms and other aging-related conditions. Despite its role in unhealthy aging, the extrinsic mechanisms driving TET2-mutant CHIP clonal expansion remain unclear. We previously showed an environment containing TNF favours TET2-mutant HSC expansion in vitro. We therefore postulated that age-related increases in TNF also provide an advantage to HSCs with TET2-mutations in vivo. To test this hypothesis, we generated mixed bone marrow chimeric mice of old wild-type (WT) and TNF-/- genotypes reconstituted with WT CD45.1+ and Tet2-/-CD45.2+ HSCs. We show that age-associated increases in TNF dramatically increased the expansion of Tet2-/-cells in old WT recipient mice, with strong skewing towards the myeloid lineage. This aberrant myelomonocytic advantage was mitigated in old TNF-/- recipient mice, suggesting that TNF signalling is essential for the expansion Tet2-mutant myeloid clones. Examination of human rheumatoid arthritis patients with clonal hematopoiesis revealed that hematopoietic cells carrying certain mutations, including in TET2, may be sensitive to reduced TNF bioactivity following blockade with adalimumab. This suggests that targeting TNF may reduce the burden of some forms of CHIP. To our knowledge, this is the first evidence to demonstrate that TNF has a causal role in driving TET2-mutant CHIP in vivo. These findings highlight TNF as a candidate therapeutic target to control TET2-mutant CHIP.
PubMed: 38924753
DOI: 10.1182/bloodadvances.2023011833 -
Cell Biochemistry and Function Jun 2024Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration... (Review)
Review
Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron-dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano-drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions.
Topics: Ferroptosis; Osteosarcoma; Humans; Bone Neoplasms; Antineoplastic Agents; Immunotherapy; Animals
PubMed: 38924104
DOI: 10.1002/cbf.4080 -
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 -
Annals of the Academy of Medicine,... Jan 2024The most prevalent type of fragility fractures is osteoporotic vertebral fractures (OVFs). However, only a few studies have examined the relationship between...
INTRODUCTION
The most prevalent type of fragility fractures is osteoporotic vertebral fractures (OVFs). However, only a few studies have examined the relationship between anti-osteoporosis treatments and malignancy-related mortality following an OVF. The goal of this study is to determine the effect of anti-osteoporosis therapy on mortality in OVF patients with and without cancer.
METHOD
Data from older people over the age of 65 who were hospitalised for OVFs between 1 January 2003 and 31 December 2018 were analysed retrospectively. A total of 6139 persons getting osteoporosis treatment and 28,950 who did not receive treatment were analysed, together with 2 sets of patients, comprising cancer patients (794) and cancer-free patients (5342), using anti-osteoporosis medication or not, in 1:1 propensity score-matched analyses. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.
RESULTS
In all, 35,089 patients with OVFs were included in the population; 29,931 people (85.3%) were women, and the mean (standard deviation) age was 78.13 (9.27) years. Overall survival was considerably higher in those undergoing osteoporosis therapy. This was true both for those without cancer (adjusted HR 0.55; 95% CI 0.51-0.59; P<.0001) as well as those with cancer (adjusted HR 0.72; 95% CI 0.62-0.84; P<.0001). Even among cancer patients, those who received anti-osteoporotic drugs had a lower mortality rate than those who did not.
CONCLUSION
Our findings suggest that anti-osteoporosis therapy should be initiated regardless of the presence of cancer in the elderly, as it increases survival following OVFs.
Topics: Humans; Aged; Female; Male; Spinal Fractures; Neoplasms; Aged, 80 and over; Osteoporotic Fractures; Retrospective Studies; Bone Density Conservation Agents; Osteoporosis; Singapore; Proportional Hazards Models; Propensity Score; Cohort Studies
PubMed: 38920210
DOI: 10.47102/annals-acadmedsg.202396 -
Annals of the Academy of Medicine,... Jan 2024
Topics: Humans; Osteoporosis; Bone Density Conservation Agents; Neoplasms; Female
PubMed: 38920208
DOI: 10.47102/annals-acadmedsg.20244 -
Expert Review of Hematology Jul 2024Chimeric Antigen Receptor (CAR) T-cells and Bispecific Antibodies (BsAb) are the leading platforms for redirecting the immune system against cells expressing the... (Review)
Review
INTRODUCTION
Chimeric Antigen Receptor (CAR) T-cells and Bispecific Antibodies (BsAb) are the leading platforms for redirecting the immune system against cells expressing the specific antigen, revolutionizing the treatment of hematological malignancies, including multiple myeloma (MM). In MM, drug-resistant relapses are the main therapy-limiting factor and the leading cause of why the disease is still considered incurable. T-cell-engaging therapies hold promise in improving the treatment of MM. However, the effectiveness of these treatments may be hindered by T-cell fitness. T-cell exhaustion is a condition of a gradual decline in effector function, reduced cytokine secretion, and increased expression of inhibitory receptors due to chronic antigen stimulation.
AREAS COVERED
This review examines findings about T-cell exhaustion in MM in the context of T-cell redirecting BsAbs and CAR-T treatment.
EXPERT OPINION
The fitness of T-cells has become an important factor in the development of T-cell redirecting therapies. The way T-cell exhaustion relates to these therapies could affect the further development of CAR and BsAbs technologies, as well as the strategies used for clinical use. Therefore, this review aims to explore the current understanding of T-cell exhaustion in MM and its relationship to these therapies.
Topics: Multiple Myeloma; Humans; T-Lymphocytes; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Antibodies, Bispecific; T-Cell Exhaustion
PubMed: 38919090
DOI: 10.1080/17474086.2024.2370552