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International Journal of Molecular... Jun 2024Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary... (Review)
Review
Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary sequences of mRNAs or other ncRNAs or by directly engaging in protein interactions. Over the past few decades, the pervasiveness of ncRNAs in cell physiology and their pivotal roles in various diseases have been identified. One target regulated by ncRNAs is connexin (Cx), a protein that forms gap junctions and hemichannels and facilitates intercellular molecule exchange. The aberrant expression and misdistribution of connexins have been implicated in central nervous system diseases, cardiovascular diseases, bone diseases, and cancer. Current databases and technologies have enabled researchers to identify the direct or indirect relationships between ncRNAs and connexins, thereby elucidating their correlation with diseases. In this review, we selected the literature published in the past five years concerning disorders regulated by ncRNAs via corresponding connexins. Among it, microRNAs that regulate the expression of Cx43 play a crucial role in disease development and are predominantly reviewed. The distinctive perspective of the ncRNA-Cx axis interprets pathology in an epigenetic manner and is expected to motivate research for the development of biomarkers and therapeutics.
Topics: Humans; RNA, Untranslated; Animals; Connexins; MicroRNAs; Connexin 43; Neoplasms; Gene Expression Regulation; Cardiovascular Diseases; Gap Junctions; Central Nervous System Diseases
PubMed: 38892334
DOI: 10.3390/ijms25116146 -
International Journal of Molecular... Jun 2024Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the...
Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the progression of RCC in vitro and in vivo. Lead challenge of Renca cells with 0.5 μM lead acetate for 10 consecutive passages decreased E-cadherin expression and cell aggregation. Proliferation, colony formation, and wound healing were increased. When lead-challenged cells were injected into mice, tumor size at day 21 was increased; interestingly, this increase was seen in male but not female mice. When mice were challenged with 32 ppm lead in drinking water for 20 weeks prior to tumor cell injection, there was an increase in tumor size in male, but not female, mice at day 21. To investigate the mechanism underlying the sex differences, the expression of sex hormone receptors in Renca cells was examined. Control Renca cells expressed estrogen receptor (ER) alpha but not ER beta or androgen receptor (AR), as assessed by qPCR, and the expression of ERα was increased in tumors in both sexes. In tumor samples harvested from lead-challenged cells, both ERα and AR were detected by qPCR, yet there was a significant decrease in AR seen in lead-challenged tumor cells from male mice only. This was paralleled by a plate-based array demonstrating the same sex difference in BMP-7 gene expression, which was also significantly decreased in tumors harvested from male but not female mice; this finding was validated by immunohistochemistry. A similar expression pattern was seen in tumors harvested from the mice challenged with lead in the drinking water. These data suggest that lead promotes RCC progression in a sex-dependent via a mechanism that may involve sex-divergent changes in BMP-7 expression.
Topics: Animals; Female; Carcinoma, Renal Cell; Male; Bone Morphogenetic Protein 7; Mice; Kidney Neoplasms; Cell Line, Tumor; Cell Proliferation; Lead; Receptors, Androgen; Gene Expression Regulation, Neoplastic; Humans; Estrogen Receptor alpha; Sex Factors
PubMed: 38892327
DOI: 10.3390/ijms25116139 -
International Journal of Molecular... May 2024Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA)...
Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [At]PSMA-5 was administered to both normal male ICR mice ( = 85) and cynomolgus monkeys ( = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( = 10 per group) and 14 days ( = 5 per group). Monkeys were observed 24 h post-administration of [At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of At using a cyclotron supports its applicability for clinical use.
Topics: Animals; Male; Prostatic Neoplasms; Mice; Tissue Distribution; Mice, Inbred ICR; Astatine; Alpha Particles; Humans; Macaca fascicularis; Glutamate Carboxypeptidase II; Radiopharmaceuticals
PubMed: 38891856
DOI: 10.3390/ijms25115667 -
Cells Jun 2024Chondrosarcoma (ChS), a malignant cartilage-producing tumor, is the second most frequently diagnosed osseous sarcoma after osteosarcoma. It represents a very... (Review)
Review
Chondrosarcoma (ChS), a malignant cartilage-producing tumor, is the second most frequently diagnosed osseous sarcoma after osteosarcoma. It represents a very heterogeneous group of malignant chemo- and radiation-resistant neoplasms, accounting for approximately 20% of all bone sarcomas. The majority of ChS patients have a good prognosis after a complete surgical resection, as these tumors grow slowly and rarely metastasize. Conversely, patients with inoperable disease, due to the tumor location, size, or metastases, represent a great clinical challenge. Despite several genetic and epigenetic alterations that have been described in distinct ChS subtypes, very few therapeutic options are currently available for ChS patients. Therefore, new prognostic factors for tumor progression as well as new treatment options have to be explored, especially for patients with unresectable or metastatic disease. Recent studies have shown that a correlation between immune infiltrate composition, tumor aggressiveness, and survival does exist in ChS patients. In addition, the intra-tumor microvessel density has been proven to be associated with aggressive clinical behavior and a high metastatic potential in ChS. This review will provide an insight into the ChS microenvironment, since immunotherapy and antiangiogenic agents are emerging as interesting therapeutic options for ChS patients.
Topics: Humans; Chondrosarcoma; Tumor Microenvironment; Bone Neoplasms; Immunotherapy; Angiogenesis Inhibitors
PubMed: 38891109
DOI: 10.3390/cells13110977 -
Trials Jun 2024Hematopoietic cell transplantation (HCT) is a highly invasive and life-threatening treatment for hematological neoplasms and some types of cancer that can challenge the...
The effect of an online acceptance and commitment intervention on the meaning-making process in cancer patients following hematopoietic cell transplantation: study protocol for a randomized controlled trial enhanced with single-case experimental design.
BACKGROUND
Hematopoietic cell transplantation (HCT) is a highly invasive and life-threatening treatment for hematological neoplasms and some types of cancer that can challenge the patient's meaning structures. Restoring meaning (i.e., building more flexible and significant explanations of the disease and treatment burden) can be aided by strengthening psychological flexibility by means of an Acceptance and Commitment Therapy (ACT) intervention. Thus, this trial aims to examine the effect of the ACT intervention on the meaning-making process and the underlying mechanisms of change in patients following HCT compared to a minimally enhanced usual care (mEUC) control group. The trial will be enhanced with a single-case experimental design (SCED), where ACT interventions will be compared between individuals with various pre-intervention intervals.
METHODS
In total, 192 patients who qualify for the first autologous or allogeneic HCT will be recruited for a two-armed parallel randomized controlled trial comparing an online self-help 14-day ACT training to education sessions (recommendations following HCT). In both conditions, participants will receive once a day a short survey and intervention proposal (about 5-10 min a day) in the outpatient period. Double-blinded assessment will be conducted at baseline, during the intervention, immediately, 1 month, and 3 months after the intervention. In addition, 6-9 participants will be invited to SCED and randomly assigned to pre-intervention measurement length (1-3 weeks) before completing ACT intervention, followed by 7-day observations at the 2nd and 3rd post-intervention measure. The primary outcome is meaning-related distress. Secondary outcomes include psychological flexibility, meaning-making coping, meanings made, and well-being as well as global and situational meaning.
DISCUSSION
This trial represents the first study that integrates the ACT and meaning-making frameworks to reduce meaning-related distress, stimulate the meaning-making process, and enhance the well-being of HCT recipients. Testing of an intervention to address existential concerns unique to patients undergoing HCT will be reinforced by a statistically rigorous idiographic approach to see what works for whom and when. Since access to interventions in the HCT population is limited, the web-based ACT self-help program could potentially fill this gap.
TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT06266182. Registered on February 20, 2024.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Acceptance and Commitment Therapy; Randomized Controlled Trials as Topic; Treatment Outcome; Internet-Based Intervention; Single-Case Studies as Topic; Adaptation, Psychological; Time Factors; Patient Education as Topic; Health Knowledge, Attitudes, Practice; Quality of Life; Hematologic Neoplasms
PubMed: 38890709
DOI: 10.1186/s13063-024-08235-1 -
BMC Oral Health Jun 2024Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of... (Review)
Review
BACKGROUND
Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity.
CASE PRESENTATION
This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and β-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital.
CONCLUSIONS
OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.
Topics: Female; Humans; Young Adult; beta Catenin; Diagnosis, Differential; Keratin-19; Mandibular Neoplasms; Odontogenic Tumors; Transcription Factors; Tumor Suppressor Proteins
PubMed: 38890602
DOI: 10.1186/s12903-024-04471-8 -
BMJ Open Jun 2024Many patients referred for suspicion of myelodysplastic neoplasm (MDS) are subjected to unnecessary discomfort from bone marrow aspiration, due to the low disease...
Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in myelodysplastic neoplasms (MPO-MDS-Valid): protocol for a multicentre diagnostic accuracy study.
INTRODUCTION
Many patients referred for suspicion of myelodysplastic neoplasm (MDS) are subjected to unnecessary discomfort from bone marrow aspiration, due to the low disease prevalence in this population. Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression could rule out MDS with sensitivity and negative predictive value estimates close to 100%, ultimately obviating the need for bone marrow aspiration in up to 35% of patients. However, the generalisability of these findings is uncertain due to the limited sample size, the enrolment of patients at a single study site, and the reliability issues associated with laboratory-developed tests and varying levels of operator experience. This study aims to validate the accuracy attributes of peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis in an independent multicentre sample.
METHODS AND ANALYSIS
The MPO-MDS-Valid project is a cross-sectional diagnostic accuracy study comparing an index test to a reference standard. Consecutive adult patients referred for suspicion of MDS are being recruited at seven university hospitals and one cancer centre in France. At each site, flow cytometric analysis of peripheral blood samples is performed by operators who are blinded to the reference diagnosis. A central adjudication committee whose members are unaware of the index test results will determine the reference diagnosis of MDS, based on cytomorphological evaluation of bone marrow performed in duplicate by experienced hematopathologists. The target sample size is 400 patients and the anticipated study recruitment completion date is 31 December 2025.
ETHICS AND DISSEMINATION
An institutional review board (Comité de Protection des Personnes Nord-Ouest III, Caen, France) approved the protocol, prior to the start of the study. Participants are recruited using an opt-out approach. Efforts will be made to publish the primary results within 6 months after study completion.
TRIAL REGISTRATION NUMBER
NCT05175469.
Topics: Humans; Flow Cytometry; Peroxidase; Neutrophils; Myelodysplastic Syndromes; Cross-Sectional Studies; Reproducibility of Results; France; Male; Multicenter Studies as Topic; Female; Sensitivity and Specificity; Adult
PubMed: 38889946
DOI: 10.1136/bmjopen-2023-081200 -
Environmental Health Perspectives Jun 2024Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and cause-specific cancers warrants...
BACKGROUND
Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and cause-specific cancers warrants investigation.
OBJECTIVE
The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers.
METHODS
In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors.
RESULTS
Over a median follow-up of 13.6 y (range: 12.7-14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed ( for nonlinearity ). In comparison with individuals exposed to soft water (), the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause cancer were 1.00 (95% CI: 0.98, 1.02) for those exposed to moderate hard water (), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water () and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water (). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer.
DISCUSSION
Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. https://doi.org/10.1289/EHP13606.
Topics: Humans; Neoplasms; Prospective Studies; Male; Female; Middle Aged; United Kingdom; Aged; Water Supply; Adult; Biological Specimen Banks; Proportional Hazards Models; Environmental Exposure; UK Biobank
PubMed: 38889166
DOI: 10.1289/EHP13606 -
Journal of Medical Case Reports Jun 2024The aim of this case report is to evaluate minimally invasive stabilization using screws and cement for acetabular metastatic tumor and summarize the indications and...
BACKGROUND
The aim of this case report is to evaluate minimally invasive stabilization using screws and cement for acetabular metastatic tumor and summarize the indications and contraindications for minimally invasive stabilization of acetabular metastatic tumors with screw and cement techniques.
CASE PRESENTATION
Under imaging guidance, a patient with acetabular metastatic tumor was treated with hollow screw combined with bone cement fixation. Ischial screw, ascending branch screw, and anterior and posterior screws were inserted to firmly fix the anterior and posterior column of the acetabulum. At the same time, the third screw connected the anterior and posterior columns together, combined with bone cement into the fracture site to further increase local stability and resist bone defects caused by local tumor osteolysis. The patient was a 52-year-old Uygur male. Herein, we summarize his clinical symptoms and operation. Differences in visual analog scale and walking function (Musculoskeletal Tumor Society) before operation and at 2 months, 6 months, and 12 months after operation were compared.
RESULTS
Postoperative complications and tumor progression were recorded. The patient was followed up for 16 months, and the operative time was 60 minutes. In total, 20 ml of bone cement was injected into the acetabular posterior column and the top of the acetabulum. VIsual analog scale score was 8 before operation, 3 at 2 months, 3 at 6 months, and 2 at 12 months after operation. Musculoskeletal Tumor Society function was 13 before operation, 23 at 2 months, 25 at 6 months, and 26 at 12 months after operation. During follow-up, no cement leakage, fever, hip nerve injury, pulmonary embolism, or imaging findings of further destruction of the acetabulum and surrounding bone were noted.
CONCLUSION
This case report shows that the treatment of acetabular metastatic cancer with minimally invasive stabilization using screws and cement under the C arm can effectively relieve pain and enhance the strength of the pelvis, and is innovative and feasible.
Topics: Humans; Male; Acetabulum; Middle Aged; Bone Cements; Bone Neoplasms; Bone Screws; Minimally Invasive Surgical Procedures; Treatment Outcome
PubMed: 38886832
DOI: 10.1186/s13256-024-04604-1 -
Cell Death & Disease Jun 2024Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new...
Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new therapeutic schemes, but most of which are not satisfactory. Single-cell RNA sequencing was performed in PDX mouse models with or without TCC therapy. 2-'O-Methylation modification and multiplex immunofluorescence staining were used to explore the function and mechanism of SAMD4B in the immune context of HCC. Here, we propose for the first time a synergistic immunochemotherapy that exerts a potent antitumour effect for patients with advanced hepatocellular carcinoma (HCC) in clinical practice based on three common antitumour drugs and found that HCC patients with new synergistic immunochemotherapy had better three-year overall survival (p = 0.004) and significantly higher survival ratio (increased by 2.3 times) than the control group. We further reveal the immunoregulatory mechanism of synergistic immunochemotherapy through 2'-O-Methylation modification mediated by SAMD4B, a tumour suppressor gene. Mechanistically, SAMD4B, increased by the reduced mutations of upstream genes NOTCH1 and NOTCH2, affected the instability of APOA2 mRNA by 2-'O-Methylation modification of the C-terminus. The decreased APOA2 further attenuated programmed death ligand 1 (PD-L1) level with a direct interaction pattern. The high-SAMD4B tumour tissues contained fewer native CD29+CD8+ T cells, which improved immune microenvironment to achieve the effect of antitumour effect. Overall, we developed a potent synergistic immunochemotherapy strategy that exerts an efficient anti-HCC effect inducing SAMD4B-APOA2-PD-L1 axis to inhibit tumour immune evasion.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Animals; Humans; Mice; Immunotherapy; B7-H1 Antigen; Cell Line, Tumor; Male; Tumor Microenvironment; Female
PubMed: 38886351
DOI: 10.1038/s41419-024-06699-2