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World Journal of Surgery Jun 2024In colorectal cancer, the morphological categorization of fibrotic cancer stroma in the invasive frontal zone of the primary tumor is well reflected in the prognosis....
BACKGROUND/PURPOSE
In colorectal cancer, the morphological categorization of fibrotic cancer stroma in the invasive frontal zone of the primary tumor is well reflected in the prognosis. Conversely, the histological characteristics of pancreatic cancer (PC) reveal fibrotic hyperplasia of stroma known as desmoplasia; however, its characterization is unknown. Therefore, this study aimed to evaluate the prognostic factors according to the histological categorization of desmoplastic reactions in PC.
METHODS
We retrospectively enrolled 167 patients who underwent curative resection for PC. The desmoplastic pattern was histologically classified as mature, intermediate, or immature. Clinicopathological features were evaluated, and disease-free and overall survival (OS) were analyzed in the three groups. Prognostic factors were assessed using univariate and multivariate analyses.
RESULTS
In total, 19 mature, 87 intermediate, and 61 immature desmoplastic patterns were evaluated. Jaundice decompression, white blood cell count, and platelet/lymphocyte ratio were significantly different among the groups. The mature group had a better disease-free survival (DFS) prognosis than the other two groups; however, OS did not differ between the groups. Desmoplastic patterns showed significant differences between the three groups for DFS.
CONCLUSIONS
Desmoplastic patterns are a prognostic factor of DFS for PC, with mature desmoplastic reactions associated with good prognosis. Thus, they may aid in individualized therapeutic approaches in patients with PC.
PubMed: 38943046
DOI: 10.1002/wjs.12269 -
British Journal of Cancer Jun 2024Certain paediatric nervous system malignancies have dismal prognoses. Retinoic acid (RA) is used in neuroblastoma treatment, and preclinical data indicate potential...
BACKGROUND
Certain paediatric nervous system malignancies have dismal prognoses. Retinoic acid (RA) is used in neuroblastoma treatment, and preclinical data indicate potential benefit in selected paediatric brain tumour entities. However, limited single-agent efficacy necessitates combination treatment approaches.
METHODS
We performed drug sensitivity profiling of 76 clinically relevant drugs in combination with RA in 16 models (including patient-derived tumouroids) of the most common paediatric nervous system tumours. Drug responses were assessed by viability assays, high-content imaging, and apoptosis assays and RA relevant pathways by RNAseq from treated models and patient samples obtained through the precision oncology programme INFORM (n = 2288). Immunoprecipitation detected BCL-2 family interactions, and zebrafish embryo xenografts were used for in vivo efficacy testing.
RESULTS
Group 3 medulloblastoma (MB) and neuroblastoma models were highly sensitive to RA treatment. RA induced differentiation and regulated apoptotic genes. RNAseq analysis revealed high expression of BCL2L1 in MB and BCL2 in neuroblastomas. Co-treatments with RA and BCL-2/X inhibitor navitoclax synergistically decreased viability at clinically achievable concentrations. The combination of RA with navitoclax disrupted the binding of BIM to BCL-X in MB and to BCL-2 in neuroblastoma, inducing apoptosis in vitro and in vivo.
CONCLUSIONS
RA treatment primes MB and NB cells for apoptosis, triggered by navitoclax cotreatment.
PubMed: 38942989
DOI: 10.1038/s41416-024-02740-5 -
British Journal of Cancer Jun 2024This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic...
BACKGROUND
This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications.
METHODS
This is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007-2020 in the Stockholm-Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification.
RESULTS
In total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status.
CONCLUSION
HER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.
PubMed: 38942987
DOI: 10.1038/s41416-024-02777-6 -
Annals of Hematology Jun 2024Multiple myeloma (MM) is a form of clonal plasma cell malignancy that associates with clinical manifestations such as anemia, hypercalcemia, bone pain, and renal... (Review)
Review
Multiple myeloma (MM) is a form of clonal plasma cell malignancy that associates with clinical manifestations such as anemia, hypercalcemia, bone pain, and renal impairment. Approximately 20-50% of MM patients at initial diagnosis experience renal injury, a vital complication that significantly influences prognosis and quality of life. This review seeks to clarify the multifaceted mechanisms of renal injury in MM, scrutinizing the pathogenic role of monoclonal proteins, the impact of hypercalcemia, and direct renal infiltration by plasma cells. Furthermore, it evaluates current diagnostic approaches, reviews management strategies, and highlights potential avenues for future research. By incorporating the latest scientific evidence and insights, this article aims to provide a comprehensive understanding of MM-associated renal impairment, offering a valuable resource for researchers and clinicians in handling this complex complication.
PubMed: 38942949
DOI: 10.1007/s00277-024-05860-3 -
Scientific Reports Jun 2024Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into...
Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.
Topics: Humans; Cullin Proteins; Female; Prognosis; Breast Neoplasms; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Gene Expression Profiling; MCF-7 Cells; Triple Negative Breast Neoplasms
PubMed: 38942922
DOI: 10.1038/s41598-024-65692-z -
Eye (London, England) Jun 2024We aimed to investigate the prevalence, risk factors, and prognosis of Graves' orbitopathy (GO) in patients with thyroid cancer without a history of hyperthyroidism.
BACKGROUND/OBJECTIVES
We aimed to investigate the prevalence, risk factors, and prognosis of Graves' orbitopathy (GO) in patients with thyroid cancer without a history of hyperthyroidism.
SUBJECTS/METHODS
This retrospective cohort study analysed a sample from the Korean National Health Insurance Service database, which included 1,137,861 subjects from 2002 through 2019. Patients diagnosed with thyroid cancer, without a history of hyperthyroidism, were identified according to the Korean Standard Classification of Disease codes. The study compared the type of surgery, dose of radioactive iodine (RAI), and daily average thyroid hormone dose between patients who developed GO after being diagnosed with thyroid cancer and those who did not develop GO. We analysed the course of GO and the type of treatment.
RESULTS
A total of 8499 cancer patients without a history of hyperthyroidism were identified, among whom 7836 underwent thyroidectomy. Of those who underwent thyroidectomy, 12 developed GO postoperatively. Among the 663 patients who did not undergo thyroidectomy, none developed GO. The prevalence of GO among thyroid cancer patients was 0.14%. The GO group received a significantly higher total RAI dose than the non-GO group (p = 0.036). There were no significant differences in sex, age, type of surgery, rate of RAI treatment, or average thyroid hormone dose between the two groups. One of the 12 patients who developed GO required intravenous steroids.
CONCLUSIONS
Although GO rarely develops in thyroid cancer patients without coexisting hyperthyroidism, the total RAI dose may increase its risk. Further research would help clarify GO's association with thyroid cancer.
PubMed: 38942911
DOI: 10.1038/s41433-024-03197-9 -
Scientific Reports Jun 2024Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic...
Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.
Topics: Humans; Crohn Disease; Ustekinumab; Male; Female; Adult; Treatment Outcome; Middle Aged; Prospective Studies; Follow-Up Studies; Remission Induction; Hungary
PubMed: 38942890
DOI: 10.1038/s41598-024-65987-1 -
British Dental Journal Jun 2024This case presents clinical techniques and materials that may be applied in the management of internal tunnelling root resorption, a rare condition which has little...
This case presents clinical techniques and materials that may be applied in the management of internal tunnelling root resorption, a rare condition which has little published literature.A 25-year-old woman was referred to a specialist centre by her general dental practitioner following an incidental finding of a radiographic radiolucency, suggestive of root resorption associated with tooth 21. A provisional diagnosis of external cervical resorption was made, and following cone beam computed tomography (CBCT), a definitive diagnosis of internal tunnelling root resorption given. Non-surgical endodontic treatment was completed using continuous wave compaction with a calcium-silicate based sealer. No further intervention has been required.A summary of the histology, aetiology, prevalence, diagnosis, management and prognosis of internal tunnelling root resorption is provided. The benefits of CBCT for diagnosing and managing internal tunnelling resorption defects and using continuous wave compaction with a calcium-silicate based sealer, compared to cold obturation techniques, are discussed.
Topics: Humans; Root Resorption; Female; Adult; Incisor; Cone-Beam Computed Tomography; Root Canal Filling Materials; Silicates; Calcium Compounds; Maxilla; Root Canal Therapy
PubMed: 38942857
DOI: 10.1038/s41415-024-7504-7 -
Scientific Reports Jun 2024Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1...
Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.
Topics: Humans; Male; Prostatic Neoplasms; TOR Serine-Threonine Kinases; Gene Expression Regulation, Neoplastic; Disease Progression; Signal Transduction; Cell Line, Tumor; CDC2 Protein Kinase; DNA Methylation; Promoter Regions, Genetic; Cell Proliferation; Down-Regulation; Prognosis; Cell Movement
PubMed: 38942821
DOI: 10.1038/s41598-024-66020-1 -
Scientific Reports Jun 2024This study aimed to investigate the effect of orbital wall decompression surgery and reduction of proptosis on the choroidal vascularity index (CVI) and subfoveal...
This study aimed to investigate the effect of orbital wall decompression surgery and reduction of proptosis on the choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT) in patients with thyroid eye disease (TED). Fifty-one eyes from 38 patients with controlled TED and proptosis were enrolled in this study. The majority of the patients (50.9%) had a clinical activity score (CAS) of zero, and none had a CAS greater than 2. The patients underwent a complete baseline ophthalmologic examination, and their choroidal profile alterations were monitored using enhanced depth imaging optical coherence tomography (EDI-OCT) before and during the three months after surgery. Changes in SFCT, luminance area (LA), total choroidal area (TCA), and the choroidal vascularity index (CVI) were measured as the ratio of LA to TCA in EDI-OCT images. The participants had an average age of 46.47 years, and 22 were female (57.9%). The SFCT of the patients exhibited a significant reduction over the follow-up period, decreasing from 388 ± 103 to 355 ± 95 µm in the first month (p < 0.001) and further decreasing to 342 ± 109 µm by the third month compared to baseline (p < 0.001). The CVI exhibited a drop from 0.685 ± 0.037 at baseline to 0.682 ± 0.035 and 0.675 ± 0.030 at 1 and 3 months post-surgery, respectively. However, these changes were not statistically significant, indicating comparable decreases in both LA and TCA. There was a significant correlation between improved proptosis and reduction in SFCT (p < 0.001) but not with CVI (p = 0.171). In conclusion, during the three months of follow-up following orbital wall decompression, CVI did not change, while SFCT reduced significantly. Additionally, SFCT was significantly correlated with proptosis reduction, whereas CVI was not.
Topics: Humans; Female; Male; Middle Aged; Decompression, Surgical; Graves Ophthalmopathy; Choroid; Tomography, Optical Coherence; Adult; Orbit; Exophthalmos; Aged; Treatment Outcome
PubMed: 38942805
DOI: 10.1038/s41598-024-65884-7