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Frontiers in Pharmacology 2024The members retinoic acid receptors (RARs) (α, β, and γ) and retinoid X receptors (RXRs) (α, β, and γ) belong to the retinoid receptor family. They regulate the...
INTRODUCTION
The members retinoic acid receptors (RARs) (α, β, and γ) and retinoid X receptors (RXRs) (α, β, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates.
OBJECTIVE
This study's main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients.
METHODOLOGY
investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells.
RESULTS
Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through and study.
DISCUSSION
Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.
PubMed: 38910889
DOI: 10.3389/fphar.2024.1361679 -
Clinical Case Reports Jun 2024Talar metastases from malignant tumors are rare and poorly documented. Treatment requires gradual relief of pain and preservation of function, with a choice between...
Talar metastases from malignant tumors are rare and poorly documented. Treatment requires gradual relief of pain and preservation of function, with a choice between palliative measures and surgery. This case indicates that total talar replacement is an effective intervention for localized talar metastases and highlights the importance of early intervention. A 48-year-old man was diagnosed with a pathologic talar fracture due to talar metastases was observed after 8 years of chemotherapy following a diagnosis of lung adenocarcinoma. Despite radiotherapy, the patient's activities of daily living (ADLs) deteriorated due to pain on walking, prompting a request for surgical intervention. Total talar replacement was performed, allowing the patient to begin full weight-bearing ambulation 2 weeks post-operatively. Total talar replacement appears to be an effective treatment for localized talar metastases and should be performed as early as possible.
PubMed: 38910834
DOI: 10.1002/ccr3.9049 -
Cureus May 2024Breast metastases of extramammary origin are an extremely rare entity. Solid organ metastases to the breast include malignant melanoma, epithelial carcinoma...
Breast metastases of extramammary origin are an extremely rare entity. Solid organ metastases to the breast include malignant melanoma, epithelial carcinoma (adenocarcinoma and squamous cell carcinoma of the lung and gastrointestinal tract), and sarcoma. A breast neoplasm can be caused by a primary tumor, in-transit metastasis, breast metastasis, and skin metastasis. A 42-year-old female patient presented with a hyperpigmented lesion on the first finger of her left hand. An incisional biopsy was carried out, reporting pigmented epithelioid melanoma. Amputation of the finger was performed, as well as an axillary sentinel lymph node excision. Later during the treatment and follow-up by medical oncology, a breast tumor was located, followed by a protocol and the approach of possible differential diagnoses. Finally, it was characterized as metastatic cutaneous melanoma. The therapeutic approach regarding the possible origin of the metastatic neoplastic character of breast tumors culminated in this case in the palliative treatment with immunotherapy of cutaneous malignant melanoma. The diagnosis of breast metastases from cutaneous malignant melanoma is a real challenge, so an extensive history and high clinical suspicion are crucial in order to provide adequate treatment, despite the gloomy prognosis.
PubMed: 38910784
DOI: 10.7759/cureus.60931 -
Cureus May 2024Background Gastric adenocarcinoma (GCA) poses a significant global health burden due to its prevalence and high morbidity and mortality rates. GCA is classified into...
Background Gastric adenocarcinoma (GCA) poses a significant global health burden due to its prevalence and high morbidity and mortality rates. GCA is classified into three main histological types: well-differentiated (intestinal type), poorly differentiated (diffuse type), and mixed or indeterminate forms. These types vary in causes, epidemiology, and genetics, with the diffuse type often associated with the worst prognosis. Endoscopic biopsy is the primary method for characterization, but it has its limitations. There is potential in using contrast-enhanced computed tomography (CT) to differentiate between histological subtypes of gastric adenocarcinoma, which could aid subtype differentiation. Building on this, our study aims to assess CT's effectiveness in distinguishing between broad histological groups of gastric adenocarcinoma based on enhancement patterns, contributing to improved diagnostic accuracy Objective Our research focuses on evaluating the effectiveness of multiphasic contrast-enhanced computed tomography (CECT) in distinguishing between the three broad histopathological subtypes of gastrointestinal cancers. Methods This study was a prospective, analytical observational study that was approved and carried out in our institutional tertiary care hospital. Consecutive individuals who had undergone endoscopic-guided biopsy and demonstrated histological evidence of GCA were taken into consideration for participation in the study. In order to complete the clinical staging process, further multiphasic CT scans were carried out on each of the fifty patients and were categorised accordingly based on the findings of histopathology. Results In the differentiated type, segmental distribution was: 5.5% upper segment, 16.7% middle segment, 66.7% lower segment, and 11.1% diffuse type. Esophageal involvement was 5.6%, duodenal involvement was similar, and lymph node involvement was approximately 38.8%. TNM staging: 38.8% IIIB, 22.2% III, 27.8% IVA, and 11.1% IVB. In the undifferentiated type, segmental distribution: 6.2% upper segment, 31.2% middle segment, 50.0% lower segment, and 12.5% diffuse type. Esophageal involvement was around 6.25%, duodenal involvement was 18.75%, and lymph node involvement was about 71.8%. TNM staging: 34.4% IIIB, 21.8% III, 28.1% IVA, and 15.6% IVB. Conclusion Multiphasic CT evaluations provide valuable insights into the prognostic aspects of gastric carcinomas by assessing peak enhancement. Differentiated tumors typically exhibit arterial phase enhancement, while undifferentiated tumors show venous phase enhancement, reflecting their microvascular architecture. Recent studies emphasize the importance of understanding gastric carcinoma characteristics for diagnosis and prognosis. Our research aligns with this, revealing distinct contrast enhancement patterns between differentiated and undifferentiated types. However, discrepancies in histological classifications and contrast enhancement patterns across studies warrant further investigation. Integrating histopathological and radiological insights is essential for accurate diagnosis and treatment planning.
PubMed: 38910671
DOI: 10.7759/cureus.60841 -
Journal of Radiology Case Reports 2024Rectal cancer Is a Common malignant pathology; its usual spread in volves the liver and lungs. The occurrence of renal metastases is exceptional. CT scanning aims to...
Rectal cancer Is a Common malignant pathology; its usual spread in volves the liver and lungs. The occurrence of renal metastases is exceptional. CT scanning aims to evaluate extension and may incidentally reveal a renal mass, which can be better characterized through MRI and ultrasound. We describe a case of a solitary renal metastasis from rectal cancer and underscore the significant role of imaging in positively diagnosing this uncommon pathology.
Topics: Humans; Rectal Neoplasms; Kidney Neoplasms; Tomography, X-Ray Computed; Male; Magnetic Resonance Imaging; Middle Aged; Adenocarcinoma; Diagnosis, Differential
PubMed: 38910585
DOI: 10.3941/jrcr.v18i1.5233 -
Ear, Nose, & Throat Journal Jun 2024The primary nasopharyngeal papillary adenocarcinoma (NPPA) is extremely rare which accounts for less than 0.48% of all malignant neoplasms in the nasopharynx. The...
The primary nasopharyngeal papillary adenocarcinoma (NPPA) is extremely rare which accounts for less than 0.48% of all malignant neoplasms in the nasopharynx. The clinical features, diagnosis, and treatment of NPPA have not been well described. We present 2 patients with NPPA that were treated with total endoscopic resection and radiotherapy at Vietnam National Cancer Hospital. Through these cases and reviewing of the literature, we provide deeper understanding of NPPA to highlight clinical pathological characteristics and the optimal treatment strategy for patients with pathologically confirmed NPPA. Our 2 cases were successfully treated and remained disease-free 4 years after treatment. The NPPA was usually an indolent tumor with polypoid appearance and slow growth rate and has a good prognosis. Surgical excision, including endonasal endoscopic excision with or without adjuvant radiotherapy, was most effective with a localized and operable tumor.
PubMed: 38910362
DOI: 10.1177/01455613241264440 -
Yonsei Medical Journal Jul 2024Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and... (Comparative Study)
Comparative Study
PURPOSE
Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib.
MATERIALS AND METHODS
We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias.
RESULTS
Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, =0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, =0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank =0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank =0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all >0.05).
CONCLUSION
Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.
Topics: Humans; Nivolumab; Carcinoma, Hepatocellular; Phenylurea Compounds; Pyridines; Sorafenib; Liver Neoplasms; Male; Female; Retrospective Studies; Middle Aged; Aged; Adult; Progression-Free Survival
PubMed: 38910299
DOI: 10.3349/ymj.2023.0263 -
Asian Journal of Surgery Jun 2024
PubMed: 38910085
DOI: 10.1016/j.asjsur.2024.05.292 -
International Journal of Hyperthermia :... 2024Microwave ablation (MWA) is a widely adopted treatment technique for hepatocellular carcinoma (HCC). However, MWA alone is of limited use and has a high recurrence rate....
BACKGROUND
Microwave ablation (MWA) is a widely adopted treatment technique for hepatocellular carcinoma (HCC). However, MWA alone is of limited use and has a high recurrence rate. Transforming growth factor-β1 (TGF-β1) is recognized as a potential therapeutic target for HCC patients. Therefore, this study was designed to investigate whether the TGF-β1 inhibitor could increase the efficacy of MWA therapy for HCC treatment.
METHODS
In vitro, HCC cells challenged with TGF-β1 inhibitor (SB-525334), or normal saline were then heated by microwave. Methyl tetrazolium assays were performed to detect cell survival rate and half-maximal drug inhibitory concentration (IC50). Cell viability and apoptosis were detected by cell counting kit-8 assays, flow cytometry and western blotting. In vivo, the mice injected with HepG2 cells received oral gavage of SB-525334 (20 mg/kg) or normal saline and MWA at a power of 15 W. Tumor volume was recorded. Expression of Ki67 and apoptosis-related proteins were detected by immunohistochemistry and western blotting. TUNEL assays were used to detect cell death ratio. Histopathological changes were examined by hematoxylin and eosin staining. The mechanisms associated with the function of MWA combined with TGF-β1 inhibitor in HCC development were explored by western blotting.
RESULTS
Combination of MWA and SB-525334 decreased the survival rate and promoted the apoptosis of HCC cells compared with MWA alone. SB-525334 enhanced the suppressive effect of MWA on tumor growth and amplified cell apoptosis. Mechanistically, MWA collaborated with SB-525334 inhibitor inactivated the TGF-β1/Smad2/Smad3 pathway.
CONCLUSION
TGF-β1 inhibitor enhances the therapeutic effect of MWA on HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Transforming Growth Factor beta1; Animals; Humans; Mice; Microwaves; Apoptosis; Mice, Nude; Male; Hep G2 Cells; Mice, Inbred BALB C
PubMed: 38909985
DOI: 10.1080/02656736.2024.2359496 -
Journal of Gynecologic Oncology Jun 2024Biomarkers reflecting real-time response to therapy and recurrence are lacking. We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA)...
OBJECTIVE
Biomarkers reflecting real-time response to therapy and recurrence are lacking. We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA) mutations in endometrial cancer (EC) and ovarian cancer (OC) patients.
METHODS
EC/OC patients undergoing primary surgery were consented for tissue banking and 2-year serial blood draws. Tumor tissue DNA and plasma ctDNA underwent next generation sequencing using a targeted gene panel to identify somatic mutations.
RESULTS
Of 44 patients (24 EC, 17 OC, 2 synchronous endometrial and ovarian carcinomas [SEOC] and 1 endocervical adenocarcinoma [EA]) at least one somatic mutation was identified in tumor tissue in 40 (91%, 20/24 EC, all OC/SEOC/EA), and in preoperative plasma ctDNA in 12 (27%) patients (6/24 [25%] EC and 6/17 [35%] OC). Detection of preoperative ctDNA mutations was associated with advanced stage, higher preoperative CA125, and disease recurrence. In 5/12 (42%) patients with preoperative ctDNA mutations, examination/imaging suggested clinical stage I however final pathology revealed stage II/III. In 11 patients where serial timepoints were assessed during treatment for ctDNA and CA125, ctDNA clearance preceded normalization of CA125. Thirteen patients developed recurrent disease (4 EC, 8 OC, 1 EA); 8 in whom ctDNA mutations were detected postoperatively, and 4 followed through time of recurrence with ctDNA mutations identified 2-5 months prior to clinical/radiologic/biomarker progression in 3.
CONCLUSION
ctDNA can reflect larger tumor volume/metastases, treatment response and recurrence in EC and OC. Careful patient selection is critical to direct resources to patients most likely to benefit, considering disease burden and risk group.
PubMed: 38909641
DOI: 10.3802/jgo.2025.36.e5