Medical Molecular Morphology最新文献

Pancreatic cancer, a highly fibrotic and hypovascular tumor, is thought to have unique metabolic characteristics in surviving and proliferating in malnutritional microenvironments. In this study, we compared the differences in the ability of pancreatic cancer cells to adapt to glucose-free conditions with liver cancer cells, which are representative of hypervascular tumors. Three pancreatic cancer cells and two liver cancer cells were used to examine the transcriptional expression levels of molecules involved in intracellular amino acid uptake, epithelial-mesenchymal transition (EMT), and cancer stemness under glucose deprivation. The results showed that the proliferative activity of pancreatic cancer cells under glucose deprivation was significantly lower than that of liver cancer cells, but the expression levels of amino acid transporters were significantly higher. Among them, L-type amino acid transporter 1 (LAT1) upregulation was unique in concert with increased expression of the EMT regulator SNAIL and the cancer stemness marker doublecortin-like kinase 1. LAT1 knockdown canceled the upregulation of SNAIL in glucose-starved pancreatic cancer cells, suggesting a mechanistic link between the two molecules. When LAT1 was stimulated by its substrate leucine, the SNAIL expression was upregulated dose-dependently. Collectively, pancreatic cancer cells reprogrammed metabolism to adapt to energy crises involving leucine-induced SNAIL upregulation.

Ovarian cancer (OvCa) is a leading cause of gynecological cancer-related mortality, primarily due to peritoneal dissemination, which facilitates metastasis in the abdominal cavity. This study explored the potential of vitamin D and its synthetic derivatives in mitigating peritoneal dissemination by modulating the behavior of mesothelial cells (MCs). Vitamin D, through its receptor (VDR), is known to influence cancer progression, and our findings demonstrate that vitamin D derivatives can inhibit mesenchymal transition of MCs induced by TGF-β1, a key driver of peritoneal dissemination. This study used patient-derived primary MCs and in vivo mouse model to assess the effects of vitamin D derivatives on cell morphology, gene expression, and OvCa cell adhesion. Two vitamin D derivatives, VDR agonist, showed significant efficacy in maintaining epithelial-like MC morphology, reducing TGF-β1-induced changes, and inhibiting OvCa cell adhesion to the peritoneum, similar to calcitriol. Conversely, the VDR antagonist derivative induced MC apoptosis, highlighting the essential role of vitamin D in MC survival. These findings suggest that vitamin D derivatives could serve as promising therapeutic agents for OvCa by preserving peritoneal homeostasis and preventing metastasis. Further research is required to explore a broader range of derivatives and their underlying molecular mechanisms.

Progastrin-releasing peptide (ProGRP), a neuropeptide, is a stable tumor marker for small cell lung carcinoma (SCLC) and other neuroendocrine tumors, such as medullary thyroid carcinoma. It has recently been reported as highly expressed in Ewing sarcoma (ES) and as a useful marker for this type of tumor. However, the mechanisms underlying ProGRP production remain unclear. This study aimed to elucidate its subcellular localization in human ES cell lines. Three ES cell lines (A-673, SK-N-MC, and SK-NEP-1) and one SCLC line (DMS 53) were transplanted into athymic mice. After 3-4 weeks, the tumors were excised, and the expression and localization of ProGRP were examined using immunohistochemistry and immunoelectron microscopy. Immunohistochemistry revealed that all three ES cell lines expressed ProGRP in a dot-like pattern in their cytoplasm, whereas SCLC cells showed a diffuse granular pattern. Immunoelectron microscopy revealed that ProGRP localized in neurosecretory granules (NSGs) in SCLC cells and in autolysosome-like structures in ES cells, with no NSGs observed in the ES cell lines. ES cells secrete high levels of ProGRP, similar to SCLC cells. However, in ES cells, ProGRP is localized in autolysosome-like structures, unlike the NSGs in SCLC, suggesting that ProGRP in ES can be transported and secreted without following the typical pathway for neuropeptides.

Mucoepidermoid carcinoma in the lung is uncommon, while the occurrence of a collision tumor consisting of primary mucoepidermoid carcinoma (MEC) and typical adenocarcinoma is extremely rare. We report a case of a 70-year-old female with the presence of a nodule in her right lung. The pathological examination revealed a primary collision tumor consisting of invasive adenocarcinoma and mucoepidermoid carcinoma. Manual microdissection was performed to selectively isolate the MEC and adenocarcinoma components, followed by exome sequencing which unveiled identical mutations in both components, suggesting their monoclonal origins with divergent differentiation. Clinical awareness and recognition of such collision tumors are crucial, as they will determine appropriate treatment strategies based on the individual biological aggressiveness of each tumor component.

The palmar plate is a crucial structural part of hand, associated with metacarpophalangeal and interphalangeal joints. Pediatric disorders involving the palmar plate of thumb metacarpophalangeal joint include trigger thumb, hyperextension, instability, and dislocation. While anatomical differences exist between children and adults, detailed microstructure evaluations in infants remain unexplored. In this study, we provide a histological and structural assessment of the previously unresolved microstructure of the palmar plate in the thumb metacarpophalangeal joint of infant Japanese macaques (Cercopithecidae, Macaca fuscata), a relevant model for human development. Histological staining (light microscopy) and scanning electron microscopy were employed to visualize the three-dimensional microstructure. The palmar plate of the infant macaque was found to contain (1) elastic fibers, (2) hyaline cartilage composed of type II collagen, and (3) type I collagen fibers arranged in distinct patterns. The cartilaginous region exhibited a reticulate fiber arrangement on its periphery, while the membranous region displayed dense and complex fibers on the proximal phalanx side and parallel on the metacarpal side, respectively. This is the first comprehensive three-dimensional investigation of the infant's thumb's palmar microanatomy, providing a foundation for understanding its development and implications for pediatric disorders.

Oncocytic sinonasal papilloma (OSP) is an uncommon, benign neoplasm characterized by papillary growths arising from the Schneiderian mucosa of the nasal and paranasal sinuses. OSP accounts for about 3-6% of all sinonasal papillomas (SPs), and clinically is often confused with inverted sinonasal papilloma (incidence 73%). Although SP shares some of the clinical characteristics of OSP, the pathogenesis differs and it is very important to distinguish between them. Here we present a case of OSP in the nasal and paranasal sinuses of a 67-year-old Japanese male, who complained of persistent left-sided nasal obstruction. A benign nasal paranasal tumor was diagnosed, and endoscopic sinus surgery was performed. Histopathologically, the tumor cells exhibited an exophytic and endophytic growth pattern, composed of multilayered eosinophilic columnar epithelium with finely granular cytoplasm, and forming microcysts filled with mucin or microabscesses. The epithelium was PTAH-positive, and showed positivity for cytokeratin-7 with oncocytic features. A review of the literature revealed 166 cases of OSP in the nasal and paranasal sinuses, with an overall recurrence rate of about 15%. Here we report a case of OSP in the nasal and paranasal sinuses for which PTAH staining specific for oncocytes was useful, together with a review of the relevant literature.

This study evaluates the effects of different high-intensity focused ultrasound irradiation (HIFU) methods on local tumor suppression and systemic antitumor effects, including the abscopal effect, in a mouse model of pancreatic cancer. To ascertain the efficacy of the treatment, pancreatic cancer cells were injected into the thighs of mice and HIFU was applied on one side using continuous waves or trigger pulse waves. Then, tumor volume, tissue changes, and immune marker levels were analyzed. Both the irradiation methods suppressed tumor growth, with the trigger pulse wave showing stronger effects and the difference being significant. Tumor suppression was also observed on the non-irradiated side, suggesting an abscopal effect. These effects vary depending on the irradiation method used. We conclude that HIFU induces both local tumor suppression and a systemic immune response, suggesting its potential for combination with immunotherapy for the treatment of pancreatic cancer.

To date, pagetoid spread-the proliferation of pagetoid cells in intraepidermal lesions, as observed in secondary extramammary Paget's disease-has not been reported in squamous epithelium derived from the extension of head and neck carcinomas. Herein, we report a case of pagetoid squamous cell proliferation associated with a primary intraosseous carcinoma (PIOC) arising in the periapical lesion of the maxilla, a finding not reported previously. A 60-year-old man presented with prostate adenocarcinoma and bilateral pubic bone, ilium bone, and sacral bone metastases. Radiological examination revealed a cyst that enveloped the apices of the left maxillary first molar roots. Histopathological examination of the cyst specimen indicated squamous cell carcinoma; hence, PIOC was suspected and partial left maxillectomy was performed. Histopathology results showed distant epitheliotrophic spread of atypical clear cells regarding the tumor. The epitheliotrophic cells were positive for cytokeratin (CK)19 and CK7 as odontogenic markers. These phenotypes were similar to those of tumor cells, suggesting pagetoid squamous cell proliferation associated with a PIOC arising. Although diagnosis of this condition is challenging, early detection is vital to ensure prompt treatment and improve patient prognosis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease involving the spine and bone joints, which is characterized by hyperosteogeny, ossification of ligaments, and ankylosis. Quercetin is a natural polyphenolic compound with various biological activities such as antioxidant, anti-inflammatory, and anti-tumor. It was to explore the effect of quercetin on AS ossification and its molecular mechanism. In vitro culture of AS mesenchymal stem cells was conducted. Cells were treated with 0, 10, 30, 60, and 80 μM quercetin, divided into control, 10 μM, 30 μM, 60 μM, and 80 μM groups. Alkaline phosphatase (ALP) staining, Alizarin Red staining, real-time quantitative polymerase chain reaction (qRT-PCR), and Western blot (WB) were employed to investigate the effect of quercetin on the expression of osteogenic-related genes and proteins. Additionally, bone morphogenetic protein (BMP) and Smad genes were knocked out to explore quercetin's regulation of BMP/Smad. In vivo experiments were conducted using 50 mice, including 10 in the normal group. An AS model was established in 36 mice, divided into negative control (n = 18, 0.9% saline) and quercetin groups (n = 18, quercetin). Safranin O-fast green (HE) staining and MicroCT scanning were performed before and 4 weeks after injection. In the 60 μM and 80 μM quercetin groups, ALP activity, Ca²⁺ deposition area, and relative protein/mRNA levels of BMP-1, BMP-2, Smad1, Smad4, and Smad5 in AS mesenchymal stem cells were significantly lower compared to the control, 10 μM, and 30 μM groups (P < 0.05). The 80 μM group exhibited lower levels than the 60 μM group (P < 0.05). In the siRNA + 80 μM group, the reduction in mRNA expression of BMP1, BMP2, Smad1, Smad4, and Smad5 was significantly greater compared to the siRNA group and the 80 μM group (P < 0.05). At 4 weeks post-injection, mice in the quercetin group showed significantly reduced severity of articular cartilage lesions, lymphocyte infiltration, and tissue edema, with no significant increase in sacroiliac joint fusion. Quercetin downregulates the expression of BMP and Smad-related proteins, inhibiting osteogenic differentiation of AS mesenchymal stem cells and effectively reducing ALP activity and Ca²⁺ deposition levels. These findings suggest that quercetin holds potential application value in the control and treatment of AS disease.

Helicobacter pylori possesses an intrabacterial nanotransportation system (ibNoTS) for transporting VacA, CagA, and urease within the bacterial cytoplasm. This system is controlled by the extrabacterial environment. The transport routes of the system for VacA have not yet been studied in detail. In this study, we demonstrated by immunoelectron microscopy that VacA localizes closely with the MreB filament in the bacterium, and the MreB polymerization inhibitor A22 obstructs the transport of VacA by ibNoTS. These findings indicate that the route of ibNoTS for VacA is closely associated with the MreB filament Additionally, it was confirmed that VacA does not closely associate with the bacterial filament FtsZ, which is involved in the transport of the virulence factor urease, as previously suggested. We propose that the route of ibNoTS for VacA is associated with the MreB filament in H. pylori.