Background/aim: Nicotinamide N-methyltransferase (NNMT) is an enzyme that is overexpressed in malignancies. NNMT expression has not been previously studied in endometrial cancer (EC). Increased phospho-Akt (pAkt) levels in response to NNMT overexpression have been reported in in vitro studies of different cancer types. We assayed NNMT expression in primary and metastatic high-grade EC and investigated the relationship of NNMT with p53, pAkt, and survival. Materials and methods: NNMT, pAkt, and p53 expressions were assayed in 100 tissue samples of benign endometria, primary EC, and metastatic EC by immunohistochemistry. Results: The NNMT immunoreactivity score was significantly higher in primary high-grade EC than benign endometrial tissue (P = 0.001). NNMT expression in metastatic tissue was significantly higher than in primary cancer (P < 0.001). Metastatic stromal NNMT expression was significantly higher than that of the adjacent tumor and stroma adjacent to the primary tumor. p53 expression in the primary tumor showed a significant positive correlation with omental NNMT and pAkt expression. NNMT expression was also correlated with pAkt expression in metastatic tissue. NNMT overexpression in metastatic tissue was associated with decreased survival (P = 0.039). Conclusion: This study suggests that NNMT may promote cancer progression and that NNMT overexpression is associated with aberrant p53 expression, pAkt, and poor survival. NNMT's role in cancer progression could make it a target of EC therapy.
Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme, overexpressed in various human malignancies. It is associated with cancer progression and resistance to treatment. The role of NNMT in cervical cancer has not been studied thus far. We aimed to evaluate expression of NNMT in cervical squamous cell carcinoma (SCC) and investigate its clinical significance. NNMT expression was assayed by use of immunohistochemistry in 61 cases of SCC, 11 cases of high-grade squamous intraepithelial lesion, 17 cases of low-grade squamous intraepithelial lesion, and 51 benign cervical tissues. NNMT immunoreactivity was scored based on staining intensity and percentage of positively stained cells. The expression of NNMT was significantly higher in SCC than in benign tissue, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion (P<0.001). NNMT expression in benign tissue was significantly lower than in low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. When stratified according to stage, NNMT expression was significantly higher in patients with stage III and IV than those in stage I and II disease (P=0.009). For all stages, patients with metastatic pelvic or para-aortic lymph nodes had significantly higher NNMT expression than patients without nodal involvement (P=0.001). Although preliminary, this is the first study to detect overexpression of NNMT in SCC and increased expression associated with advanced stage and metastatic lymph nodes. NNMT should be investigated further in cervical cancer as a potential therapeutic target and a prognostic indicator.
Background Radiotherapy (RT) involves the use of ionizing radiation in treating malignancies and benign disorders. However, RT damages target and healthy surrounding tissues in a dose-dependent manner. This effectively reduces patient compliance and quality of life, thereby warranting the prevention of RT-induced adverse effects on skin. Adipose-derived stem cells (ASCs) are used to treat RT-induced damage and platelet-rich plasma (PRP) provides a scaffold that potentiates the effects of ASCs. Thus, the aim of this study was to determine the mechanism employed by ASCs and PRP in protecting against RT-induced adverse effects. Methods We have established an immunodeficient mouse transplantation model using which human hair follicular units were implanted. When the follicular units were macroscopically and microscopically mature and anagenic, we administered localized RT. Subsequently, the mice were randomly divided into 4 groups based on the subcutaneous injection of the following to the irradiated transplantation site: saline, PRP, ASCs, and a combination of ASCs and PRP. Next, we used macroscopic and microscopic analyses to determine the protective effects of the injected solutions on skin and hair follicles. Results Adipose-derived stem cells reduced RT-induced adverse effects, such as impaired wound healing, alopecia, skin atrophy, and fibrosis by suppressing inflammation, dystrophy, degeneration, connective tissue synthesis, and apoptosis and increasing cellular proliferation, differentiation, and signaling. Moreover, these effects were augmented by PRP. Conclusions Thus, co-administering ASCs with PRP in mice prevented RT-induced adverse effects and can be tested for use in clinical practice.
Simultaneous calcified fibrous pseudotumor (CFT) and Castleman disease (CD) is an extremely rare association. CD is an uncommon lymphoproliferative disease that can arise in various sites of the body, while CFT is a rare type of benign fibrous lesion that frequently affects children and young adults, occurring as solitary or multiple lesions throughout the human body. Both entities are rare and exhibit typical and diverse histomorphological features. We report the case of a 15-year-old female patient, who, at the age of 13 had a biopsy performed at an external medical center; however, after 4 months the lesion had regrown. This lesion was removed with a surgical operation; however, it regrew 2 years later and was removed a third time. The results of the latter two biopsies were the same: CFT accompanying CD. The histologic examination of the excised lymph node and the surrounding tissue showed hyalinized fibrous tissue containing dystrophic and psammomatous calcification. In this case, the hyaline vascular type of CD was found to be intertwined with a CFT, which hampered the differentiation of whether both entities emerged within the lymph node or if the CFT developed from the soft tissue and then involved the lymph node. Future studies involving larger case series will provide a more precise insight, which should serve to resolve the current uncertainty.
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