Humans ; Osteogenesis ; Mesentery/surgery* ; Ossification, Heterotopic/surgery*

BACKGROUNDEpidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health.

METHODSSix-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test.

RESULTSUrine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.

CONCLUSIONAngiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; pathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Losartan ; therapeutic use ; Male ; Orchiectomy ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole ; drug effects

OBJECTIVETo investigate the underlying mechanism of apoptosis-inducing effect of a specific COX-2 inhibitor SC236 in gastric cancer cells.

METHODSWestern blot analysis was used to measure apoptosis-related proteins, cytochrome c, and caspase-3. The catalytic activity of the caspases was measured using a colorimetric assay.

RESULTSTreatment of AGS gastric cancer cells with SC236 caused a significant elevation of the pro-apoptotic protein Bak, release of cytochrome c to the cytosol, and activation of caspase-3. A specific caspase-3 inhibitor, z-DEVD-fmk, blocked SC236-induced apoptosis.

CONCLUSIONSC236 inhibits cell growth and induces apoptosis in gastric cancer cells at least partly through the up-regulation of Bak, stimulation of cytochrome c release, and activation of caspase-3.

Adenocarcinoma ; metabolism ; pathology ; Apoptosis ; drug effects ; Caspase 3 ; Caspases ; metabolism ; Cell Line, Tumor ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Cytochromes c ; metabolism ; Humans ; Oligopeptides ; pharmacology ; Poly(ADP-ribose) Polymerases ; metabolism ; Pyrazoles ; pharmacology ; Stomach Neoplasms ; metabolism ; pathology ; Sulfonamides ; pharmacology ; bcl-2 Homologous Antagonist-Killer Protein ; metabolism

China ; Coal Mining ; Humans ; Pneumoconiosis ; Quality of Life ; Surveys and Questionnaires ; Transients and Migrants

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.
Male ; Humans ; Female ; Biomarkers, Tumor/analysis* ; Gastrointestinal Neoplasms/pathology* ; S100 Proteins/analysis* ; Melanoma

OBJECTIVETo observe the effect of rosiglitazone (RGZ) and all-trans-retinoic acid (ATRA) on the growth of myeloma xenograft in nude mice and to explore the influence of RGZ and ATRA on VEGF expression and angiogenesis in the tumor.

METHODSVEGF gene expression in myeloma cell line U266 cells was analyzed by semi-quantitative RT-PCR after incubation with RGZ, ATRA, or RGZ + ATRA for 24 h. Myeloma xenograft was established by subcutaneous injection of 10(7) U266 cells in the scapula area of 4-week old nude mice. 7 days later, the nude mice were administered with RGZ, ATRA or RGZ + ATRA, respectively, by intraperitoneal injection once every day for 21 days. The control mice were given equal volume of normal saline instead of the drug. On the 21(st) day of treatment, the mice were sacrificed and the tumors were taken off, and the tumor volume and weight were measured. The tumors were examined by histopathology with HE staining, and microvessel density (MVD), CD34 and VEGF expression in the tumors were analyzed by immunohistochemical staining.

RESULTSVEGF mRNA was highly expressed in U266 cells and was decreased in a dose-dependent manner after incubation with RGZ. The VEGF mRNA level was further more decreased after RGZ + ATRA treatment. Xenografts of U266 cells were developed in all nude mice. The volume and weight of xenografts in the RGZ group were (785 ± 262) mm(3) and (1748 ± 365) mg, respectively, significantly lower than those of the control group (both P < 0.01). More significant inhibition was in the RGZ + ATRA group, (154 ± 89) mm(3) and (626 ± 102) mg, respectively, both were P < 0.05 vs. the RGZ group. RGZ inhibited the angiogenesis in U266 xenografts and immunohistochemical staining showed that the tumor MVD and VEGF expression were significantly decreased by RGZ treatment, and further more inhibited in the RGZ + ATRA group. VEGF protein was expressed in all xenografts in the nude mice. Its immunohistochemical staining intensity was 2.20 ± 0.40 in the control group, significantly higher than that of 1.48 ± 0.37 in the RGZ group (P < 0.01), and that of RGZ + ATRA group was 0.58 ± 0.26, further significantly lower than that of the RGZ group (P < 0.01). CD34 was expressed in all xenografts, most highly in the control group and lowest in the RGZ + ATRA group. The microvessel density (MVD) was highest in the control group (56.4 ± 15.2), significantly lower in the RGZ group (44.6 ± 11.2) (P < 0.05), and lowest in the RGZ + ATRA group (21.5 ± 8.6, P < 0.01).

CONCLUSIONSThe growth of myeloma cells can also be inhibited by RGZ and ATRA in nude mice in vivo. In addition to differentiation and apoptosis induction, RGZ can inhibit the formation of myeloma xenograft probably also through the downregulation of VEGF expression and subsequent angiogenesis.

Animals ; Antigens, CD34 ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Transplantation ; Neovascularization, Pathologic ; RNA, Messenger ; metabolism ; Thiazolidinediones ; administration & dosage ; pharmacology ; Tretinoin ; pharmacology ; Tumor Burden ; drug effects ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Xenograft Model Antitumor Assays

INTRODUCTIONTraditional Chinese medicine (TCM) has been used as an alternative in treating children with atopic dermatitis (AD) but its efficacy and potential side effects are debatable. We recently used a TCM capsule (PentaHerbs) on 9 children and observed significant reductions in clinical scores of disease severity. However, there have been concerns that the therapeutic effects of many forms of TCM are due to the presence of corticosteroids. The purpose of this study was to evaluate if common corticosteroids are present in PentaHerbs capsules.

MATERIALS AND METHODSPentaHerbs powder was analysed with thin-layer chromatography, infra-red spectrophotometry and liquid chromatography mass spectrometry.

RESULTSHydrocortisone, prednisolone, fludrocortisone and dexamethasone were not detected in the PentaHerbs capsules.

CONCLUSIONCorticosteroids are not present in the 5 familiar herbs that were earlier shown to have efficacy on AD.

Child ; Chromatography, Thin Layer ; Dermatitis, Atopic ; drug therapy ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Glucocorticoids ; analysis ; therapeutic use ; Humans ; Mass Spectrometry ; Pilot Projects ; Spectrophotometry, Infrared

Objective: To investigate the clinicopathological characteristics, pathological diagnosis of Ewing's sarcoma of the central nervous system. Methods: Six cases of Ewing's sarcoma of the central nervous system diagnosed at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from 2015 to 2022 were collected. The clinical manifestations, histological morphology, immunophenotype and molecular genetics of these cases were analyzed. The related literature was reviewed. Results: There were four males and two females, with a male to female ratio of 2∶1. The onset age was 17-40 years, with a median age of 23 years. All 6 tumors were located in the spinal cord (2 cases of cervical vertebra, 1 case of thoracic vertebra, 2 cases of lumbar vertebra, and 1 case of sacral vertebra). The patients' clinical manifestations were mostly lumbago, weakness and numbness of lower limbs/limbs. In 1 case, the tumor recurred and metastasized to the suprasellar region and the third ventricle. Microscopically, the tumor showed diffuse infiltrative growth. In some cases, the tumor was closely related to the spinal meninges. The tumor cells were arranged in sheet, lobular, thin-rope, and nest-like patterns. Homer-Wright rosette was visible. The tumor cells were small to medium in size, and most of them had scant cytoplasm. A few cells had clear cytoplasm. Some areas were rhabdoid. The tumor cell nuclei showed focal mild pleomorphism. The chromatin was uniform and delicate while the nucleoli were not obvious. Mitosis was commonly seen. The tumor was separated by fibrous connective tissue and may be accompanied by mucinous degeneration. Immunohistochemistry showed that all tumors were positive for CD99, NKX2.2, Fli1, ERG. ATRX, H3K27me3, INI1 and BRG1 were all retained. Immunohistochemical stains for EMA, GFAP and Olig2 were negative. The Ki-67 proliferation index was 30%-70%. EWSR1 break-apart FISH test was positive. Conclusions: Ewing's sarcoma is rare in the central nervous system and needs to be distinguished from a variety of neoplasms with primitive undifferentiated small cell morphology. Immunohistochemistry and molecular genetics may be required for a proper diagnosis.
Humans ; Male ; Female ; Young Adult ; Adult ; Adolescent ; Sarcoma, Ewing/pathology* ; Proto-Oncogene Protein c-fli-1 ; Immunohistochemistry ; Biomarkers, Tumor/genetics* ; Central Nervous System/pathology*