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The correlations of murine double minute 2 ( MDM2) T309 G and esophageal cancer were elucidated because the association between MDM2 expression states and clinicopathological parameters of esophageal squamous cell carcinoma ( ESCC) is controversial. We conducted a meta-analysis on studies screened from Pub Med, Web of Science, Embase, the Cochrane Library, and the Chinese Biomedical Literature Databases that were published before October 2014. All studies describing the association between MDM2 and ESCC were traced. Meta-analysis was performed using the STATA software ( Stata Corp., College Station, TX, USA). A total of 9 studies with 707 cases and 324 controls were included. MDM2 expression was higher in ESCC than in normal esophageal epithelium (odds ratio [ OR] 10.38, 95% confidence interval [ CI] 6.42-16.78, P < 0.001). High MDM2 expression was associated with early primary tumor stage ( T1/ T2 vs. T3/ T4, OR 0.59, 95% CI 0.38-0.92, P = 0.018) and increased risk of regional lymph node metastasis ( N0 vs. N1, OR 1.66, 95% CI 1.03-2.67, P = 0.039). However, no relationship was observed between MDM2 expression and the risk of distant metastasis ( OR = 2.09, 95% CI 1.00-4.36, P = 0.050), and MDM2 was not significantly correlated with TP53 expression ( OR 1.22, 95% CI 0.53-2.77, P = 0.643). Our analysis suggests that MDM2 acts as a potent marker of early primary tumor stage but higher risk of regional lymph node metastasis in ESCC. However, because of the limited number of studies included, the result should be further clarified by well-designed prospective studies. [ABSTRACT FROM AUTHOR]

Protein kinase D1 ( PRKD1) is a kinase that regulates various pathways, which involve in cell proliferation, apoptosis, cell adhesion and invasion. Although PRKD1 expression has been observed in many cancers, its role in esophageal squamous cell cancer ( ESCC) has not been well reported. As its dysregulation in cancers is organ specific, we sought to investigate the potential role of PRKD1 in the progression of ESCC. Samples were collected from 178 patients with completely resected ESCCs at Sun Yat-sen University Cancer Center, including 47 pairs of tumorous and non-tumorous tissues. PRKD1 mRNA expression was investigated by quantitative real-time polymerase chain reaction. Receiver operating characteristic ( ROC) curve analysis was used to search for a feasible cut-off point of PRKD1 mRNA levels for predicting cancer-specific survival. Kaplan- Meier and multivariate Cox regression analysis were used to assess the prognostic value of PRKD1 mRNA level in ESCC patients. In result, upregulation of PRKD1 mRNA was detected in 55.3% (26/47) of ESCC tissues compared with paired non-tumorous ones ( P = 0.011). ROC analysis indicated 3.28 as a cut-off point, and thus 72 and 106 tumors with low and high PRKD1 mRNA expression were categorized. High- PRKD1 mRNA expression in tumors appeared with more frequency in heavy smokers ( P = 0.002) and patients with advanced pathological T category ( P = 0.034). Kaplan- Meier analysis indicated that patients with low- PRKD1 mRNA had a longer cancer-specific survival than the ones with high- PRKD1 level ( P = 0.044). Multivariate analysis showed that tumorous PRKD1 mRNA expression was an independent prognostic factor (hazard ratio: 1.538, 95% confidence interval: 1.018-2.323, P = 0.041) in resected ESCC. Subgroup analysis revealed that the discernibility of PRKD1 mRNA level on ESCC outcomes was only pronounced in heavy smokers ( P = 0.002), but not in non-heavy smokers ( P = 0.870). PRKD1 might play a potential oncogenic role in ESCC. It might be an independent biomarker to predict prognosis in heavy smokers with ESCC. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to determine whether there are differences in clinical and radiographic outcomes among three different stem designs for subtrochanteric osteotomy in Crowe type IV developmental dysplasia of the hip (DDH)., Methods: A retrospective analysis of prospectively collected data was undertaken from a consecutive series of 37 Crowe type IV DDHs treatment of noncemented total hip arthroplasty with chevron subtrochanteric osteotomy in 30 patients. Patients are divided into three groups, including Ribbed group (using Link Ribbed stem; n = 14), Synergy group (using Synergy stem; n = 9), and Link Classic Uncemented (LCU) group (using LCU stem; n = 14), according to the design of the stem. The clinical and radiographic outcomes were evaluated., Results: All patients were followed for 36 months. The time of bone union of the LCU stem was significantly longer than that of the Synergy stem (P = 0.02) and the Ribbed stem (P > 0.05); the time of bone union of the Ribbed stem was longer than that of the Synergy stem (P > 0.05). The length of stem in the distal femur of the Ribbed stem (P = 0.000) and the Synergy stem (P = 0.001) is significantly longer than that of the LCU stem. There were three hips with malunion, stem loosening, and varus alignment, which were observed in the LCU stem. None of these were observed in Ribbed and Synergy stems. In total hip arthroplasty with a noncemented stem combined with subtrochanteric femoral osteotomy for Crowe IV DDH, 89.2% hips (33/37) can achieve good and excellent clinical outcomes. There were three hips (1 hip in the Ribbed stem and two in the LCU stem) with fair clinical outcomes and one hip (LCU stem) with poor clinical outcomes., Conclusions: Although Ribbed, Synergy, and LCU stems have similar clinical outcomes, the LCU stem has a tendency to a varus position, longer union time, malunion, and stem loosening, when compared with the Ribbed and Synergy stems. We recommend against adoption of the LCU stem for Crowe IV DDH with subtrochanteric femoral osteotomy., Level of Evidence: Level III, therapeutic study., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

A slight induction of granulocytic differentiation of HL-60 cells occurred after treatment with antileukemia chemotherapeutic agents Adriamycin (ADM) and daunomycin (DM). Addition of an inhibitor (sphinganine, SP) of protein kinase C (PKC) enhanced 2-4-fold the ADM or DM-induced differentiation. This phenomenon was accompanied by a slightly augmented antiproliferative effect. The enhancement of differentiation induction in these treatments seemed to be absolute, since the combination treatment (ADM-SP or DM-SP) showed about 2.5-3.6 times as many differentiated cells as the treatment with the anticancer drugs ADM or DM alone. Further characterization of the interaction of ADM and DM with SP on differentiation of HL-60 cells was carried out. Whereas the addition of SP in the fresh medium after the removal of ADM or DM (0.5 h treatment) enhanced the induction of differentiation, a pretreatment (24 h) of the cells with SP followed by continuous exposure to ADM or DM did not show such enhancement effect. The addition of SP at as late as 48 h after the administration of ADM or DM potentiated the induction of differentiation to the same extent as in the simultaneous combination of ADM-SP or DM-SP. Similar results were obtained in the experiments with another PKC inhibitor, staurosporine. These results indicated that inhibition of PKC activities may play an important role in the later events during the induction of differentiation elicited by ADM or DM. The use of the antileukemia drugs ADM and DM in combination with an inhibition of PKC activity results in enhancement of induction of differentiation and suggests a new strategy and a promising approach to the treatment of leukemia.

Dipyridamole (DPM) enhanced sensitivity to doxorubicin (DOX) in a human leukemia cell line that was already relatively sensitive to this agent. Using an immunofluorescence technique, we determined the localization of nucleophosmin (protein B23) in HL-60 cells after incubation with DOX in the absence and presence of DPM. Bright nucleolar fluorescence was observed in control HL-60 cells. The addition of DOX (0.1-0.25 micrograms/ml) in the culture system resulted in time- and dose-dependent induction of nucleophosmin translocation from the nucleolus to nucleoplasm and inhibition of cell growth. DPM (5 microM) alone had no effect on nucleophosmin translocation and inhibition of cell growth. However, the addition of DPM to the cells enhanced DOX-stimulated translocation of nucleophosmin. There was a good correlation between the DPM enhancement of DOX-induced nucleophosmin translocation and the increased inhibition of cell growth. The cell number decreased to a greater extent within a shorter time period under treatment with DOX in the presence of DPM. Short exposure (0.5 hr) of HL-60 cells to DOX induced dose-response nucleophosmin translocation and cell growth inhibition. Such effects of a short exposure to DOX were also enhanced by DPM (5 microM) included in the fresh medium after removal of DOX. This was in agreement with the observation that DPM could increase the cellular DOX by inhibiting the drug efflux from the cells. These results demonstrate that DPM, being able to increase and retain the intracellular levels of DOX, can markedly enhance the cytotoxicity of DOX, and suggest possible clinical application. "Nucleophosmin translocation", as observed by immunofluorescence, could be useful in determining the efficacy of combinations of DOX and DPM in cancer chemotherapy.