Portulacerebroside A inhibits adhesion, migration, and invasion of human leukemia HL60 cells and U937 cells through the regulation of p38/JNK signaling pathway

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Recoverable, Record-High Lactic Acidosis in a Patient with Glycogen Storage Disease Type 1: A Mixed Type A and Type B Lactate Disorder

A 17-year-old patient with GSD type 1a (von Gierke disease) was hospitalized with an extremely elevated serum lactate following an intercurrent infection and interruption of his frequent intake of carbohydrates. The patient developed shock, oliguric renal failure, and cardiorespiratory failure requiring mechanical ventilation and inotropes. At the peak of metabolic decompensation and clinical instability, serum lactate reached a level of 47.6 mmol/L which was accompanied by a severe anion gap metabolic acidosis with a pH of 6.8 and bicarbonate of 4 meq/L. The patient was stabilized with massive infusions of sodium bicarbonate (45 meq/h) and glucose and recovered without the need for dialysis. This patient illustrates pathophysiologic mechanisms involved in the development of extreme mixed type A and type B lactic acidemia, reflecting altered metabolic pathways in GSD type 1, combined with tissue hypoperfusion. The rationale for the specific interventions in this case is outlined.

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Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer

Abstract

Background

miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and mechanism remain largely unknown. This study is aimed to study the role of miR-501-5p in the progression of gastric cancer.

Methods

Real-time PCR analysis was used to determine miR-501-5p expression in gastric cancer cell lines, clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. The role of miR-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. Luciferase reporter assay, cellular fractionation and western blot analysis were used to determined that miR-501-5p activated the wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β.

Results

Herein, our results revealed that miR-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. High miR-501-5p levels predicted poor overall survival in gastric cancer patients. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. Notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress miR-501-5p, and mediated miR-501-5p-induced cancer stem cell-like phenotype. Furthermore, miR-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade, including DKK1, NKD1 and GSK3β. These results demonstrate that miR-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β, which promotes gastric cancer stem cell like phenotype.

Conclusions

Taken together, our findings reveal a new regulatory mechanism of miR-501-5p and suggest that miR-501-5p might be a potential target in gastric cancer therapy.

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Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer

Abstract

Background

miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological role and mechanism remain largely unknown. This study is aimed to study the role of miR-501-5p in the progression of gastric cancer.

Methods

Real-time PCR analysis was used to determine miR-501-5p expression in gastric cancer cell lines, clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. The role of miR-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. Luciferase reporter assay, cellular fractionation and western blot analysis were used to determined that miR-501-5p activated the wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β.

Results

Herein, our results revealed that miR-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. High miR-501-5p levels predicted poor overall survival in gastric cancer patients. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. Notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress miR-501-5p, and mediated miR-501-5p-induced cancer stem cell-like phenotype. Furthermore, miR-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade, including DKK1, NKD1 and GSK3β. These results demonstrate that miR-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β, which promotes gastric cancer stem cell like phenotype.

Conclusions

Taken together, our findings reveal a new regulatory mechanism of miR-501-5p and suggest that miR-501-5p might be a potential target in gastric cancer therapy.

http://ift.tt/2fUSTX3

Intensity-Modulated Radiation Therapy Improves the Target Coverage Over 3-D Planning While Meeting Lung Tolerance Doses for All Patients With Malignant Pleural Mesothelioma

Purpose:

To investigate high conformality on target coverage and the ability on creating strict lung dose limitation of intensity-modulated radiation therapy in malignant pleural mesothelioma.

Patients and Methods:

Twenty-four radiation therapy plannings were evaluated and compared with dosimetric outcomes of conformal radiation therapy and intensity-modulated radiation therapy. Hemithoracal radiation therapy was performed on 12 patients with a fraction of 1.8 Gy to a total dose of 50.4 Gy. All organs at risk were contoured. Radiotherapy plannings were differed according to the technique; conformal radiation therapy was planned with conventionally combined photon–electron fields, and intensity-modulated radiation therapy was planned with 7 to 9 radiation beam angles optimized in inverse planning. Strict dose–volume constraints were applied.

Results:

Intensity-modulated radiation therapy was statistically superior in target coverage and dose homogeneity (intensity-modulated radiation therapy-planning target volume 95 mean 100%; 3-dimensional conformal radiation therapy-planning target volume 95 mean 71.29%, P = .0001; intensity-modulated radiation therapy-planning target volume 105 mean 11.14%; 3-dimensional conformal radiation therapy-planning target volume 105 mean 35.69%, P = .001). The dosimetric results of the remaining lung was below the limitations on intensity-modulated radiation therapy planning data (intensity-modulated radiation therapy-lung mean dose mean 7.5 [range: 5.6%-8.5%]; intensity-modulated radiation therapy-lung V5 mean 55.55% [range: 47%-59.9%]; intensity-modulated radiation therapy-lung V20 mean 4.5% [range: 0.5%-9.5%]; intensity-modulated radiation therapy-lung V13 mean 13.43% [range: 4.2%-22.9%]).

Conclusion:

With a complex and large target volume of malignant pleural mesothelioma, intensity-modulated radiation therapy has the ability to deliver efficient tumoricidal radiation dose within the safe dose limits of the remaining lung tissue.

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Alveolar echinococcosis of the right adrenal gland: a case report and review of the literature

Extrahepatic manifestations of Echinococcus multilocularis are very rare, especially in the adrenal glands. To the best of our knowledge, only seven cases of adrenal alveolar echinococcosis have been reported, al...

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Hysteroscopic management of a heterotopic pregnancy following uterine artery embolization: a case report

Intra-uterine pregnancy coexisting with cervical pregnancy (heterotopic pregnancy) is a rare condition and its management is challenging because of the massive bleeding associated with cervical pregnancy. Uter...

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