Effect of Artemisia species on cellular proliferation and apoptosis in human breast cancer cells via estrogen receptor-related pathway

Objective

To investigate the mechanism underlying the anticancer effect of Artemisia species through the inhibition of cell growth and induction of apoptosis in breast carcinoma cells.

Methods

To evaluate the anticancer activity of methanol extracts of eight Artemisia species (Artemisia stolonifera, Artemisia selengensis, Artemisia japonica, Artemisia Montana, Artemisia capillaris, Artemisia sylvatica, Artemisia keiskeana, and Artemisia scoparia), we first investigated the proliferation of estrogen receptor (ER)-positive MCF-7 breast carcinoma cells exposed to 5 or 200 g/mL for 72 h. Apoptosis induction was assessed by an Annexin V binding assay in cells exposed to extracts at a high concentration (200 g/mL). To verify the mechanism of apoptosis, ER expression and its related signaling was investigated using an immunoblot assay under the same conditions.

Results

MCF-7 cells showed the strongest antiproliferative response to the tested extracts. However, a biphasic effect was observed: the extracts inhibited proliferation at high concentrations whereas they stimulated it at low ones. ER expression was similarly modulated by the extracts. However, all of the extracts induced apoptosis at a high concentration (200 g/mL). Compared to the control level, exposure to the extracts resulted in a remarkable increase in the shift of cell populations.

Conclusion

The present study suggests that the tested Artemisia species exerted their anticancer effects through the induction of apoptosis via an ER-related pathway.     

A cyclohexanonyl bromophenol from the red alga Symphyocladia latiuscula

From an extract of the red alga Symphyocladia latiuscula, a bromophenol (1) was isolated and characterized as (2R)-2-(2,3, 6-tribromo-4,5-dihydroxybenzyl)-cyclohexanone based on the spectroscopic evidence. The bromophenol was found to be a scavenger of 1,1-diphenyl-2-picrylhydrazyl radical.     

Prospective evaluation of the efficacy of peroral endoscopic myotomy in patients with achalasia

Peroral endoscopic myotomy (POEM) is an endoscopic alternative to surgical myotomy in patients with achalasia. This study aimed to evaluate the efficacy and clinical outcomes of POEM.A total of 20 patients with achalasia who underwent POEM between October 2016 and November 2017 were prospectively recruited. The intraoperative esophagogastric junction distensibility index (mm²/mm Hg) was measured pre- and post-myotomy using an endoluminal functional lumen imaging probe. Clinical response was defined as Eckardt score ≤3. Health-related quality of life was measured by the 36-item short-form health survey score.POEM was successfully completed in all cases. The median procedure time was 68.5 minutes (range 50.0–120.0), and the median myotomy length was 13 cm (range 11–18). Major adverse events were encountered in 2 cases. Overall, clinical responses were observed in all patients during a median follow-up of 11.9 months (range 1.2–26.2). Postoperative esophagogastric junction distensibility index was significantly higher than baseline (from 1.3 [range 0.8–6.9] to 6.3 [range 25–19.2], P < .001). The median Eckardt scores were decreased after POEM (5 [range 2–11] to 1 [range 0–3], P < .001), and the 36-item short-form health survey score was also improved significantly after POEM (67.5 [range 34.5–93.9] to 85.7 [range 53.4–93.3], P = .004).POEM is an effective treatment for achalasia, based on the improvement of both symptoms and objective measures.Clinicaltrial.gov {"type":"clinical-trial","attrs":{"text":"NCT 02989883","term_id":"NCT02989883"}}NCT 02989883     

Localized esophageal ulcerations after CyberKnife treatment for metastatic hepatic tumor of colon cancer.

CyberKnife is an image-guided robotic system designed for stereotactic radiosurgery. It uses the combination of robotics and image guidance to deliver concentrated and accurate beams of radiation to intracranial and extracranial targets. Although the frameless nature of the CyberKnife allows tumors in the chest and abdomen to be treated as well, complications associated with CyberKnife treatment have not been established yet due to its short clinical experience. We describe a case of localized esophageal ulcerations after CyberKnife treatment for metastatic hepatic tumor of colon cancer.     

A case of splenic pseudocyst difficult to differentiate from splenic lymphangioma]

Splenic pseudocyst is a rare complication of abdominal trauma. Although it is rare, splenic pseudocyst is well-documented in the literature. According to the current classification, approximately 30% of all splenic cysts or pseudocysts result from direct abdominal trauma. In addition, chronic pancreatitis leads to change of nearby organs with possible acute and chronic complications including splenic lesions. This unusual complication can occur in both emergent and non-emergent conditions. The useful diagnostic procedures to assess intrasplenic pseudocyst are sonogram, CT scan, splenic scan, and occasionally angiography. However, definite diagnosis of pseudocyst is possible only after splenectomy when the absence of epithelial lining is confirmed histologically. Splenic pseudocyst requires surgical resection. We experienced a 31-year-old man who confirmed of warmness in the left side of back with left upper quadrant abdominal pain for several months. First impression was splenic lymphangioma based on CT scan and sonogram finding. Splenectomy was performed. Microscopic examination revealed splenic pseudocyst with fibrous capsule without epithelial lining.     

Autonomic nerve stimulation reverses ventricular repolarization sequence in rabbit hearts

Sympathetic activity and spatial dispersion of repolarization (DOR) have been implicated as mechanisms that promote arrhythmia vulnerability; yet there are no direct measurements of the effects of autonomic nerve stimulation on DOR. Rabbit hearts were perfused in a Langendorff apparatus with full sympathetic and parasympathetic innervation and were optically mapped to measure action potential durations and DOR (apex-base) over the left ventricles. DOR was measured under sinus rhythm, during bilateral sympathetic nerve stimulation (SNS) and right and/or left vagus nerve stimulation and was compared with DOR during isoproterenol (100 nmol/L) or acetylcholine (1 micromol/L) infusion. In sinus rhythm, repolarization started at the apex and systematically progressed toward the base. SNS (10 to 15 Hz) increased DOR by 29% (from Deltaaction potential duration=17+/-0.7 to -22+/-1.6 ms, n=6) and reversed DOR as the direction of repolarization from apex-->base in sinus rhythm shifted to base-->apex in 5 to 15 seconds after SNS. DOR flipped back to its sinus rhythm DOR pattern 115+/-15 seconds after the interruption of SNS. During right or left vagus nerve stimulation, there was no change in the direction of DOR, but bilateral vagus nerve stimulation increased and reversed DOR to base-->apex direction. Infusion of isoproterenol or acetylcholine increased DOR but did not alter the direction of repolarization sequences. These findings demonstrate that bilateral autonomic activity (SNS or vagus nerve stimulation) cause reversible shifts of apex-base DOR and that the spatial heterogeneities of autonomic effects on the ventricles are most likely attributable to a greater innervation at the base than the apex of the heart.     

Long-term growth of pediatric patients following living-donor liver transplantation

In order to determine the influence of living donor liver transplantation (LDLT) on long-term growth, we studied the progress of 36 children who had survived more than 5 yr after LDLT from 1994 to 1999. The median age at the transplantation was 1.5 yr (range: 6 months-15 yr) and the median follow-up period was 6.5 yr (range: 5-9 yr). A height standard deviation score (zH) was analyzed for each patient according to medical records. Significant catch-up growth occurred within 2 yr after LDLT with a mean zH changing from -1.2 to 0.0 and was maintained for up to 7 yr post-transplantation (zH-0.1). Younger children (<2 yr) were more growth-retarded at the time of LDLT, but showed higher catch-up growth rates and their final zH was greater than that of older children. Children with liver cirrhosis were more growth-retarded at the time of LDLT, but showed significant catch-up growth and their final height was similar to children with fulminant hepatitis. Growth in children who experienced significant hepatic dysfunction after LDLT was not significantly different from those without graft dysfunction. There was no difference between the types of immunosuppressants used. Our finding suggests that LDLT can result in adequate catchup linear growth, and this effect can persist even after 7 yr post-transplantation.     

Relationships of lead, copper, zinc, and cadmium levels versus hematopoiesis and iron parameters in healthy adolescents

To investigate the relationships of trace element concentrations vs hematopoiesis and iron parameters, we measured lead, copper, zinc, cadmium, and ferritin levels in 251 healthy adolescents. Concentrations of trace metals were determined by atomic absorption spectrophotometry. There were no significant gender-related differences in serum copper or serum cadmium concentrations. However, blood lead and serum zinc levels were significantly higher in males than females (3.82+/- 1.24 and 118.4 +/- 43.7 microg/dl vs 2.86+/- 1.06 and 83.5+/- 35.2 microg/dl, p<0.05, respectively). Subjects with elevated lead and copper concentrations exhibited significantly higher leukocyte counts and significantly lower serum iron levels than those with decreased lead and copper concentrations, but no significant differences were observed in blood erythrocyte counts or hemoglobin levels between the 2 groups. Blood lead concentrations were 2-fold higher in male adolescents with leukocytes >9.1 x 10(3)/microl than in those with leukocytes <4.3 x 10(3)/microl (5.04+/- 1.67 microg/dl vs 2.51+/- 0.75 microg/dl, p<0.05). Leukocyte counts had significant correlations with blood lead (r=0.39, p<0.05) and serum copper (r=0.26, p<0.05) in males and zinc (r=0.28, p <0.05) in females. Serum iron levels were inversely correlated with blood lead and serum copper concentrations but were not correlated with serum zinc or cadmium levels. In short, blood lead and serum copper concentrations have important relationships to leukocyte counts and iron parameters in adolescents.     

A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable,advanced hepatocellular carcinoma

Background/Aims

Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC.

Methods

The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m² on days 1~3) and cisplatin (60 mg/m² on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks.

Results

Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group.

Conclusions

High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.