Potential Implications of Changing Photosynthetic End-Products of Phytoplankton Caused by Sea Ice Conditions in the Northern Chukchi Sea.

The recent dramatic decline in sea ice conditions in the Arctic Ocean has led to the ecophysiological changes in the phytoplankton community. Little is currently known about how the physiological status of phytoplankton has changed under rapidly changing environmental conditions in the Arctic Ocean. Using the 13C isotope tracer technique, the carbon allocation of phytoplankton into different photosynthetic end-products was determined in the northern Chukchi Sea on the basis of two Arctic expeditions conducted in 2011 and 2012 to identify the physiological status of phytoplankton. Lipids were the predominant photosynthetic biochemical fraction (42.5%) in 2011, whereas carbon allocation to proteins was most dominant under ice-free conditions in 2012 (47.7%). Based on a comparison of the photosynthetic carbon allocation of phytoplankton according to sea ice conditions, we found that photosynthetic carbon allocation to different macromolecular pools was significantly different depending on the sea ice conditions and that the light conditions caused by different sea ice conditions could be an important reason for the differences in carbon allocation to photosynthetic end-products. Different dominant phytoplankton groups related to size classes also could cause changes in the photosynthetic carbon allocation of phytoplankton related mainly to the lipid synthesis. Our results showed that the physiological status of Arctic phytoplankton could be changed by producing different photosynthetic end-products under current environmental changes. This change in photosynthetic end-products of phytoplankton as a basic food source could be further linked to higher trophic levels in regards to their nutritional and energetic aspects, which could have potential consequences for Arctic marine ecosystems.

Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study.

PURPOSE: This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for advanced soft tissue sarcoma, which has limited treatment options owing to its rare occurrence. MATERIALS AND METHODS: A total of 228 patients received GD therapy for advanced soft tissue sarcoma from 2009 to 2014 in Korea. We retrospectively reviewed the clinical medical records and claims data of these patients. RESULTS: A total of 218 patients in 20 medical centers were included in the final analysis (median age, 50.0 years). The objective response rate was 15.1% (34/218, in the leiomyosarcoma subgroup; 26.3%). The median overall survival and progression-free survival were 10.3 months (95% confidence interval [CI], 8.4 to 12.2) and 3.3 months (95% CI, 2.8 to 4.7), respectively. The treatment was discontinued in 7.8% of patients owing to adverse events; however, there was no adverse event-related death. Neutropenia (35.7%) and anemia (15.1%) were the most frequent grade 3/4 toxicities. Univariate analysis for identifying the predictors of the progression-free survival period revealed that patients aged ≤ 50 years had a hazard ratio of 1.388 (95% CI, 1.027 to 1.875; p < 0.05) relative to those aged > 50 years, and the group with leiomyosarcoma had a hazard ratio of 0.693 (95% CI, 0.493 to 0.975; p < 0.05) relative to the group with other histopathological subtypes. CONCLUSION: GD therapy was tolerable and effective for Korean patients with soft tissue sarcoma. In conclusion, for patients with advanced soft tissue sarcoma, especially leiomyosarcoma, GD therapy could be an important therapeutic option.

Both ERK and Wnt/beta-catenin pathways are involved in Wnt3a-induced proliferation.

The Wnt family of proteins regulates development and cell growth. We identified Wnt3a-based regulatory mechanisms for cell proliferation in NIH3T3 fibroblast cells. The degree of Wnt3a-induced proliferation was reduced by beta-catenin small interfering RNA (siRNA) and extracellular signal-regulated kinase (ERK) siRNA, indicating that both the ERK and Wnt/beta-catenin pathways are involved in Wnt3a-induced proliferation. Wnt3a immediately and transiently activated the Raf-1-MEK-ERK cascade in a manner distinct from that of the beta-catenin increase seen in cells treated with Wnt3a. Wnt3a-induced ERK activation was maintained even though basal ERK activities were reduced by beta-catenin siRNA, indicating that Wnt3a may activate the ERK pathway independently of beta-catenin. The ERK pathway was however, activated by beta-catenin transfection, which was abolished by co-transfection with dominant-negative Tcf-4. Therefore, ERK pathway activation by Wnt signaling could occur at multiple levels, including beta-catenin-independent direct signaling resulting from a Wnt3a and beta-catenin/Tcf-4-dependent post gene transcriptional event. Wnt3a stimulated the G1 to S phase cell cycle progression. This stimulation was reduced by the ERK pathway inhibitor, indicating that Wnt3a promotes proliferation by stimulating the ERK pathway. Wnt3a therefore stimulates the proliferation of fibroblast cells, at least in part, via activation of the ERK and Wnt/beta-catenin pathways.

Extracellular zinc stimulates ERK-dependent activation of p21(Cip/WAF1) and inhibits proliferation of colorectal cancer cells.

Zinc is an important trace element in the body and is involved in both the proliferation and growth arrest of many kinds of cells including colorectal epithelial cells. The aim of this study was to identify the molecular mechanism of the growth regulation of colorectal cancer cells by extracellular zinc. Zinc-stimulated activation of the mitogen-activated protein kinase (MAPK) cascade was measured by immunoblotting and Elk-1 dependent trans-reporter gene expression, and zinc-stimulated p21(Cip/WAF1) activation by immunoblotting, Northern blot analysis and immunochemistry. Cell proliferation was measured by thymidine and bromodeoxyuridine (BrdU) incorporation. By treating colorectal cancer cells with 100 microM ZnCl2, MAPKs were activated in two different phases, the initial weak activation occurred within 5 min and this was followed by a stronger and more prolonged activation. Zinc concomitantly activated Raf-1-MEK-MAPK kinases, and induced Elk-1 dependent trans-reporter gene expression. Prolonged activation of MAPKs by 100 microM of ZnCl2 resulted in the induction and nuclear localization of p21(Cip/WAF1) and was related to the inhibition of both thymidine and BrdU incorporations. These results not only suggest the presence of a mechanism for p21(Cip/WAF1) dependent negative regulation of colorectal cancer cell growth by zinc but also suggest potential usage of zinc to control the growth of colorectal cancer cells.