RESUMEN
Background@#Recent studies suggest that MEK1/2 inhibitors, including binimetinib, significantly improve malignant melanoma (MM) patient survival. Growing evidence suggests that phytochemicals, especially curcumin, can overcome drug resistance in cancer cells through a variety of mechanisms. @*Objective@#This study aims to examine curcumin’s efficacy in vitro combined with binimetinib in human MM cells. @*Methods@#We used 2D monolayer and 3D spheroid human epidermal melanocyte culture models, HEMn-MP (human epidermal melanocytes, neonatal, moderately pigmented), and two human MM cell lines, G361 and SK-MEL-2, to evaluate cell viability, proliferation, migration, death, and reactive oxygen species (ROS) production following single therapy treatment, with either curcumin or binimetinib, or a combination of both. @*Results@#Compared to MM cells treated with single therapy, those with combination therapy showed significantly decreased cell viability and increased ROS production. We observed apoptosis following both single and combination therapies. However only those who had had combination therapy had necroptosis. @*Conclusion@#Collectively, our data demonstrates that curcumin exerts significant synergistic anticancer effects on MM cells by inducing ROS and necroptosis when combined with binimetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.
RESUMEN
Background@#Melanoma is one of the most aggressive and metastatic skin cancers. Although overexpression of Dock180 and Elmo1 has been identified in various cancers, including glioma, ovarian cancer, and breast cancer, their expression and functions in melanoma remain unknown. @*Objective@#This study aims to confirm the expression of Dock180 and Elmo1, their underlying mechanisms, and roles in melanoma. @*Methods@#Both immunohistochemical staining and Western blotting were used to confirm expression of Dock180 and Elmo1 in human melanoma. To identify roles of Dock180 and Elmo1 in cell survival, apoptosis and migration, downregulation of Dock180 or Elmo1 in melanoma cells with small interfering RNA (siRNA) was performed. @*Results@#We identified overexpression of Dock180 and Elmo1 in human melanoma compared to normal skin ex vivo. Inhibition of Dock180 or Elmo1 following siRNA in melanoma cells reduced cell viability and increased apoptosis as supported by increased proportion of cells with Annexin V-PE (+) staining and sub-G0/G1 peak in cell cycle analysis. Moreover, inhibition of Dock180 or Elmo1 regulated apoptosis-related proteins, showing downregulation of Bcl-2, caspase-3, and PARP and upregulation of Bax, PUMA, cleaved caspase-3, and cleaved PARP. Furthermore, knockdown of Dock180 and Elmo1 in melanoma cells reduced cell migration and changed cellular signaling pathways including ERK and AKT. Vemurafenib decreased cell viability in concentration-dependent manner, while transfection with Dock180- or Elmo1-specific siRNA in melanoma cells significantly reduced cell viability. @*Conclusion@#Our results suggest that both Dock180 and Elmo1 may be associated with cancer progression, and can be potential targets for treatment of melanoma.
RESUMEN
Background@#Pityriasis rosea is a self-limiting, acute, or subacute inflammatory skin disease that usually starts with a herald patch on the trunk and progresses to a generalized rash over the trunk and limbs. Some clinical trials have suggested that antibiotic macrolides help shorten the duration of skin manifestations in pityriasis rosea; however, the extent of the benefits is unclear. @*Objective@#To evaluate the effectiveness of antibiotic macrolides compared to placebo in pityriasis rosea. @*Methods@#A computerized search was performed using different databases, including Cochrane, Embase, and PubMed. Five randomized controlled trials were included. Then, statistical analyses of the outcome data extracted from the studies were performed using Rex Software (version 3.0.1). @*Results@#Total 160 records were identified by searching databases including Cochrane, Embase, and PubMed. The results of the meta-analysis demonstrated statistical differences between the use of antibiotic macrolides and placebo in the complete and partial resolution of pityriasis rosea (effectiveness) (RR: 1.84, 95% CI: 1.21∼2.78, p=0.004).However, in subgroup analyses, there were no statistical differences compared to placebo in the skin manifestation effectiveness group for azithromycin and clarithromycin, whereas erythromycin showed statistical differences. @*Conclusion@#Erythromycin was superior to placebo in the treatment of pityriasis rosea. However, this study had some limitations, including insufficient articles and data. Therefore, further investigation is required.
RESUMEN
Background@#Pityriasis rosea is a self-limiting, acute, or subacute inflammatory skin disease that usually starts with a herald patch on the trunk and progresses to a generalized rash over the trunk and limbs. Some clinical trials have suggested that antibiotic macrolides help shorten the duration of skin manifestations in pityriasis rosea; however, the extent of the benefits is unclear. @*Objective@#To evaluate the effectiveness of antibiotic macrolides compared to placebo in pityriasis rosea. @*Methods@#A computerized search was performed using different databases, including Cochrane, Embase, and PubMed. Five randomized controlled trials were included. Then, statistical analyses of the outcome data extracted from the studies were performed using Rex Software (version 3.0.1). @*Results@#Total 160 records were identified by searching databases including Cochrane, Embase, and PubMed. The results of the meta-analysis demonstrated statistical differences between the use of antibiotic macrolides and placebo in the complete and partial resolution of pityriasis rosea (effectiveness) (RR: 1.84, 95% CI: 1.21∼2.78, p=0.004).However, in subgroup analyses, there were no statistical differences compared to placebo in the skin manifestation effectiveness group for azithromycin and clarithromycin, whereas erythromycin showed statistical differences. @*Conclusion@#Erythromycin was superior to placebo in the treatment of pityriasis rosea. However, this study had some limitations, including insufficient articles and data. Therefore, further investigation is required.
RESUMEN
The index on myocardial contractility of pure mitral regurgitation(MR) after mitral valve replacement is believed to be useful in determining proper operation time before irreversible myocardial damage by volume overload. Thus the authors examined pre and post-operative echocardiographic results of 20 cases of pure MR patients who had been admitted to Pusan National University hospital and compared the usefulness of each index. Pre and post-operative echocardiographic results were as follows respectively ; 1) Left ventricular internal dimension in diastole(LVIDd) were 6.49+/-0.19cm and 5.51+/-0.17cm. 2) Left ventricular internal dimension in systole(LVIDs) were 4.26+/-0.12 and 3.79+/-0.18cm. 3) Ejection fraction were 71.28+/-1.57% and 59.24+/-3.05%. 4) Fractional shortening(FS) were 34.09+/-1.18% and 27.21+/-1.84%. 5) Mean Vcf were 1.53+/-0.08cm/sec and 1.18+/-0.09cm/sec. 6) Left ventricular end-diastolic volume index(EDVI) were 196.35+/-18.33cc/m2 and 98.46+/-9.96cc/m2. 7) Left ventricular end-systolic volume index(ESVI) were 55.28+/-5.12cc/m2 and 41.88+/-6.07cc/m2. 8) Left ventricular end-systolic wall stress/ESVI(ESS/ESVI) were 2.3+/-0.21 and 3.91+/-0.83. ESS/ESVI showed significantly(p6cm, LVIDs>4cm, and ESS/ESVI<2, the prognosis was poor due to myocardial damage by mitral regurgitation.