This research study explored the anti-cancer effects of natural materials in South Korea. Although South Korea has a long history of traditional medicine, many natural materials of South Korea have not yet been introduced to the rest of the world because of language barriers and inconsistent study conditions. In the past 3 years, 56 papers introducing 56 natural materials, which have anti-cancer effects, have been published by scientists in South Korea. Further, these studies have introduced five kinds of natural materials presented in research papers that were written in Korean and are therefore virtually unknown overseas. The anti-cancer effects were confirmed by 2-3 cancer markers in the majority of the studies, with the most common targets being breast cancer cells and gastric cancer cells. These cancers have the greatest incidence in South Korea. The natural materials studied not only exhibit anti-cancer activity but also display anti-inflammatory, anti-oxidative stress, and anti-diabetic activities. They have not yet been used for the direct treatment of disease but have potential as medicinal materials for alternative and complementary medicine for the treatment of many modern diseases. Many natural materials of South Korea are already known all over the world, and with this study, we hope to further future research to learn more about these natural medicines.

Vaginal intraepithelial neoplasia (VAIN) represents a variety of changes that initiate as an intraepithelial squamous lesion with the possibility of resulting in cancer.

An ever-increasing proportion of young males treated for cancer are cured. Therefore, one of the major challenges of modern Clinical Oncology is to ensure good quality of life. Cancer disease per se as well as cancer treatment may have a negative impact on androgen production, thereby leading to subclinical or clinically overt hypogonadism. Since the symptoms of androgen deficiency are rather unspecific, it is important that reproductive hormone levels be checked in young men who have been treated for cancer. As androgen deficiency in men is associated with increased long-term risk of osteoporosis as well as cardiovascular and metabolic disease, those cancer survivors who present with signs of insufficient androgen production should be followed and preventive as well as therapeutic measures, including androgen replacement therapy, should be applied according to the current guidelines.

Lysosome membrane permeabilization (LMP) mediates cell death in a variety of cancer cells. However, little is known about lysosomes and LMP in chronic lymphocytic leukemia (CLL). Owing to drug resistance and toxicity in CLL patients, better treatment strategies are required. Our results show that CLL cells were sensitive to the lysosomotropic agent siramesine. Furthermore, this drug was more effective in CLL cells, regardless of prognostic factors, compared with normal B cells. Siramesine caused LMP, lipid peroxidation and transcription factor EB nuclear translocation followed by mitochondrial membrane potential loss and reactive oxygen species release. Siramesine-induced cell death was blocked by lipid antioxidants, but not by soluble antioxidants or protease inhibitors. To determine whether CLL cells had altered lysosomes, we investigated sphingolipid metabolism as the lysosome is a hub for lipid metabolism. We found that CLL cells had more lysosomes, increased sphingosine-1-phosphate phosphatase 1 (SPP1) expression, and increased levels of sphingosine compared with normal B cells. Raising sphingosine levels increased LMP and cell death in CLL cells, but not in normal B cells. Together, these results show that excess sphingosine in CLL cells could contribute to their sensitivity toward LMP. Thus, targeting the lysosome could be a novel therapeutic strategy in CLL.

Hypothermia of the scalp tissue during chemotherapy treatment (scalp cooling) has been shown to reduce or prevent chemotherapy-induced hair loss. In this study, numerical models are developed to investigate the interaction between different types of external scalp cooling devices and the human scalp tissue. This work focuses on improving methods of modeling scalp cooling devices as it relates specifically to the prevention of chemotherapy-induced alopecia. First, the cooling power needed for any type of device to achieve therapeutic levels of scalp hypothermia is investigated. Subsequently, two types of scalp cooling devices are simulated: a pre-cooled/frozen cap design and a liquid-cooled cap design. For an average patient, simulations show that 38.5W of heat must be extracted from the scalp tissue for this therapy in order to cool the hair follicle to 22°C. In practice, the cooling power must be greater than this amount to account for thermal losses of the device. Simulations show that pre-cooled and liquid-cooled cap designs result in different tissue temperatures over the course of the procedure. However, it is the temperature of the coolant that largely determines the resulting tissue temperature. Simulations confirm that the thermal resistance of the hair/air layer has a large impact on the resulting tissue temperatures. The results should be correlated with experimental data as an effort to determine the optimal parameter choices for this model.

High-dose etoposide is used in conditioning regimens for allogeneic stem cell transplantation. The limited stability of the drug induces barriers for its use for pharmacists, nurses and patients. When using a concentration of 10 mg/mL etoposide in physiologic saline, limitations can be overcome. This study provides stability data for etoposide in a high concentration that can be used in conditioning regimens. The solution was stable for 48h at 5°C, for 48h at 5°C followed by 8h at 25°C and for 24 h at 25°C.

Platinum derivatives play a very important role in cancer therapy. Despite their outstanding results in the treatment of tumors with different locations, the occurrence of hypersensitivity reactions raises issues when it comes to therapy decision, because the changing of chemotherapy line could influence the tumor's evolution. Over the years the scientific community has paid particular attention to the mechanism by which this occurs and to identification of predictive factors. The purpose of this case-control, retrospective study was to find new predictive markers for the occurrence of allergic reactions to platinum derivatives.

To evaluate the cytotoxic and apoptotic effects of bishydroxycoumarin (BHC) against human glioma cells and to study their mode of action.

Impressed by the exceptional anticancer activity of cinnamon, the present study was conducted to elucidate the anticancer potential of essential oil of Cinnamon (EOC).

Cervical carcinoma is the second most common malignancy in females and most of the cases are found in developing countries. The objectives of the present study were (a): to demonstrate the antiproliferative and apoptotic effects of Achillea falcata (A.falcata) extract in human cervical cancer cells (HeLa), and (b): to study the effect of the extract on cellular morphology, cell cycle phase distribution and mitochondrial membrane potential.

Podophyllotoxin (PT) and its clinically used analogues are known to be powerful antitumour agents. These compounds contain a trans fused strained γ-lactone system, a feature that correlates to the process of epimerisation, whereby the trans γ-lactone system of ring D opens and converts to the more thermodynamically stable cis epimer. Since these cis epimers are known to be either less active or lacking antitumour activity, epimerisation is an undesirable feature from a chemotherapeutic point of view. To circumvent this problem, considerable efforts have been reported, amongst which is the synthesis of azapodophyllotoxins where the stereocentres at C2 and C3 are removed in order to preclude epimerisation. Herein we report the identification of a novel C3 hydroxy, cis-selective γ-lactone configuration of ring C in the azapodophyllotoxin scaffold, through an efficient stereoselective multicomponent reaction (MCR) involving fluorinated and non-fluorinated aldehydes. This configuration releases the highly strained trans γ-lactone system in podophyllotoxin analogues into the more thermodynamically stable cis γ-lactone motif and yet retains significantly potent activity. These compounds were evaluated against the human cancer lines MCF-7 and 22Rv1 in vitro. Fourteen out of the seventeen tested compounds exhibited sub-micromolar activity with IC50 values in the range of 0.11-0.91 μM, which is comparable and in some cases better than the activity profile of etoposide in this assay. Interestingly, we obtained strong evidence from spectroscopic and X-ray data analyses that the previously reported structure of similar analogues is not accurate. Molecular modelling performed using the podophyllotoxin binding site on β tubulin revealed a novel binding mode of these analogues. Furthermore, sub-cellular study of our compounds using immunolabelling and confocal microscopy analyses showed strong microtubule disruptive activity, particularly in dividing cells.

In a previous study, ethyl acetate extract of Coprinus comatus was found to reduce viability of human ovarian cancer cells. The objective of the current research was to clarify the mechanism of action of this extract. Ovarian cancer cells (ES-2) were subjected to ethyl acetate extract of C. comatus for different concentrations or exposure times. Cell cycle analysis and annexin V staining were performed using an automated flow cytometer. DNA fragmentation was detected using the TUNEL assay. Western blot analysis was performed for the assessment of activation of caspases -3, -8, and -9. Results revealed that treatment of ES-2 cells with ethyl acetate extract of C. comatus (100 μg/ml medium), for 48 h or for 72 h resulted in an increased number of cells at the sub-G1 phase of the cell cycle. These treatments also resulted in an increased number of apoptotic cells (positively stained by annexin and positively labeled by TUNEL), in comparison to the control. Reduced levels of procaspases -3, -8, and-9 were also detected in treated cells. In conclusion, ethyl acetate extract of C. comatus induces apoptosis in ovarian cancer cells (ES-2), via both extrinsic and intrinsic pathways. Meanwhile, more investigations are needed to demonstrate weather the apoptotic effect on ovarian cancer cells is accomplished by one active compound, or combined activities of different compounds that exist in the extract.

The birch polypore Piptoporus betulinus was among two mushrooms that were found in the Iceman's bag. Recent studies indicated that P. betulinus was probably used as a religious and medicinal item. In order to examine the medicinal potential of P. betulinus, hot water (HW), partially purified (PP), and alkali extract (HA) were prepared and tested for antioxidant, antimicrobial, cytotoxic, and angiotensin I-converting enzyme (ACE) inhibitory activity. All tested samples exhibited moderate cytotoxic activity, and HW appeared as the most effective (IC50 = 0.8 ± 0.1 mg/ml for HeLa cells). HA proved to be a good 1,1-diphenyl-2-picrylhydrazyl radical scavenger and exhibited the strongest ferric-reducing power (EC50 = 0.07 ± 0.3 mg/ml). The same extract (HA) also expressed the strongest ferric-reducing power (EC50 = 0.99 ± 0.1 mg/ml). Hot alkali extraction contributed significantly to ACE inhibitory activity (EC50 = 0.06 ± 0.00 mg/ml) and to antimicrobial activity, especially against highly resistant Enterococcus faecalis (minimum inhibitory concentration: 0.156 ± 0.000 mg/ml; and minimum bactericidal concentration: 1.25 ± 0.00 mg/ml).

Diabetic retinopathy is a common complication of uncontrolled diabetes. A complication is diabetic macular edema, which is the leading cause of blindness in patients with diabetic retinopathy. Historically, management of these conditions was laser photocoagulation with regulation of blood pressure, blood sugar, and cholesterol. The initial studies demonstrated that this treatment regimen prevented further visual deterioration but did not improve visual acuity. Novel studies identifying the presence of vascular endothelial growth factor (VEGF) in the eye with accompanying elucidation of diabetic pathophysiology allowed for the development of alternative therapies, namely antibodies against VEGF and corticosteroids. These two therapies revolutionized the management of diabetic macular edema by not only preventing vision loss, but also improving overall vision. In this review, we outline the major breakthroughs and underlying thought processes of the paradigm shifts that have occurred in management of these conditions. Further, we present how the evolving role of anti-inflammatory and anti-VEGF therapies, in a combinatorial approach, may provide further permutations to optimize treatment.

Nephrotoxicity is the major dose-limiting toxicity of cisplatin (CDDP). The aim of this study was to develop a pharmacokinetic (PK)/toxicodynamic (TD) model of CDDP-induced acute renal injury in rats and to simulate nephrotoxicity at various dosing rates. CDDP was administered to rats by a 30-s bolus or a 2-h infusion (1.0, 2.5, 5.0, and 7.5 mg/kg). Unbound CDDP concentrations in plasma and urine were determined up to 2 h after administration in the PK study, and plasma creatinine (Cr) levels were monitored for up to 7 days as an index of nephrotoxicity in the TD study. The PK was linear and was fitted with a traditional 2-compartment model. The TD was nonlinear and differed between dosing rates. The creatinine concentration profiles were fitted with a signal transduction-indirect response model. Population analysis using a nonlinear mixed-effect model was adapted to the developed PK/TD model and was well-validated. Dosing simulations from the developed population PK/TD model indicated that CDDP-induced nephrotoxicity was due to not only Cmax but also the time above the toxic concentration of CDDP. Prolongation of infusion time will not necessarily attenuate acute nephrotoxicity. This study demonstrated the potential utility of PK/TD modeling for preventing nephrotoxicity.

Efficiency of mono-sialogangliosides to load Paclitaxel (Ptx) has recently been found to depend on the structure of the polysaccharide chain. In this study, we demonstrated that incorporation of only one more sialic acid into the ganglioside molecule, independently of its position, causes a 4-fold increase in Ptx-loading capacity, the maximum being at a 5:1 molar ratio (di-sialoganglioside/Paclitaxel, GD/Ptx). These complexes are stable in solution for at least 3 months, and over 90% of Ptx remains loaded in the micelles after extreme stress conditions such as high-speed centrifugation, lyophilization, or freeze-thaw cycles. Ganglioside micelles protect 50% of the initially loaded Ptx from alkaline hydrolysis after 24 h at pH 10. Dynamic light scattering studies revealed that GD micelles increase their size from 9 to 12 nm when loaded with Ptx. Transmission electron microscopy shows a homogeneous population of spherical micelles either with or without Ptx. In vitro biological activity was similar to that of the free drug. These results provide further options of self-assembled nanostructures of di- and tri-sialogangliosides with a higher loading capacity.

Because of the insolubility of miriplatin in water, miriplatin and lipiodol suspension is the sole formulation of miriplatin approved in Japan to treat hepatocellular carcinoma by transcatheter arterial chemoembolization. Until now, there have been no reports of other pharmaceutical formulations of miriplatin except miriplatin/lipiodol suspension. In this study, we aimed not only to develop miriplatin-loaded liposomes (lipomiriplatins) which could be administrated systematically for tumors besides hepatocellular carcinoma but also to ascertain whether miriplatin, like its analog of NDDP, was a liposome-dependent antitumor agent. We found that miriplatin could be successfully incorporated into liposomes, and both the stability and antitumor activity of lipomiriplatins were independent of the liposomal compositions. Especially, HPLC was successfully established as the quantitative method for lipomiriplatins, which completely eliminated the interference of cholesterol. Lipomiriplatins possessed favorable colloidal properties (99.71 ± 0.56 nm, -50 mV), high drug-loading capacity (about 2.2 mg/mL), excellent entrapment efficiency (>95%), and robust stability. The remarkable antitumor activities of lipomiriplatin were proved to be mediated by inducing cell apoptosis and were comparable to that of the commercial cisplatin and oxaliplatin injections, indicating that lipomiriplatins showed great promise for future potential clinical application via systematic administration.