Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by a sensitive photoabsorber following exposure to NIR light. Most studies of NIR-PIT have been performed in xenograft models of cancer. The purpose of this study was to evaluate the therapeutic effects of NIR-PIT in a transgenic model of spontaneous lung cancer expressing human EGFR (hEGFR-TL). Mice were separated into 3 groups for the following treatments: (1) no treatment (control); (2) 150 μg of photoabsorber, IR700, conjugated to panitumumab, an antibody targeting EGFR [antibody-photoabsorber conjugate (APC)] intravenously (i.v.) only; (3) 150 μg of APC i.v. with NIR light administration. Each treatment was performed every week up to three weeks. MRI was performed 1 day before and 3, 6, 13, 20, 27, and 34 days after first NIR-PIT. The relative volume of lung tumors was calculated from the tumor volume at each MRI time point divided by the initial volume. Steel test for multiple comparisons was used to compare the tumor volume ratio with that of control. Tumor volume ratio was inhibited significantly in the NIR-PIT group compared with control group (P < 0.01 at all time points). In conclusion, NIR-PIT effectively treated a spontaneous lung cancer in a hEGFR-TL transgenic mouse model. MRI successfully monitored the therapeutic effects of NIR-PIT. Mol Cancer Ther; 16(2); 408-14. ©2016 AACR.

The advent of multi-omic profiling of tumors, together with the increasing affordability of high-throughput drug screening programs, has helped usher in a new era of molecular targeted therapies for many solid malignancies. However, there has been limited success in esophageal adenocarcinoma. Until recently, preclinical drug development for this cancer has been largely limited to a small number of cell line models. Now, the increasing availability of patient-derived xenografts and novel metastatic models are helping to bridge the gap between scientific discovery and patient care. These platforms are valuable adjuncts for drug testing. Nevertheless, further work is required to develop systems that model the tumor microenvironment, including cancer cell interactions with the immune system, which will be particularly relevant for the translation of novel immunotherapies for esophageal adenocarcinoma.

Agronomic and environmental factors affect quality and quantity of constituents in Saffron.  In this study, we compared chemical and antioxidant compounds of organic (OS) and inorganic (IOS) stigma of saffron and evaluated their anti-proliferative and apoptosis effects on cancer cells. Total antioxidant capacity of both saffron were characterized by FRAP, DPPH and Folin-Ciocalteu. HPLC and MTT methods were used to assay the amount of their secondary metabolites and anticancer effects, respectively. The expression of two apoptosis-related genes in treated cells evaluated by quantitative Real Time-PCR analysis. Our data indicated that OS has more secondary metabolites, antioxidant and cytotoxic properties compared to IOS. OS significantly inhibited cell viability in a dose- and time- dependent manner. Herb-induced apoptosis associated with increased expression of Bax and decreased Bcl2 gene leading eventually to a time-dependent increase in Bax/Bcl-2 ratio. Therefore, we can suggest organic saffron has promising and selective inhibitory effects on cancer cell proliferation.

The objective of this study was to determine the incidence of arrhythmias and device (internal cardiac defibrillator/cardiac resynchronization therapy defibrillator) therapies in patients with a diagnosis of cardiomyopathy and anthracycline exposure.

LLL-3, an anthracene derived compound, has been shown to be a promising therapeutic agent for the treatment of some kinds of cancer such as chronic myeloid leukemia and glioblastoma. However, no data regarding the toxic properties of this compound have yet been described in the literature. The present work aimed to investigate the mutagenic and genotoxic activities of LLL-3 using the TA97, TA98, TA100, TA102 and TA104 Salmonella/microsome strains for the Ames test and the micronucleus assay with the mouse macrophage cell line RAW 264.7. The findings showed that LLL-3, at doses of 0.001, 0.01, 0.1, 1.0 and 10.0 μg/plate, did not induce mutagenic activity in the Salmonella strains used under the conditions tested, and nor did it present genotoxicity in RAW 264.7 cells, at 10.0, 100.0 and 1000.0 μg/mL doses. Moreover, it is important to point out that the mitotic index of the cells decreased after exposure to LLL-3 under the same conditions tested, which may suggest some cytostatic effect, since this compound acts by inhibiting STAT3. Since most drugs used in the treatment of cancer present mutagenic activity as an adverse effect, these results suggest that LLL-3 is a promising drug for cancer therapy.

Cytochrome P450 1B1 (CYP1B1) is an anticancer therapeutic target due to its overexpression in a number of steroid hormone-related cancers. One anticancer drug discovery strategy is to develop prodrugs specifically activated by CYP1B1 in malignant tissues to cytotoxic metabolites. Here, we aimed to develop an in vitro screening model for CYP1B1-targeted anticancer prodrugs using the KLE human endometrial carcinoma cell line. KLE cells demonstrated superior stability of CYP1B1 expression relative to transiently transfected cells and did not express any appreciable amount of cognate CYP1A1 or CYP1A2, which would have compromised the specificity of the screening assay. The effect of two CYP1B1-targeted probe prodrugs on KLE cells was evaluated in the absence and presence of a CYP1B1 inhibitor to chemically "knock out" CYP1B1 activity (CYP1B1 inhibited). Both probe prodrugs were more toxic to KLE cells than to CYP1B1-inhibited KLE cells and significantly induced G0/G1 arrest and decreased the S phase in KLE cells. They also exhibited pro-apoptotic effects in KLE cells, which were attenuated in CYP1B1-inhibited KLE cells. In summary, a KLE cell-based model has been characterized to be suitable for identifying CYP1B1-targeted anticancer prodrugs and should be further developed and employed for screening chemical libraries.

Eye disorders are one of the characteristic adverse events associated with S-1 chemotherapy. In this retrospective study, we investigated the frequency and outcome of eye disorders associated with S-1 chemotherapy in gastric cancer patients. This retrospective study included 75 advanced gastric cancer patients who received S-1 monotherapy between January 2014 and December 2015. We retrospectively evaluated the frequency, Grade, and treatment of eye disorders. Eye disorders were observed in 16 patients(21%). The median time of onset was 3(range, 1-8)months. Grade 2 watering eyes, eye discharge, and conjunctivitis were reported in 14, 8, and 4 patients, respectively. Artificial tears, fluorometholone eye-drops, and both of these treatments were used in 7, 1, and 8 patients, respectively. Ophthalmologic examination was performed for 3 patients. No delay or reduction of S-1 therapy was required for the eye disorders. Eye disorders associated with S-1 therapy in gastric cancer patients did not affect treatment if managed properly using eye drops.

A 74-year-old man was diagnosed with hepatocellular carcinoma(HCC; S4/8)and underwent anterior segment resection of the liver in 2015. He was hospitalized with a wound infection 2 months after surgery. On the 8th hospital day he complained of respiratory discomfort. A CT showed multiple lung metastases and a ground-glass appearance in both lungs. We diagnosed interstitial pneumonia with metastatic lung tumors. Steroid therapy was performed for the interstitial pneumo- nia(prednisolone 1,000mg/day×3 days), and sorafenib therapy was initiated for the metastatic lung cancer(starting from 200mg/day to 800mg/day). The prednisolone improved his symptoms. The lung metastatic tumors shrunk by the 36th hospital day after the CT. However, he developed difficulty in breathing again on the 58th hospital day, and again showed a ground-glass appearance in both lungs by CT. We thought it was drug-induced interstitial pneumonia and we discontinued oral sorafenib. He underwent steroid pulse therapy, but his symptoms did not improve and he died.

We report a 43-year-old TSC man with repeated hemorrhage of bilateral renal AML. He was diagnosed with TSC based on the findings of facial angiofibroma, mental retardation and epilepsy in childhood. In 2011, he experienced three times in AML-associated hemorrhage from the left kidney and received selective transarterial embolotherapy (TAE). In 2013, he also experienced AML-associated hemorrhage from the right kidney and received selective TAE. To control his AML, treatments with Everolimus was started and well tolerated. So far, his renal AML remarkably shrunk without retroperitoneal hemorrhage for 24 months, while he had some episode of side effect.

Since late 90s of last century the new age of directed therapy began using mainly biological constructs produced in rodents called monoclonal antibodies. The side effects of monoclonal antibodies were a challenge for pharmaceutical companies to improve the biological properties of these biological drugs. The humanization of monoclonal constructs was an idea to improve monoclonal antibodies next generation activity cancer cell reduction in humans. Moreover for some other patients sensitive for monoclonal antibodies therapy could also potentially induce immunological differences that might imply on human health. The new idea related to monoclonal antibodies was to design a small molecule constructs of nanoantibodies with ability to enter into cells. Such small molecules could find their targets inside human cells, even in nuclei leading to differences in cancer cells expression. The existing knowledge on monoclonal antibodies as well as directed activity of nanoantibodies could improve anticancer treatment efficancy of diseases.

Administration of plant extracts for the treatment of several different diseases is an important approach ofmodern medicine.The reason must be an easy way of application, low price and the complex action of herbal medicines. The aim of the work was to study the effect of extract of walnut (Juglans regia L.) septa on the functional characteristics of erythrocytes during administration of cytotoxic agent - cyclophosphamide (experimental model of leukopenia). The material for the study was blood of the intact and experimental white mice. Sorption capacity and resistance to lysis of erythrocyte membrane have been determined by the spectrophotometric methods. According to the gained results, administration of cyclophosphamide had an influence on sorption capacity of erythrocytes and the given characteristic was increased only on the 8th day of cyclophosphamide administration, compared to control. Sorption capacity of erythrocytes was increased more on 8th day after combined application of cyclophosphamide and exctract of walnut septa. Resistance of erythrocytes to lysis was also increased after administration of the cyclophosphamide and this characteristic was further increased in case of combined application of cyclophosphamide and exctract of walnut septa. Thus, the stimulative effects of extract of walnut septa have been established on sorption capacity and resistance to lysis of erythrocytes in case of nonspecific damage of the cells.

Chemotherapy-induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti-cancer drugs are: platinum-based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids.

Rhamnetin is a flavonoid that has antioxidant, anti-inflammatory and anti-cancer effects. Nucleolar-organizing regions are the ribosomal genes region. We aimed to identify whether rhamnetin has an effect on cell proliferation and whether AgNOR proteins may be used for the detection of therapeutic benefits of the drugs and new metabolites, which have the potential of being used for cancer treatments.

Certain cancer therapies, including radiation therapy and some types of chemotherapies, are associated with increased risk of cardiovascular disease (CVD) and events. Some of these effects such as those presented by anthracyclines, radiation therapy, cisplatin, as well as those presented by hormone therapy for breast cancer-usually taken for many years for some breast and prostate cancers-are long-lasting and associated with cardiovascular events risk more than 20 years after cancer treatment. Cardiovascular testing, diagnostic assessment of suspected cardiovascular symptomatology, as well as laboratory tests for CVD risk factors are imperative. The early recognition and treatment of CVD processes that arise in survivorship years is pivotal, with specific attention to some CVD processes with specific suggested treatment modalities. Preventive measures include adequate screening, the use of medications such as ACE inhibitors/angiotensin receptor blockers and/or beta blockers, statin therapy and aspirin in persons who warrant these medications, as well as therapeutic lifestyle modifications such as exercise/physical activity, weight loss and appropriate diet for a healthy lifestyle. Periodic follow-up with a good primary care physician who understands the risks associated with cancer therapy is important, and referral to onco-cardiology for further management of cardiovascular risk in these survivors is based on a patient's cardiovascular risk level and the type, amount and duration of cancer therapies received during the patient's lifetime.

This retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy.

Adjuvant treatment with aromatase inhibitors improves outcomes in postmenopausal women with hormone-sensitive early breast cancer; however, they should not be used in premenopausal women. Menopausal status is the most important factor in the choice of the hormonal treatment. There is no direct correlation between amenorrhea and ovarian function, as even the patients with amenorrhea may present with premenopausal plasma estradiol levels. The evaluation of hormonal status becomes more complicated in patients taking tamoxifen, which might lead to further increase of plasma estradiol levels. Therefore, its evaluation before and during the treatment with aromatase inhibitors is clinically important. There is a considerable caution needed when indicating aromatase inhibitors in patients with menopause caused by previous adjuvant chemotherapy, while recovery of ovarian function may appear after a certain period. This could take from 4 to 59 months (12 months on average) and it might not be accompanied by menses. This happens typically in women younger than 40 years, who should, therefore, not be treated by aromatase inhibitors alone. This supports the notion that monitoring of plasma estradiol levels is crucial in women from 40 to 50 years of age, especially before the start of aromatase inhibitors treatment.Key words: breast cancer - premenopause - postmenopause - perimenopause - estradiol - aromatase inhibitorsThis work was supported by MEYS - NPS I - LO1413 for RECAMO.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 18. 2. 2016Accepted: 29. 6. 2016.

Pulmonary arterial smooth muscle cells (PASMCs) in the medial layer of the vessel wall are involved in vessel homeostasis, but also for pathologic vascular remodeling in diverse diseases, such as pulmonary arterial hypertension (PAH). Pulmonary vascular remodeling in PAH results in vascular disorders, but its underlying molecular mechanisms are still not to be fully disclosed. In this study, we investigated the expression and function of the transforming growth factor (TGF)-β1 in human PASMC cultured under the condition of hypoxia and elucidated the effect of schisandra chinensis and its active ingredients on proliferation, migration, and apoptosis in human PASMCs. We demonstrated that schisandrin B (Sch.B) alleviated the severity of PAH in PASMCs cultured under the condition of hypoxia. Significant upregulation of TGF-β1 was observed in hypoxia-induced human PASMCs. Interestingly, administration of Sch.B substantially attenuated TGF-β1 level in these PASMCs. In order to elucidate Sch.B function, the hypoxia-induced human PASMC was stimulated with Sch.B or cotreatment with TGF-β1 in vitro. In agreement with its TGF-β1-reducing effect, Sch B relieved human PASMCs migration and promoted the apoptosis of human PASMCs, by activation of TGF-β1 downstream signal pathways in PASMCs. In contrast, co-treatment with TGF-β1 promoted human PASMC proliferation and migration and inhibited the apoptosis of human PASMC, which can attenuate the protective role of Sch.B in human PASMC. Taken collectively, these findings suggest that the vascular relaxation evoked by Sch.B was mediated by direct effect on vascular smooth muscle cell via TGF-β1 downstream signal pathways.

The magnitude of expression of cathepsin L, often upregulated in the tumor microenvironment, correlates with the invasive and metastatic nature of certain tumors. Inhibition of cathepsin L represents an emerging strategy for the treatment of metastatic cancer. A potent, small-molecule inhibitor (referred to as KGP94) of cathepsin L, and new KGP94 analogues were synthesized. (3,5-Dibromophenyl)-(3-hydroxyphenyl) ketone thiosemicarbazone (22), with an IC50 value of 202nM, exhibited similar inhibitory activity against cathepsin L compared to KGP94 (IC50=189nM). Due to limited aqueous solubility of KGP94, a water-soluble phosphate salt (KGP420) was prepared in order to facilitate future in vivo studies. Enzymatic hydrolysis with alkaline phosphatase (ALP) demonstrated that the phosphate prodrug, KGP420, was readily converted to the parent compound, KGP94.

Neovascularization (NV) of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG), presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine-glycine-aspartic acid (RGD) peptide-hyaluronic acid (HA)-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs) was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs) in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV), with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a spherical shape and shell structure of about 200 nm. A slow-release pattern was observed in the nanoformulation at about 30% after 30 hours. Surface plasmon resonance confirmed that GEH-RGD NPs specifically bound to the integrin αvβ3. In vitro cell-viability assay showed that GEH-RGD efficiently inhibited HUVEC proliferation at low EGCG concentrations (20 μg/mL) when compared with EGCG or non-RGD-modified NPs. Furthermore, GEH-RGD NPs significantly inhibited HUVEC migration down to 58%, lasting for 24 hours. In the corneal NV mouse model, fewer and thinner vessels were observed in the alkali-burned cornea after treatment with GEH-RGD NP eyedrops. Overall, this study indicates that GEH-RGD NPs were successfully developed and synthesized as an inhibitor of vascular endothelial cells with specific targeting capacity. Moreover, they can be used in eyedrops to inhibit angiogenesis in corneal NV mice.

Pectic Polysaccharide (PP) from dietary sources has been known to prevent cancer growth and hence impede cancer progression. We evaluated anticancer effect of Pectic-Oligosaccharide isolated from Sour Raw Tomato (SrTPO); its bioavailability and structure elucidated from purified fraction (SrTPO1). SrTPO1 inhibited galectin-3 activity with MIC of 0.25 ug/mL (100 fold better than standard galactose), inhibited the growth of AGS cells (IC50 3.4μg/mL) and induced apoptosis (70% inhibition at 30μg/mL concentration). Normal- NIH 3T3 cells were not affected by SrTPO as opposed to doxorubicin, a known anticancer drug, which reduced 76% viability at equivalent dose. SrTPO1 was identified as RhamnogalacturonanI-arabinogalactan (RGI-AG), where repeated alternative rhamnose and galacturonic acid residues were observed while arabinose in the branch point and β-1,4 linked galactose in the linear chain form. SrTPO was found to be bioavailable as evaluated by FITC labelled oligos inside the cell, which was in reciprocal proportion with apoptosis.