Combination strategies involving chemotherapy and monoclonal antibodies (mAb) are commonly used in attempts to produce better clinical outcomes. This practice has led to new and ongoing toxicities that may lead to reductions in dose or noncompliance, limiting the effectiveness of treatment. Viscum album L (VA) preparations are widely used in Europe as additive therapy and have been associated with reduced chemotherapy-related adverse reactions and increased health-related quality of life. Concomitant VA therapy might also reduce toxicity related to mAb. This retrospective study investigated the safety of combined treatment with VA and mAb in cancer patients. A total of 43 patients had combined therapy (474 exposures); 12 had VA without mAb (129 exposures), and 8 had mAb without VA (68 exposures). Most patients (89.3%) received concomitant chemotherapy or supportive therapies. A total of 34 patients (60.7%) experienced 142 adverse events (AEs). Leucopenia (14.1% of all events), acneiform rash (8.5%), and stomatitis (6.3%) occurred most frequently. Longitudinal logistic regression analysis suggested a nearly 5 times higher odds of experiencing an AE following treatment with mAb compared with mAb plus VA (95% CI = 1.53-16.14). Our results, together with theoretical consideration of potential botanical-drug interactions, suggest that combined treatment with VA and mAb is safe.

In this study, we developed a novel three-dimensional (3D) cancer cell chip using a three-floor hierarchical 3D pyramid structure (3D pyramid) to simulate 3D tumor cell growth in vitro and to detect anticancer drugs. The proposed 3D pyramidbased cancer cell chip offered substantial advantages for the agglomerate formation of tumor cells, in which cells could be maintained as tumor spheroids for up to 3 weeks. Soon after HeLa tumor cells adhered to the micropatterned pillar sidewalls, they were suspended between the pillars based on scanning electron microscopy images. Treatment with the anticancer drug oleanolic acid resulted in 46.33% and 5.86% apoptotic cells on the 2D plate and 3D pyramid-based cell chip, respectively, compared with only 0.06% apoptotic cells in the control. The increase in chemoresistance to anticancer drugs in the 3D pyramid-based cell chip might be a result of cell confluence and hypoxia due to the spheroid formation of tumor cells in the 3D pyramid structure. These results indicated that the proposed cell chip could potentially be used for anticancer drug screening or can be incorporated into other models aimed at prolonging various cell functions in culture.

Chemotherapy for breast cancer is significantly restricted by the tumor's physio-pathological complexity. Here we have constructed a targeted nano-system based on PEGylated poly (D, L-lactide) (PEG-PDLLA) using a novel ligand, CLKADKAKC (CK3) peptide, for active targeting to Neuropilin-1-rich breast cancer cells. CK3 increased the cellular uptake of micelles 4.7-fold compared with the free drug and nearly 2.2-fold compared with the unmodified micelles (PM), respectively. Furthermore, in vivo imaging revealed that CK3-modified micelles (CK3-PM) had excellent specific tumor cells targeting and the drug accumulation was also enhanced. When paclitaxel (PTX) was loaded into micelles, CK3-PM-PTX induced the strongest inhibition and apoptosis against MDA-MB-231 cells in vitro and in vivo. These results demonstrated that CK3-modified PEG-PDLLA micelles developed in this study could be a potential targeted vehicle for enhancing the chemotherapy of breast cancers.

A disulfide bond containing deoxycholic acid-grafted dextran (Dex-SSDCA) was successfully prepared for drug delivery. The Dex-SSDCA polymers can self-assemble into nanomicelles at concentrations below 56 g/mL and encapsulate doxorubicin (DOX) effectively. When exposed to 10 mM Dithiothreitol (DTT), the nanomicelles disassembled rapidly and released DOX immediately. The DOX-loaded Dex-SSDCA nanomicelles were able to reverse the drug resistance of MCF-7/Adr cells and inhibit their growth in vitro. Moreover, DOX-loaded Dex-SSDCA nanomicelles could significantly suppress the growth of subcutaneous SKOV-3 ovarian cancer in vivo, exerting stronger efficiency on inhibiting tumor angiogenesis and proliferation while aggravating apoptosis of tumor cells, in comparison with the negative control and free DOX. The in vivo toxicity evaluation demonstrated that the Dex-SSDCA micelles reduced DOX-induced side effects. This redoxresponsive amphipathic dextran is able to enhance the antitumor efficiency and reduce the toxicity of doxorubicin, thus has a potential as a drug carrier for cancer therapy.

A meeting of regional experts was convened in Manila, Philippines, to develop a resource-stratified chemotherapy-induced nausea and vomiting (CINV) management guideline. In patients treated with highly emetogenic chemotherapy in general clinical settings, triple therapy with a serotonin (5-hydroxytryptamine-3 [5-HT3]) antagonist (preferably palonosetron), dexamethasone, and aprepitant is recommended for acute CINV prevention. In resource-restricted settings, triple therapy is still recommended, although a 5-HT3 antagonist other than palonosetron may be used. In both general and resource-restricted settings, dual therapy with dexamethasone (days 2 to 4) and aprepitant (days 2 to 3) is recommended to prevent delayed CINV. In patients treated with moderately emetogenic chemotherapy, dual therapy with a 5-HT3 antagonist, preferably palonosetron, and dexamethasone is recommended for acute CINV prevention in general settings; any 5-HT3 antagonist can be combined with dexamethasone in resource-restricted environments. In general settings, for the prevention of delayed CINV associated with moderately emetogenic chemotherapy, corticosteroid monotherapy on days 2 and 3 is recommended. If aprepitant is used on day 1, it should be continued on days 2 and 3. Prevention of delayed CINV with corticosteroids is preferred in resource-restricted settings. The expert panel also developed CINV management guidelines for anthracycline plus cyclophosphamide combination schedules, multiday cisplatin, and chemotherapy with low or minimal emetogenic potential, and its recommendations are detailed in this review. Overall, these regional guidelines provide definitive guidance for CINV management in general and resource-restricted settings. These consensus recommendations are anticipated to contribute to collaborative efforts to improve CINV management in Southeast Asia.

The review is devoted to the analysis of the relationship between a chemical structure and properties of low-molecular weight inhibitors of furin, the most studied proprotein convertase, which is involved in the development of some pathologies, such as oncologic diseases, viral and bacterial infections, etc. The latest data concerning the influence of peptides, pseudo-peptides, aromatic and heterocyclic compounds, some natural ones such as flavonoids, coumarins, and others on enzyme inactivation are considered. The power of furin inhibition is shown to rise with the increasing number of positively charged groups in the structure of these compounds. Peptidomimetics (Ki = 5-8 pM) are shown to be the most effective furin inhibitors. The synthesized substances, however, have not been used in practical application yet. Nowadays it is very important to find more selective inhibitors, improve their stability, bioavailability and safety for the human organism.

Thermal therapy combined with chemotherapy is one of the advanced and efficient methods to eradicate cancer. In this work, we fabricated magnetically actuated smart textured (MAST) fibrous systems and studied their candidacy for cancer treatment. The polycaprolactone-Fe3 O4 based MAST fibers were fabricated using electrospinning technique. These MAST fibrous systems contained carbogenic quantum dots as a tracking agent and doxorubicin hydrochloride anticancer drug. Additionally, as fabricated MAST fibrous systems were able to deliver anticancer drug and heat energy simultaneously to kill HeLa cells in a 10 min period in vitro. After treatment, the metabolic activity and morphology of HeLa cells were analyzed. In addition, the mechanism of cell death was studied using flow cytometry. Interestingly, the navigation of these systems in the fluid can be controlled with the application of gradient magnetic field. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 40-51, 2018.

To evaluate potential hepatic metabolism-mediated drug interactions with fucoidan from Undaria pinnatifida (UPF) or Fucus vesiculosus (FVF) and potential growth inhibition activity with either fucoidan alone or with chemotherapy. In vivo studies were done to confirm safety and investigate fucoidan-mediated immune modulation.

To observe the effectiveness of grain-moxibustion in resisting oxidative stress in doxorubicin (DOX)-induced cardiomyopathy rats.

Hexavalent chromium (Cr (VI)) is a common environmental pollutant. Cr (VI) exposure can lead to severe damage to the liver, but the preventive measures to diminish Cr (VI)-induced hepatotoxicity need further study. S-allyl cysteine (SAC) is a constituent of garlic ( Allium sativum) and has many beneficial effects to humans and rodents. In this study, we intended to analyze the mechanistic role of SAC during Cr (VI)-induced hepatotoxicity. Male Wistar albino rats were induced with 17 mg/kg body weight to damage the liver. The Cr (VI)-induced rats were treated with 100 mg/kg body weight of SAC as an optimum dosage to treat hepatotoxicity. We observed that the levels of oxidants, lipid peroxidation and hydroxyl radical (OH•) were increased, and enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were found to be decreased in Cr (VI)-induced rats. While treated with SAC, the levels of oxidants were decreased and enzymatic antioxidants were significantly ( p < 0.05) increased. Lysosomal enzyme activities were increased in Cr (VI)-induced rats and on treatment with SAC, the activities were significantly decreased. The expressions of nuclear factor-kappa B (p65-NF-κB), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) were increased during induction with Cr (VI). Subsequent administration of SAC to animals showed a decrease in the expressions of NF-κB, TNF-α, and iNOS. Results obtained from this study clearly demonstrated that SAC protects the liver cells from the Cr (VI)-induced free radical damage.

The present study was designed to explore whether yam could protect the heart from doxorubicin (DOX)-induced oxidative stress leading to cardiotoxicity in vivo. In this study, the protective effects of water and ethanol extracts of three varieties of yam, including water extracts of Dioscorea japonica Thunb., ethanol extracts of D. japonica Thunb., water extracts of Dioscorea alata, ethanol extracts of D. alata, water extracts of Dioscorea purpurea, and ethanol extracts of D. purpurea, against DOX-induced cardiotoxicity in experimental mice were evaluated. DOX treatment led to significant decreases in the ratio of heart weight to body weight and heart rate, and increases in blood pressure and the serum level of lactate dehydrogenase, a marker of cardiotoxicity, were recovered by yam extracts, especially in water extracts of D. alata. Yam extracts also decreased the cardiac levels of thiobarbituric acid relative substances, reactive oxygen species, and inflammatory factors, as well as the expression of nuclear factor kappa B, while ethanol extracts of D. japonica Thunb. and D. purpurea were shown to be more potent. Moreover, yam extracts had a role in increasing the activities of glutathione peroxidase and superoxide dismutase, thus improving the DOX-induced alterations in oxidative status in the heart tissue of DOX-treated mice. All ethanol extracts of yam exhibited their antiapoptotic abilities on caspase-3 activation and mitochondrial dysfunction, and ethanol extracts of D. alata still exerted a superior effect. Based on these findings, it can be concluded that yam has significant cardioprotective properties against DOX-induced damage via its multiple effects on antioxidant, anti-inflammatory, or antiapoptotic activities.

A target cell extraction-chemical profiling method based on human alveolar adenocarcinoma cell line (A549 cells) and UHPLC/LTQ Orbitrap MS for screening the anti-lung cancer bioactive compounds from Curcuma longa has been developed in this paper. According to the hypothesis that when cells are incubated together with the extract of Curcuma longa, the potential bioactive compounds in the extract should selectively combine with the cells, then the cell-binding compounds could be separated and analyzed by LC-MS. The bioactive compounds in C. longa are lipophilic components. They intend to be absorbed on the inner wall of cell culture flask when they were incubated with A549 cells, which will produce interference in the blank solution. In this paper, by using cells digestion and multi-step centrifugation and transfer strategy, the interference problem has been solved. Finally, using the developed method, three cell-binding compounds were screened out and were identified as bisdemethoxycurcumin, demethoxycurcumin, and curcumin. These compounds are the main bioactive compounds with anti-lung cancer bioactivity in C. longa. The improved method developed in this paper could avoid the false positive results due to the absorption of lipophilic compounds on the inner wall of cell culture flask, which will to be an effective complementary method for current target cell extraction-chemical profiling technology.

In recent years, the green microalgae Neochloris oleoabundans have demonstrated to be an interesting natural source of carotenoids that could be used as potential food additive. In this work, different N. oleoabundans extracts obtained by pressurized liquid extraction (PLE) have been analyzed in depth to evaluate the influence of different culture conditions (effect of nitrogen, light intensity or carbon supplied) not only on the total carotenoid content but also on the carotenoid composition produced by these microalgae. Regardless of the cultivation conditions, lutein and carotenoid monoesters were the most abundant carotenoids representing more than 60% of the total content in all extracts. Afterwards, the effect of the different N. oleoabundans extracts and the dose-effect of the most potent algae extracts (namely, N9, PS and CO2 (-)) on the proliferation of human colon cancer cells lines (HT-29 and SW480) and a cell line established from a primary colon cancer cell culture (HGUE-C-1) were evaluated by an MTT assay whereas a stepwise multiple regression analysis was performed to get additional evidences on the relationship between carotenoid content and the antiproliferative activity. Results revealed that, as a general trend, those extracts with high total carotenoid content showed comparably antiproliferative activity being possible to establish a high correlation between the cell proliferation values and the carotenoid constituents. Monoesters showed the highest contribution to cell proliferation inhibition whereas lutein and violaxanthin showed negative correlation and diesters and zeaxanthin showed a positive significant contribution to cell proliferation.

Kaempferol, a natural flavonoid, has been shown to induce cancer cell apoptosis and cell growth inhibition in several tumors. Previously we have conducted a full investigation on the chemical constituents of Gynura medica, kaempferol and its glycosides are the major constituents of G. medica. Here we investigated the growth inhibition and apoptosis induction effect of kaempferol extracted from G. medica.

Sijunzi Decoction (SD) is a traditional Chinese medicine which is composed of Ginseng, Atractylodes, Poria and Licorice. It is one of the commonly used Chinese traditional medicines that showed anti-gastric cancer activity in clinical studies. Previous evidence demonstrated SD parties (Ginseng, Atractylodes, Poria, Licorice) can inhibit proliferation and induced apoptosis for gastric cancer cell. In order to further investigate the anticancer effect of SD in gastric cancer, we observed the effects of different concentrations of SD on proliferation and apoptosis of Side Population Cells (SP) of human gastric cancer SGC-7901.

Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals. In vitro study exhibited effective antitumor activity of α-tocopherol on ORL-48 at 2.5 ± 0.42 µg/mL. Cisplatin exhibited stronger activity at 1.0 ± 0.15 µg/mL, but unlike α-tocopherol it exhibited cytotoxicity on normal human epidermal keratinocytes at very low concentration (<0.1 µg/mL). Despite the lower potency of α-tocopherol, signs of apoptosis such as the shrinkage of cells and appearance of apoptotic bodies were observed much earlier than cisplatin in time lapse microscopy. No apoptotic vesicles were formed with cisplatin, instead an increased population of cells in the holoclone form which may suggest different induction mechanisms between both agents. High accumulation of cells in the G0/G1 phase were observed through TUNEL and annexin V-biotin assays, while the exhibition of ultrastructural changes of the cellular structures verified the apoptotic mode of cell death by both agents. Both cisplatin and α-tocopherol displayed cell cycle arrest at the Sub G0 phase. α-tocopherol thus, showed potential as an antitumour agent for the treatment of oral cancer and merits further research.

Malignant glioblastoma multiform (GBM) is the most common primary malignancy of the brain in the U.S. Temozolomide (TMZ) is the cornerstone of management along with surgical resection and radiotherapy. Because of the reduction in the CD4+ lymphocyte count as a side effect of TMZ use, this patient population is under risk for opportunistic infections like Pneumocystis jiroveci. A male patient with newly diagnosed glioblastoma multiform presented with non-productive cough and chest pain. Before presentation, the patient received the standard therapy including surgical resection, radiation and TMZ. Computerized tomography of the chest showed a very large cavitary lesion in the upper segment of the right lower lobe and multiple nodular lesions with some starting to cavitate. Cytology of the bronchioalveolar lavage with special stain showed large, broad based budding yeast-like cells, morphologically consistent with blastomyces and macrophages filled with yeast-like forms, morphologically consistent with histoplasma. The patient was treated with intraconazole intended for 12 months. To the best of our knowledge, our case represents the first documented case of lung infection with both blastomyces and histoplasma in a patient after receiving TMZ for newly diagnosed GBM.

Controversy exists whether Leydig cells recover after testicular cancer (TC) treatment or whether premature hormonal aging will occur.

Markers able to predict the response to antiangiogenics in metastatic clear cell renal cell carcinoma (ccRCC) are not available. The development of new treatment options like immunotherapy are reaching the clinic; therefore, predictors of benefit from these different available treatments are increasingly needed.

Parallel development of preclinical models that recapitulate treatment response observed in patients is central to the advancement of personalized medicine.