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Volume 8, Emitir 11 (2016)

Artigo de Pesquisa

Antiproliferative Activity of Kenyan Trametes versicolor Aqueous Extract on Selected Cancer and Normal Cell Lines

Chengo JK, Adipo N, Kiboi DM, Lusweti JM, Mwatha J, Mwitari PG, Ngule CM and Njagi SM

Cancer is a major public health burden in both developed and developing countries. The current conventional cancer therapies like chemotherapy are expensive and inaccessible to many cancer patients. Commercial and wild edible mushrooms are becoming more important for their nutritional value and are becoming an alternative source of immune modulation and anticancer agents. Although Previous studies with Trametes versicolor mushroom from various parts of the world have demonstrated antiproliferative activity on various cancer cell lines, the antiproliferative activity of the recently identified Kenyan T. versicolor mushroom have not been studied. This study examined the in vitro antiproliferative activity of an aqueous extract of the Kenyan T. versicolor mushroom on breast cancer (4T1), prostate cancer (DU145), hepatocellular carcinoma (HCC), rat normal intestinal epithelial cells (IEC-6) and African green monkey normal kidney (vero) cell lines using MTT assay. The results demonstrated that the T. versicolor extract at 1.37 μg/ml to 1000 μg/ml dose-dependently inhibited the proliferation of DU145 and 4T1cell lines with IC50 values: DU145 (71.2 μg/ml) and 4T1 (188.5 μg/ml). The extract however did not exert any significant antiproliferative effect on HCC, IEC-6 and Vero cell lines (IC50˃1000 μg/ml) when compared with a chemotherapeutic anticancer drug, tamoxifen (p<0.05), confirming the tumor-selective cytotoxicity on cancer cell lines and its safety on normal cell lines. In all cell lines, the extract showed a significant difference in inhibition of cell proliferation between the untreated cells and the highest concentration (1000 μg/ml) (p<0.05). Presence of phytochemicals such as saponins, tannins, steroids, terpenoids and flavonoids in the T. vesicolor extract used might be the probable reason for its antiproliferative activity.

Artigo de Pesquisa

Effect of Sevoflurane Preconditioning on Inflammatory Cytokines and Oxygen Radicals During Single Lung Ventilation in Patients with Lung Cancer

Hao Zhang, Yilu Zhou, Yinglin Wang and Qingxiu Wang

Objective: To observe the effect of sevoflurane preconditioning on inflammatory cytokines and oxygen radicals during single lung ventilation (SLV) in patients with lung cancer and to discuss the mechanism of sevoflurane induced lung protection.

Methods: Thirty patients, ASA I or II, with non-small-cell lung cancer underwent pulmonary surgeries were randomized into two groups: sevoflurane preconditioning group (group S, n=15) and control group (group C, n=15). After general anaesthesia induction. A double-lumen tube was placed and the position was checked by a fibre optic bronchoscope. During the mechanical ventilation, patients in group S, received sevoflurane at 1.0 minimum alveolar concentration (MAC) for 30 min as a preconditioning and then replaced by oxygen for a complete rapid gas exchange to reduce the sevoflurane inhalation concentration to 0 before SLV. While in group C, only intravenous anaesthetic agents, fentanyl and propofol, were administrated before SLV. Blood concentrations of TNF-α, IL-6, IL-8, SOD and MDA were measured at Post-induction of anaesthesia (T1), 30 min after SLV in the lateral position (T2), 60 min after SLV in the lateral position (T3), and at the end of the operation (T4).

Results: When compared with Tl, the concentrations of TNF-α, IL-6 and MDA in both groups and the IL-8 in group S were significantly increased at T2-T4 (P<0.05), while the expression of SOD in two groups were decreased significantly(P<0.05). The concentrations of TNF-α, IL-6, IL-8 and MDA in group S were decreased significantly at T2-T4 (P<0.05 or P<0.01) when compared with those in group C. The activity of SOD in group S was significantly increased at T3 and T4 (P<0.05).

Conclusion: Sevoflurane preconditioning may moderate the release of inflammatory cytokines to inhibit the inflammatory reaction and may reduce the lipid peroxidation by inhibiting the generation of oxygen free radical. It may protect the lung from the injury during SLV.

Artigo de Pesquisa

Severe Liver Toxicity in a Lung Cancer Patient Treated with Erlotinib: A Case Report and Literature Review

Yi-Chun Lai and Jiun-I Lai

Background: Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) constitute the standard therapy for advanced stage non-small cell lung cancer. Compared with systemic chemotherapy, TKI based treatment has fewer adverse effects.

Patients and methods: We present a lung cancer patient with erlotinib associated severe liver toxicity and perform a systemic review on published studies that report EGFR-TKI-associated liver toxicity. We conducted a systemic search in Medline, PubMed, and Google for studies that were accessible.

Results: A total of 18 papers was found from which we analysed 16 studies with a total of 30 patients. This is the largest case numbers literature review. In these studies, abnormal liver function levels were reported around 75.4 ± 135.2 days after initiating EGFR- TKI treatment. Six patients (20%) died during the study period (23.8 ± 22.5 days after EGFR-TKI use) who were more likely to be Male, to use erlotinib, to receive EGFR- TKI as non-first line therapy, and to have liver metastasis.

Conclusion: From our analysis, male, erlotinib use, EGFR-TKI for second line or later use, and initial liver metastasis were associated with higher mortality after EGFR-TKI-associated liver toxicity. The underlying mechanism is unknown, and further studies are required to validate these results.

Artigo de Pesquisa

A Clinical Phase II Study of Oral Vinorelbine in HER-2 Negative Metastatic Breast Cancer

Rasha Abd El-Ghany Khedr* and Amr Abd El-Aziz Ghannam

Background: Oral vinorelbine, produce an effective and viable treatment option in both the first and secondline settings for patients with metastatic breast cancer (MBC). The present phase II single institution study designed with an aim to analyze the efficacy and safety of oral vinorelbine as first-line therapy for patients with metastatic breast cancer (MBC)

Patients and methods: Twenty-one women aged >18 years with histopathologically confirmed HER-2 negative MBC, were enrolled to receive oral vinorelbine given as a single agent at doses of (60 mg/m2, day 1 and 8 of a 3-week cycle and thereafter 80 mg/m2 of days 1 and 8). No prior chemotherapy was allowed for treatment of metastatic disease, patients who received oral vinorelbine as adjuvant or neoadjuvant therapy were excluded.

Results: Objective response was observed in 28.7% of patients (6/21), and tumour control rate was 66.8% (14/21). Only one patient (4.8%) experienced complete response following treatment. The median progressionfree survival (PFS) and overall survival (OS) were 6 and 16 months, respectively. The 1-year OS and PFS rates were 64.1% and 16.2%, respectively. Most adverse events were mild to moderate. The most common grade 3/4 hematological toxicities were neutropenia (9.5%), while the most common grade 3/4 non-hematological toxicities were nausea/vomiting (14.3%). No treatment-related mortality was noted in this cohort.

Conclusion: Oral vinorelbine as first-line therapy in patients with MBC appeared to offer an acceptable clinical profile and easy to administer in outpatients. The substitution of oral vinorelbine for intra-venous form is not only feasible, but may be in the patients’ best interest.

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