Nickel has long been known to have a toxic effect in humans and has been defined as a human carcinogen. However, recent studies have suggested that nickel chloride (NiCl2) may also possess anticancer ...properties. The liver is one of the target organs for nickel, and thus, the present study aims to evaluate the effect of NiCl2 on anticancer biological responses in hepatocellular carcinoma (HCC) cell lines. Both HuH-7, a well-differentiated HCC cell line, and Mahlavu cell line, a poorly differentiated HCC cell line, were exposed to NiCl2. It was determined that NiCl2 decreased cell viability in both cell lines in a dose- and time-dependent manner. Nickel chloride exposure at IC50 doses were observed to suppress the ability of HCC cells to produce colonies and also induce apoptosis of HCC cells by increasing Cleaved Caspase-3 protein levels. It was found that NiCl2 exposure affected cellular morphology, increased the LC3-II protein levels, and induced autophagy in parallel to increased apoptosis in HCC cells. It was also observed that NiCl2 suppressed cell migration, decreased the size and viability of HCC tumor spheroids generated in 3D cell cultures, and disrupted the spheroid structure of the tumor cells depending on E-cadherin expression levels. Furthermore, it was observed that all anticancer biological responses induced by NiCl2 occurred independently of the AKT signaling pathway. In conclusion, our results suggested that NiCl2 induced anticancer biological responses in HCC cell lines. Moreover, this study provided important new molecular and cellular biological basic data about the action mechanisms of NiCl2 in HCC.
Abstract Chemotherapy is used to control and cure cancer by using drugs to destroy cancer cells. Treatment schedules for chemotherapy may vary depending on the type of cancer, the goals of treatment, ...the type of chemotherapy and the patient's state of health. Chemotherapy is usually given in cycles of a treatment-period followed by a rest-period. An oncologist decides the choice of a particular regimen; however, modifications to drug dose and schedule are often necessary because of variabilities in the health of an individual patient. Therefore an orderly execution of chemotherapy regimens requires management, scheduling and allocation of the resources available. Chemotherapy scheduling is an optimization problem. In this paper, a two-phase approach has been adopted to deal with the problem. An adaptive negative-feedback scheduling algorithm is proposed for the first phase to control the load on the system. Two heuristics based on the ‘Multiple Knapsack Problem’ have been evaluated for the second phase to assign patients to specific infusion seats. The overall design has been put to test at a local chemotherapy center and has yielded good results for patient waiting times, orderly execution of chemotherapy regimen and utilization of infusion chairs.
BACKGROUNDThe possible anti-cancer properties of boron, a trace element for humans, have been demonstrated in various experimental and epidemiological studies, although the effects of boron on liver ...cancer are unclear. In the present study we evaluate the effects of boric acid on the cell lines of hepatocellular carcinoma (HCC) of the liver, as the leading form of liver cancer, for which a poorly-differentiated HCC cell line (Mahlavu cell line) was used. METHODSThe anti-cancer effect of boric acid was investigated with a cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques. Also, the effect of boric acid on the AKT signaling pathway was determined through a western blot analysis. RESULTSBoric acid was found to reduce cell viability in a dose- and time-dependent manner, and decreased survival, colony formation ability, migration capability and HCC cell tumor spheroid growth in HCC cell lines, while also inducing apoptosis, autophagy and morphological alteration. Furthermore, boric acid inhibited AKT phosphorylation, and anticancer biological responses in HCC cells were observed only in cells in which AKT phosphorylation was suppressed by boric acid. CONCLUSIONOur results suggest that boric acid might be a promising therapeutic candidate in hepatocellular carcinoma via the inhibition of AKT signaling pathway.
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e21037
Background: There are many drugs that can be applied to the treatment of lung cancer. These therapeutics include classical chemotherapeutics, targeted drugs against driver ...mutations, and immunotherapeutics. However, still, new agents are required to better results and patients outcomes. Recently, imidazole and its compounds, a type of antifungal drugs, were found to have antitumor efficacy in several cancer types. Its effects on non-small-cell lung cancer cells are yet known. This study aimed to detect anti-cancer properties of imidazole on non-small-cell lung cancer cells and suitability for clinical usage as an anti-cancer agent. Methods: We used A549 cell lines that are non-small-cell lung cancer cells in this study. A549 cells were treated with imidazole (molecular grade) at 1, 5, 10, 20, 40, 80 mM doses for 24, 48 and 72 hours. Cytotoxicity and IC50 values (the half-maximal inhibitory concentration) were calculated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis. Colony formation assay was performed to detect the effect of imidazole on cancer cell colony formation ability. The cellular morphological alterations were observed on bright-field microscopy using Giemsa staining. Cellular migration status of A549 cells was defined with in vitro scratch assay up to 48th hour. Results: Cytotoxicity assay results showed that low-level imidazole induced cell proliferation. However, high-level imidazole treatment decreased the cell viability of A549 cells in a dose and time-dependent manner. The IC50 value was calculated as 60 mM, 28 mM, and 15,9 µM doses respectively at 24, 48, 72 hours in A549 cells. Also, we determined that the number of colonies (number of colonies: 42.7 ± 3.06) formed in A549 cell lines treated with imidazole at IC50 dose was statistically less than the colony number of the control group (number of colonies: 70.7 ± 5.13) (p < 0.01). Interestingly, we observed that colony number increased at a low dose (at 5 mM) imidazole treated group, statistically significant (p < 0.05). Cellular morphology was not affected at low doses; however, at the IC50 dose, A549 cells changed their cellular morphology, lost cell-cell contact, decreased cytoplasmic volume, and differentiated from parental morphology. In addition to these effects, we observed that imidazole treated cells decreased their migration capabilities compared with control group cells (p < 0.05). Conclusions: Our results have shown that antifungal imidazole treatment inhibits cancer cell biological responses such as proliferation, colony formation ability, and motility in non-small lung cancer cell lines in a dose and time-dependent manner. These results suggest that imidazole would be the right candidate for the synergy with other therapeutic options such as immunotherapy. This introductory study allows us further studies exploring the synergy and its mechanism.
Background
Imidazole nucleus has been used efficiently in the development of many drug molecules due to its therapeutic effects. Many derivatives of it have been produced particularly for use in ...cancer treatment. However, the anti-cancer effects of imidazole nucleus in liver cancer cells are as yet unclear. In this study, we aimed to investigate the anti-cancer effects of imidazole nucleus in hepatocellular carcinoma (HCC) cell lines.
Methods and results
Anti-cancer effect of imidazole nucleus was investigated using cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques in HuH-7 and Mahlavu cell lines. Also, effect of imidazole on AKT and ERK1/2 pathways were determined using by western blot analysis. Imidazole decreased cell viability in both HCC cell lines in a dose and time-dependent manner and also suppressed the colony forming ability of the cells (p < 0.05). Imidazole increased the cleaved caspase 3 protein levels and thus induced apoptosis (p < 0.05). Imidazole induced morphological alterations and autophagy by increasing intracellular vacuolization. Also, imidazole decreased the viability and dimensions of HCC cell tumor spheroids produced in 3D cell cultures (p < 0.05). Moreover, it was observed that all of these effects, are defined above, appeared in parallel with suppression of AKT and ERK1/2 signaling pathways by imidazole nucleus.
Conclusions
The findings of this present study established the anti-cancer effects of imidazole nucleus in HCC cell lines and showed that it could be a potential molecule in the treatment of HCC via inhibition of AKT and ERK1/2 signaling pathways.
Summary Background There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with ...erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov , NCT01523587. Findings 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1–10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months 95% CI 1·9–2·9 vs 1·9 months 1·9–2·2; hazard ratio HR 0·82 95% CI 0·68–1·00, p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months IQR 13·8–22·4), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months 95% CI 7·2–8·7 vs 6·8 months 5·9–7·8; HR 0·81 95% CI 0·69–0·95, p=0·0077), as were progression-free survival (median 2·6 months 95% CI 2·0–2·9 vs 1·9 months 1·9–2·1; HR 0·81 95% CI 0·69–0·96, p=0·0103) and disease control (201 51% of 398 patients vs 157 40% of 397; p=0·0020). The proportion of patients with an objective response did not differ significantly between groups (22 6% vs 11 3%; p=0·0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 10% vs nine 2%), of grade 3 stomatitis with afatinib (16 4% vs none), and of grade 3 rash or acne with erlotinib (23 6% vs 41 10%). Interpretation The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung. Funding Boehringer Ingelheim.
Pancreatic lipomatosis is characterized as massive lipid infiltration of the pancreatic tissue. Although its etiology is ill defined; obesity, diabetes mellitus, chronic pancreatitis, hereditary ...pancreatitis, and conditions that cause pancreatic ductal obstruction, for example tumors and stones, are related to its pathogenesis. Recently, with the increased use of computerized tomography and magnetic resonance imaging, it has become possible to observe the fat replacement of the pancreas. Herein, we report a 60-year-old man complaining of abdominal pain and weight loss. Preoperative work-up revealed a locally advanced (Stage III) pancreatic adenocarcinoma. Multimodal treatment was carried out and a 100% complete response was detected after neoadjuvant therapy. The patient underwent a standard pancreaticoduodenectomy, without complications. The tissue pathology revealed lipomatosis of the pancreas. He was disease-free and symptom-free at 1 year follow-up. To our knowledge, this is the first report in the literature of pancreatic head carcinoma with total fat replacement of the pancreas after neoadjuvant chemoradiotherapy.
We studied the effect of arsenic trioxide
(As 2 O 3 ) on prostate and ovarian carcinoma cell
lines. As 2 O 3 has been shown to be effective in
leukemia, and acute promyelocytic leukemia in ...particular, both
in vitro and in vivo . As model cell
lines, we used DU145 and PC-3 for prostate cancer and MDAH 2774 for
ovarian cancer. New modalities of treatment are essential in these
kinds of cancers, which produce a high death toll. The
3-(4,5-dimethyl-thiazoyl-2-yl)-2,5diphenyl-tetrazolium bromide
assay was used to evaluate cytotoxicity. Flow cytometric
analysis and mono-oligo nucleosome detection-based ELISA were used to
determine the apoptosis. Isobologram analysis was used to evaluate
synergism and/or the additive effects of As 2 O 3
and conventional chemotherapeutic agents. We clearly demonstrated that
As 2 O 3 has significant cytotoxic effect on both
prostate and ovarian carcinoma cell lines. The dose range of
As 2 O 3 in all three cell lines was∼
10 −6 m . The mechanism underlying
cytotoxicity of As 2 O 3 was shown to be
apoptosis. The experiments by butylated hydroxyanisole showed that the
cytotoxic effect of As 2 O 3 was not through
superoxide generation. There was no synergism, but the additive
effects of As 2 O 3 were demonstrated with
cisplatin, adriamycin, and etoposide. We strongly suggest that
As 2 O 3 alone or in combination with conventional
chemotherapeutic agents be evaluated further as a new agent for the
treatment of prostate and ovarian cancers.
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Background: In women, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Tamoxifen is the most commonly used drug for the ...endocrine treatment of breast cancer. It reduces the risk of recurrence and death from breast cancer when given to estrogen-receptor-positive breast cancer patients. It has recently been shown that imidazoles, an antifungal drug, possess anticancer potentials, and it can be a novel therapeutic in cancer treatment. However, the effects of combined treatment with imidazole and tamoxifen are unknown in estrogen receptor-positive breast cancer cell lines. Our study aimed to investigate the effects of imidazole and tamoxifen combination in estrogen receptor-positive breast cancer cell lines. Methods: MCF7 cell line, an estrogen receptor-positive breast cancer cell line, was used in this study. Following 24 hours 50 mM imidazole (molecular grade) treatment, 15µM tamoxifen was treated to MCF-7 cells by 72 hours. As control groups, following for 24-hour imidazole alone treated, only medium treated cells for 72 hours were used. MTT assay was performed for the determination of cell viability. Apoptosis was shown using acridine orange/ethidium bromide staining. The cellular morphological alterations were observed on bright-field microscopy using Giemsa staining. Cell migration status was determined using by in vitro scratch assay. Results: MTT assay results showed that tamoxifen alone treatment for 72 hours decreased cell viability by 18 percent (p < 0.001). On the other hand, cell viability is not affected by imidazole alone treatment for 24 hours compared with the control group (p > 0.05). However, it was calculated that 24 hours of imidazole followed by tamoxifen for 72 hours decreased cell viability up to 42 percent (p < 0.001). Tamoxifen alone group, compared with combined treatment with tamoxifen and imidazole, observed an increase of apoptotic cell numbers in combined treatment with tamoxifen and imidazole group, statistically significantly (p < 0.01). It was observed that cellular morphology was affected by combined treatment with tamoxifen and imidazole. Giemsa staining results showed that MCF 7 cells changed their cellular morphology, lost cell-cell contact, differentiated from parental morphology and cellular morphology, and appeared unhealthy. Parallel to these findings, a decrease in cell migration was observed in the combined-treated group compared to the tamoxifen alone group (p < 0.01). Conclusions: Our results showed that sequential usage of imidazole followed by tamoxifen has an enhanced anticancer effect of tamoxifen in estrogen receptor-positive breast cancer cell lines. These results allow us to establish a new hormonal treatment for patients with breast cancer.
•Lung cancer is a leading cause of cancer related deaths globally and in MEA.•Surgery remains a gold standard for treatment of resectable NSCLC.•Other treatment modalities include chemotherapy, ...radiotherapy, targeted therapy and immunotherapy.•We recommend use of MDT with a set composition for management of NSCLC in MEA.
The Middle East and Africa (MEA) region, a large geographical area, lies at the confluence of Asian, Caucasian and African races and comprises of a population with several distinct ethnicities. The course of management of non-small cell lung cancer (NSCLC) differs as per patients’ performance status as well as stage of disease, requiring personalized therapy decisions. Although management of NSCLC has received a significant impetus in the form of molecularly targeted therapies and immune therapies in last few years, surgery remains gold standard for patients with early-stage disease. In case of unresectable disease, radiotherapy and chemotherapy are the primary management modalities. With newer therapies being approved for treatment of early stage disease, use of multi-disciplinary team (MDT) for comprehensive management of NSCLC is of prime importance. A group of experts with interest in thoracic oncology, deliberated and arrived at a consensus statement for the community oncologists treating patients with NSCLC in the MEA region. The deliberation was based on the review of the published evidence including literature and global and local guidelines, subject expertise of the participating panellists and experience in real-life management of patients with NSCLC. We present the proposed regional adaptations of international guidelines and recommends the MDT approach for management of NSCLC in MEA.
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