Crude ethyl acetate extract of marine microalga, Chaetoceros calcitrans, induces Apoptosis in MDA-MB-231 breast cancer cells

Background: Marine brown diatom Chaetoceros calcitrans and green microalga Nannochloropsis oculata are beneficial materials for various applications in the food, nutraceutical, pharmaceutical and cosmeceutical industries. Objective: This study investigated cytotoxicity of different crude solvent extracts from C. calcitrans and N. oculata against various cancer cell lines. Materials and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was carried out to screen the cytotoxic effects of hexane (Hex), dichloromethane (DCM), ethyl acetate, and methanol extract from C. calcitrans and N. oculata toward various cancer cell lines. Flow cytometry cell cycle was used to determine the cell cycle arrest while the mode of cell death was investigated through acridine orange/propidium iodide (AOPI) staining, Annexin V-Fluorescein Isothiocyanate (FITC) and Terminal deoxynucleotidyl transferase-mediated d-UTP Nick End Labeling (TUNEL) assays. Expression profile of apoptotic and proliferative-related genes was then determined using the multiplex gene expression profiler (GeXP). Results: Crude ethyl acetate (CEA) extract of C. calcitrans inhibited growth of MDA-MB-231 cells, with IC 50 of 60 μg/mL after 72 h of treatment. Further studies were conducted to determine the mode of cell death at various concentrations of this extract: 30, 60 and 120 μg/mL. The mode of cell death was mainly apoptosis as shown through apoptosis determination test. The expression data from GeXP showed that caspase-4 was upregulated while B-cell leukemia/lymphoma 2(Bcl-2) was down regulated. Thus, caspase-4 induction endoplasmic reticulum death pathway is believed to be one of the mechanisms underlying the induction of apoptosis while Bcl-2 induced S and G2/M cell cycle phase arrest in MDA-MB-231 cells. Conclusion: CEA extract of C. calcitrans showed the highest cytotoxicity on MDA-MB-231 via apoptosis

ajcr0000117b

Abstract: Cancer is a genetic disease, grows exponentially with the development of intrinsic and acquired treatment resistance. Past decade has witnessed a considerable progress towards the treatment and understanding of proposed hallmarks of cancer and together with advances in early detection and various treatment modalities. Radiation therapy is an integral part of cancer treatment armamentarium. In developed countries more than half of all cancer patients receive radiation therapy during their course of illness. Although radiation damages both cancer and normal cells, the goal of radiation therapy is to maximize the radiation dose to abnormal cancer cells while minimizing exposure to normal cells, which is adjacent to cancer cells or in the path of radiation. In recent years, life expectancy increases among cancer patients and this increase is due to the results of early diagnosis, screening efforts, improved treatments and with less late effects mostly secondary cancer development. Therefore, cancer survivorship issues have been gaining prominence in the area of radiation oncology research. Understanding the tradeoff between the expected decreases in normal tissue toxicity resulting from an improved radiation dose distribution to the targeted site is an increasingly pertinent, yet needed attention and research in the area of radiation oncology. In recent years, a number of potential molecular targets that involve either with radiation increased tumor cell killing or protecting normal cells have been identified. For clinical benefits, translating these findings to maximize the toxicity of radiation on tumor cells while safeguarding early or late normal cell toxicities using molecular targeted radioprotectors will be useful in radiation treatment

Weak expression of cyclooxygenase-2 is associated with poorer outcome in endemic nasopharyngeal carcinoma: analysis of data from randomized trial between radiation alone versus concurrent chemo-radiation (SQNP-01)

<p>Abstract</p> <p>Background</p> <p>Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.</p> <p>Methods</p> <p>58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.</p> <p>Results</p> <p>58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.</p> <p>Conclusion</p> <p>Contrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients.</p

Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC

Retropharyngeal nodal metastasis related to higher rate of distant metastasis in patients with N0and N1nasopharyngeal cancer

Background: Retropharyngeal lymph node (RLN) staging in nasopharyngeal carcinoma (NPC) can be controversial. Methods: We retrospectively reviewed all patients with T2–4, N0–1 NPC treated between 1992 and 1994 to examine if RLN metastasis resulted in an increased incidence of distant metastases. Results: Of the 667 patients with NPC, 395 had T2–4, N0–1 disease, 140 had N0, and 255 had N1. All had staging CT scans and were treated with radiotherapy. Median follow-up was 8.3 years. Seventy-four percent showed undifferentiated histology. In this cohort, 187 (47%) had RLN metastases. Multivariate analysis showed that RLN conferred a higher hazard for distant metastasis (p = .04). Using the Kaplan–Meier method, patients with N0 disease and RLN had a similar hazard for distant metastases as patients with N1 disease when compared with patients with N0 disease and without RLN. Conclusion: Patients with N0 disease and RLN appear to share a similar prognosis to patients with N1 disease. © 2009 Wiley Periodicals, Inc. Head Neck, 200

Presence of a high-grade component in gastric mucosa-associated lymphoid tissue (MALT) lymphoma is not associated with an adverse prognosis

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL) show a spectrum of disease characterized by varying proportions of low-grade and high-grade components. While the natural history and optimum treatment for low-grade gastric MALT lymphoma and DLBCL is well established, the prognosis and optimal treatment of patients with both low- and high-grade components is not well established. The purpose of our study was to evaluate the clinical characteristics, survival outcomes, and prognostic factors of patients with gastric MALT lymphoma and gastric DLBCL. A retrospective review of patients with gastric MALT lymphoma, gastric DLBCL, or MALT lymphoma with a high-grade component treated at our centers from 1994 to 2006 was performed. Patients were divided into three categories: “pure MALT lymphoma,” “MALT lymphoma with high-grade component” (mixed), and “pure DLBCL.” Seventy-six patients were included in our study—26 with pure MALT, 22 with MALT with high-grade component (“mixed”), and 28 with pure DLBCL. Pure MALT lymphoma and mixed lymphoma patients had similar clinical characteristics, whereas pure DLBCL patients had less favorable disease characteristics with significantly poorer performance status, higher number of extranodal sites of disease, higher stage, and larger proportion of bone marrow involvement and international prognostic index (IPI) scores compared with mixed lymphoma. The majority of mixed lymphoma (72.7%) and DLBCL patients (71.4%) were treated with chemotherapy. Of patients receiving chemotherapy, a higher proportion of mixed lymphoma and DLBCL patients received anthracycline-based combination chemotherapy regimens compared with MALT lymphoma (73% vs 71% vs 8%) whereas the proportion of mixed lymphoma and DLBCL patients was similar (p = 0.919). At a median follow-up of 37 months, the 5-year overall survival was 66.9%. The 5-year overall survival was 78% for MALT lymphoma, 84% for mixed lymphoma, and 45% for DLBCL. On univariate analysis, DLBCL histology, age, performance status, serum albumin, lactate dehydrogenase, bone marrow, number of extranodal sites, stage, and IPI score were prognostic for inferior survival. On multivariate analysis, DLBCL histology remained significantly prognostic for inferior survival, independent of chemotherapy regimen (hazard ratio (HR) 6.66, 95% confidence interval (CI) 2.01–21.41, p = 0.001). Mixed histology was not prognostic for inferior survival (HR 1.13, 95% CI 0.28–4.54, p = 0.868). Other factors prognostic for inferior survival were serum albumin <37 g/L (HR 3.22, 95% CI 1.11–13.22, p = 0.034) and treatment with non-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy (HR 4.89, 95% CI 1.67–14.36, p = 0.004). In conclusion, the clinical characteristics of mixed histology MALT lymphoma are similar to low-grade MALT lymphoma and significantly different from pure DLBCL. The prognosis of mixed histology MALT lymphoma is significantly better than pure DLBCL, independent of IPI and chemotherapy regimen, and pure DLBCL histology is independently prognostic of inferior survival outcome

Navigating the challenges of the COVID-19 outbreak: Perspectives from the radiation oncology service in Singapore

10.1016/j.radonc.2020.03.030RADIOTHERAPY AND ONCOLOGY148189-19