
Background and Objective: The involvement of haemostasis in lymphoid malignancy is of great importance.Thrombosis may occur as a result of some lymphoid malignancies and chemotherapeutic agents used.Therefore, the study aimed to evaluate some haemostatic functional changes such as platelet counts and factor V in lymphoid malignant patients on chemotherapy to determine their clinical significance.Materials and Methods: It was a prospective study carried out in a tertiary hospital in Benin City, Edo State.A total of 60 patients, comprising of 20 lymphoid malignant patients on chemotherapy, 20 novel lymphoid malignant patients and 20 controls participated in the study.Factor V analysis using the one-stage method and platelet count analysis using the electronic impedance principle in the haematology analyzer was done.Results: The results revealed that there was a significant decrease of coagulation factor (p<0.001) and a significant increase in platelet count (p<0.05) for the comparison of novel lymphoid malignant patients and the control group.Furthermore, for lymphoid malignant patients on chemotherapy, there was a significant decrease of coagulation factor (p<0.05) and not significant for platelet count (p>0.05)compared with control.However, there was no significance for factor V (p>0.05) and platelet count (p>0.05) for lymphoid malignant patients on chemotherapy and novel lymphoid malignant patients.Conclusion: The results showed that lymphoid malignancy is associated with the haemostatic disorder and that chemotherapy had a therapeutic effect on the platelets and not on factor V. For effective management of the lymphoid malignant patients, there should be routine screening for all the specific single coagulation factors assay and platelet count before the commencement of the chemotherapy.
Background and Objective: Palladacycles have been reported to exert significant anticancer activities against different cancer cells.The current study conducted to evaluate the anti-tumor activity of a new palladacycle complex (ASH10) in estrogen receptor-positive (MCF7) and triple-negative (HCC1937) breast cancer cells.Materials and Methods: The effect of ASH10 on cell proliferation was tested by MTT assay.Scratch assay was used to test the anti-migration ability of ASH10.Apoptosis induced by ASH10 was measured by different methods including nuclear staining and detection of apoptosis markers by western blotting.Autophagy induced by ASH10 also measured by LC3II puncta staining and western blotting using the LC3II antibody.Results: The MTT results showed that the ASH10 compound has a strong anti-growth effect.Data showed that ASH10 induces its cytotoxic effect by inducing DNA damage followed by cell cycle arrest, intrinsic apoptosis and autophagy.Compared to untreated cells, ASH10 treated cells showed high levels of DNA damage markers p-H2AX, p-ATM and p53.Importantly, the cell cycle arrest marker p21 was similarly induced by ASH10 treatment.Furthermore, ASH10 induced significant levels of apoptosis as evidenced by nuclear fragmentation and an increase in the levels of PARP cleavage.Interestingly, ASH10 also activated the formation of autophagosomes and increased the autophagy marker LC3II.Inhibition of autophagy led to a decrease in ASH10 cytotoxicity suggesting that ASH10 induced autophagy was a cytotoxic mechanism.Conclusion: These results demonstrated that ASH10 is a potential effective compound in the treatment of both ER-negative and ER-positive breast cancer cells.
Background and Objective: Microalgae are the vital constituents in food chains of aquatic ecosystems and have been used for human consumption as food and as medicines.The wide diversity of compounds synthesized from different metabolic pathways of fresh water algae provides promising sources of secondary metabolites in the form of phytochemical constituents.These metabolites are very interesting source of producing an herbal medicine to treat diseases like cancer which is a major public health concern.The study aims to determine the phytochemical constituents, antioxidant and anti-cancer activities of Tetradesmus acuminatus algal extraction MCF-7 human breast cancer cell line.Materials and Methods: The dried and dehydrated algae biomass was subjected to extraction by cold maceration method using 5 solvents of increasing polarity from a non-polar (hexane) to a more polar solvent (aqueous).Phytochemical screening was done using different biochemical tests.Quantitative analysis for phenol was determined by Folin-Ciocalteu reagent method.The antioxidant activity was tested using 2, 2-diphenyl-1-picrylhydrazyl, ferric ion reducing power assay.In vitro anti-cancer activity on MCF-7 human breast cancer cell line was evaluated by (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) MTT assay.Results: The phytochemical analysis revealed broad spectrum of bioactive compounds including flavonoids, glycosides, phenols, tannins, fats and oils.Methanol and aqueous extracts exhibited higher phenolic content as compare to ethanol extract.Antioxidant capacities were shown highest in methanol and ethanol aqueous based on the test performed.The methanol and aqueous extracts were found to be selectively cytotoxic in vitro to on MCF-7 human breast cancer cell line with IC 50 values 468.31±24.15and 598.12±12.18µg mLG 1 for MCF-7, respectively, while it had no cytotoxic effect on normal mice embryo fibroblast cells. Conclusion:The results indicate that Tetradesmus acuminatus was a promising antioxidant and anti-cancer agent for MCF-7 human breast cancer cell line.However, further studies are needed to conclude its therapeutic use.
Background and Objectives: Several studies have been investigated the natural components as an alternative cancer therapy.This study aimed to address the antitumor efficacy of Prunus armeniaca seed extract (PASE) and Prunus domestica seed extract (PDSE).Materials and Methods: Phytochemical analysis and gas chromatography-mass spectroscopy (GC-MS) profile, human breast (MCF-7), hepatic (HepG-2) cancer cell lines and Ehrlich ascetic carcinoma (EAC) were used to determine the anticancer efficacy.Results: Total phenolic, flavonoids, saponin and anthocyanin in PASE were 1291 µg mLG 1 , 159 µg mLG 1 , 16 mg gG 1 and 65 µg mLG 1 , respectively.While, in PDSE were 729 µg mLG 1 , 63 µg mLG 1 , 7.6 mg gG 1 and 89 µg mLG 1 , respectively.The GC-MS analysis showed that the highest peak area (%) in PASE was octasiloxane-hexadecamethyl (17.04%) and in PDSE was hexadecanoic acid, trimethylsilyl ester (31.92%).In vitro inhibition concentration (IC 50 ) of PASE and PDSE against MCF-7 were 31.5 and 306, respectively.The IC 50 of PASE and PDSE against HepG-2 were 22.8 and 430 µg mLG 1 , respectively.The PASE had a potent anticancer activity higher than PDSE against EAC-bearing mice.Conclusion: PASE had a potent anticancer activity than PDSE due to their phytochemicalʼs contents.
Background and Objective: MicroRNAs had been implicated in several malignancies.Abnormal circulating microRNA-1246 expression had been detected in HCC patients in an expanding number of studies.However, the information in literature describing the pertinent ramifications of miR-1246 in early-stage HCCs are rare and heterogeneous.This study was designed to assess the diagnostic accuracy of serum miR-1246 level in early-stage HCV-related HCC patients contrasted with chronic hepatitis C (CHC), liver cirrhosis (LC) and healthy control (HC).Materials and Methods: Two hundred HCV outpatients were doled out into 3 groups, HCC group (n = 100), CHC group (n = 30) and LC group (n = 70).Another hundred (100) age-and sex-matched healthy controls (HC) were likewise enlisted.The serum expression level of miR-1246 (by quantitative Real-Time PCR), AFP and prothrombin induced by vitamin K absence-II (PIVKA-II) were tested.Results: In HCC patients, in contrast to AFP, the serum expression levels of PIVKA-II and miR-1246 were statistically significantly increased discriminating HCC patients and early-stage HCCs not only from non-HCC patients (CHC, LC) yet additionally from HC. PIVKA-II and miR-1246, either individually or combined, had excellent diagnostic accuracies and performances as demonstrated by their ROCs and high AUCs >0.7.This serum over-expression positively correlated with the clinicopathological characteristics of both HCC and non-HCC patients.Conclusion: Serum miR-1246 level was significantly higher in HCC patients compared with non-HCC and HC and reliably discriminate early-stage HCV-related HCCs particularly when combined with PIVKA-II.
Background and Objectives: Plant and marine extracts remain popular subjects for drug development.Exploring the potential of endemic Philippine plants as sources of cytotoxic compounds, this study looked into the cytotoxicity of Garcinia rubra Merr.against selected human cancer cell lines.Materials and Methods: Sub-fractions from the ethyl acetate fraction of G. rubra leaf were generated using vacuum liquid chromatography.Cytotoxicity of the fractions against colorectal, breast and lung adenocarcinoma cell lines was assessed and the most toxic sub-fraction was screened for selected hallmarks of apoptosis.Its selectivity for cancer was then determined.Moreover, the potential of the most active sub-fraction to act in synergism with doxorubicin was assessed using combinatorial assay.Lastly, the phytochemical constituents of the sample were screened.Results: Fractions 6, 7, 8 and 9 were active against the cancer cell lines tested.Fraction 7 induced apoptosis against colorectal cancer cells, but was not selective against cancer cells.It also proved to act synergistically with doxorubicin, allowing even sub-lethal concentrations to induce cell death.Lastly, phytochemical screening showed that the active fraction contained condensed tannins and phenolic compounds.Conclusion: Garcinia rubra was established to be a good source of cytotoxic and pro-apoptotic compounds.
Background and Objectives: Doxorubicin is an efficient anti-neoplastic drug but its clinical usefulness is limited by its serious adverse effects such as cardiotoxicity.The main objective of this research was to investigate whether natural marine astaxanthin could chemosensitize the Ehrlich ascites carcinoma cells to the anti-tumor effect of doxorubicin.Materials and Methods: Survival of Ehrlich ascites carcinoma bearing mice was used as model to evaluate the chemosensitizing effect of astaxanthin to doxorubicin cytotoxicity.After treatment with doxorubicin and/or astaxanthin, doxorubicin uptake was measured by spectrofluorometric assay, apoptosis and the cell cycle phase distribution were determined by flow cytometry analysis and P53 gene expression was also studied in the EAC cells.Results: Treatment of tumor bearing mice with doxorubicin showed a significant increase in the mean survival time to 32.5 days with 30% long-term survivor.Treatment of the tumor-bearing animals with astaxanthin and doxorubicin showed a significant increase in the mean survival time to 41.1 days with 80% long-term survivor.Doxorubicin cellular uptake was increased significantly after astaxanthin treatment.Moreover, astaxanthin treatment dramatically increased the early apoptosis and G 2 /M phase accumulation after addition to doxorubicin.P53 gene expression was up regulated after doxorubicin treatment, moreover addition of astaxanthin synergized the action of doxorubicin where p53 gene expression was highly upregulated.Conclusion: The present study concluded that the marine astaxanthin potentiates the cytotoxic activity of doxorubicin against the growth of mammary tumor cells in vivo through accumulation of the tumor cells in G 2 /M phase , induction of apoptosis and up regulation of the tumor suppressor p53 gene expression.
Background and Objective: Cluster of differentiation (CD) 74 is well known for its diverse proinflammatory and immunological functions.This study was undertaken to investigate the role of interferon (IFN)-γ on CD74 expression in breast cancer cells.Materials and Methods: The CAMA-1 and MDA-MB-231 cancer cells were stimulated with IFN-γ and expression of CD74 was determined by flow cytometry and western immunoblotting using Raji cells as a positive control.The MTT assays were used to determine the effect of IFN-γ on the proliferation and migration of cells.Whereas, cell surface expression of HLA-ABC and HLA-DR were acquired by flow cytometry.Results: Treatment of CAMA-1 and MDA-MB-231cells with IFN-γ significantly increased the expression of CD74.Not only have these, IFN-γ also stimulates the expression of HLA-ABC and HLA-DR in a dose-dependent manner in CAMA-1 and MDA-MB-231cells.Moreover, IFN-γ treatment also inhibited the proliferation and migration of CAMA-1 and MDA-MB-231cells.Conclusion: The IFN-γ up-regulates CD74 expression in human breast cancer cells.The results concluded that IFN-γ played a key role in modulating the expression of CD74, as well as in the proliferation and the migration of CAMA-1 and MDA-MB-231 cancer cells.Data suggest that CD74 plays a key role in tumor immunogenicity as well as in breast cancer immunoediting in humans.
Background and Objective: Evidence of the relationship between malnutrition and the systemic inflammatory process is growing, a condition in the cancer patient that may be even more exacerbated.This study aimed to evaluate the relationship between NLR and the presence of malnutrition in patients with cancer and verify the association of nutritional status evaluation with objective and subjective methods.Materials and Methods: Descriptive cross-sectional study conducted with adult and elderly individuals of both sexes with diagnosis of GI and adnexal gland cancer evaluated during the first 48 h of hospital admission.The nutritional status was evaluated through classical anthropometric and biochemical variables as well as subjective global assessment (SGA).The percentage of weight loss (% WL) at 6 months, the Nutritional Risk Index (NRI) and the NLR with cut-off points defined for this study >3 were calculated.Association and correlation tests were applied.The significance level adopted for the tests was 5%.Results: The 87 patients were included, mean age 57.3±15.3years.The SGA identified 73.6% of malnutrition patients of varying degrees and 46.0%presented with weight loss greater than 10.0% in 6 months.Regarding NLR, 55.2% of the patients presented values above the recommended cut-off point.There was an association of NLR with %WL (p = 0.002) and SGA (p = 0.009).Serum levels of albumin and total protein and the NRI were inversely correlated with NLR (p<0.005), while a positive correlation was observed with PP % (p = 0.008).Conclusion: The NLR was associated with varying degrees of malnutrition indicated by SGA, high weight loss and nutritional risk according to the NRI, with the possibility of being a useful and complementary marker in nutritional evaluation.
Background and Objective: The anti-neoplastic activities of metformin were investigated in many pre-clinical and clinical studies.In this study, metformin which is familiar oral drug, cheap and available in all places was used to evaluate its efficacy in Egyptian patients with advanced prostate cancer.Materials and Methods: Twenty six patients with advanced prostate cancer either treatment naïve or previously treated were subjected to metformin therapy.Metformin was administered as glucophage1000 mg twice daily concomitantly with standard of care treatment continuously till disease progression, drug toxicity or patient refusal.Results: The median age of studied patients was 65 years, range 59-75 with median body mass index 24.75range 17-40, 18 cases had ECOG PS of one and the remaining cases were ECOG 2. Out of 26 patients, 17 were treatment naïve while 9 of them were subjected to previous SOC treatment.The overall response (CR, PR) was 53.8%, no response (SD, PD) represented 46.2% and the median time to tumor progression (TTP) was 18 weeks but it was significantly different in previously treated cases and treatment naive cases, in which median TTP in previously treated case was 8 weeks compared to 32 weeks in treatment naïve cases [p<0.001,HR (95%CI) 12.326 (3.212-47.306)].Conclusion: Metformin was well tolerated and had encouraging results for patients with advanced prostate cancer.
Background and Objective: Short chain free fatty acids (SCFAs) like butyrate, propionate and acetate are produced by microbiota in the gut.SCFAs have been shown to exert their metabolic effects through their cognate receptors (FFAR2 and FFAR3).These receptors are abundantly expressed in colonic epithelium and several studies have shown that these receptors play an important role in the metabolic homeostasis of colonic epithelial cells and are possibly involved in colorectal carcinogenesis.This study was initiated to understand the role of FFAR3 gene in colorectal cancer cell growth and proliferation.Materials and Methods: The HCT116 colorectal cancer cell line was engineered to develop stable FFAR3 knockdown using shRNA mediated gene silencing technology.Down regulation of FFAR3 mRNA was confirmed by RT-PCR and consequences of FFAR3 down regulation on cell growth and proliferation were analyzed.Results: The data revealed that FFAR3 down regulation had no impact on proliferation and growth rate of engineered HCT116 cells.Moreover, FFAR3 knockdown cells did not show any difference in the glucose uptake rate or cyclic adenosine monophosphate (cAMP) levels as compared to control cells.The most likely explanation of lack of FFAR3 effect on HCT116 cell metabolism was that FFAR2 compensated for the loss of FFAR3 and maintained the functionality of SCFAs.Conclusion: This study showed that FFAR3 gene alone does not impact growth and cell proliferation of colorectal cancers.Further studies are needed to fully understand the role of FFAR3 by using double knockdown cells (FFAR2/FFAR3).
Background and Objective: Tabernaemontana divaricata belongs to family Apocynaceae is an ornamental, flowering, evergreen shrub that is used in traditional medicine for the treatment of urinary disorders, abdominal tumours and dysentery.The aim of the study was to investigate in vitro antitoxicity and anticancer activities from leaf extracts of Tabernaemontana divaricata. Materials and Methods:The present study involves at screening of preliminary phytochemicals, determination of total phenolic contents, evaluation of methanol, ethanol and aqueous leaf extracts of T. divaricata using in vitro 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) assay, ferric ion reducing antioxidant power (FRAP) assay, Phosphomolybdenum (PM) method and evaluation of in vitro anticancer activity on T-24 human bladder cancer cell line.Results: The preliminary screening of phytochemicals revealed a broad spectrum of secondary metabolites present in all five different solvent extracts.Aqueous extract showed high presence of phenols (62.54±0.18mg gG 1 GAE, r 2 = 0.9882) among methanol and ethanol extracts in comparison to Gallic acid (80.28±0.14mg gG 1 GAE, r 2 = 0.9954).Ethanol extracts exhibited potential antioxidant activity at a concentration of 100 mg mLG 1 (62.41±0.67%).The IC 50 value was 188.9±07 µg mLG 1 for T-24 bladder cancer cell line whiles the standard drug Doxorubicin showed an IC 50 value of 0.23 µM mLG 1 .Morphological variations was observed in cancerous cells undergoing cell shrinkage and membrane blebbing in human bladder cancer cell line T-24 while the extract showed no cytotoxicity towards normal cells MEF-L929.Conclusion: Based on these results it can be concluded that the tested extracts holds significant antioxidant and anticancer properties.However further investigation with lead compounds of T. divaricata on in vivo trials will enable its therapeutic use.
Background and Objective: miR-10b is one of oncogenic miRNA first described in promoting metastases in Breast Cancer.The aim of the study was to investigate the expression of miR-10b and the expression of metastases-induced genes in BC (BC) and fibroadenoma (FA) in West Sumatra.Materials and Method: LNATM primer enhancer set was used to identify the miR-10b expression as a relative quantification.miR-16 was used as an endogenous control with a relative median expression of miR-10b at 2G ))Ct .The expression of metastases-related genes was performed by an absolute quantification method.Results: The statistical differences between miR-10b and the expression of genes were determined by t-student test to interpret the expression of BC and FA tissue (p<0.005).The expression of miR-10b in BC was lower than FA (endogenous control).Relative median of miR-10b expression in BC was 8.51 times lower than FA.Low expression of miR-10b in BC was associated with tissue grading.The expression of metastases-related gene; RhoC, TIMP2 and MMP2 were lower in BC than FA.miR-10b expression differed between BC and FA.Conclusion: RhoC, TIMP2 and MMP2 expression caused cancer cell whether to be metastasized or not.miR-10b is a potential marker to predict BC cell which start to be aggressive.
Background: Leukemia is a cancer of blood cells which treated by different anticancer agents, Plants nowadays considered a new source for the development of new anticancer agent.Euphorbia Lathyris use in folklore to treat skin cancer.Objective Euphorbia lathyris seeds phytochemically investigated then examined its cytotoxic activity against leukemia cells.Materials and Methods: Euphorbia lathyris seed was extracted by maceration with different organic solvents (petroleum ether, chloroform and methanol), each organic extract submitted to phytochemical investigation and evaluated its cytotoxic activity on Leukemic blood with three different doses (50,100 and 150 µg mLG 1 ) and three different intervals.The data were evaluated by two-way analysis of variance (ANOVA).Results: In the present study, the major active constituents for petroleum ether and chloroform fractions were steroids and cholesterol while methanol fraction contains flavonoids as a major active constituent.Percent of inhibition for Petroleum ether and chloroform fractions showed a decrease in the percent of inhibition of leukemic cell proliferation with an increase of time but the same fractions showed an increase in the percent of inhibition with an increase of dose.Methanol fraction showed an increase in the percent of inhibition with increasing the dose and time.Conclusion: It had been concluded that Stepwise fractionation of Euphorbia lathyris offering a separation of active constituents according to polarities, this give a different cytotoxic effect to leukemia cells according to the active constituent that contains.
Background and Objective: Cognitive dysfunction is one of the mental disorders and defined as the impairment in the process of understanding such as knowledge, memory power, attention, analysis, judgment and problem solving etc. Cognitive impairment due to chemotherapy has been reported in 17-75% of patients.Cognitive function can be measured by different subjective and objective assessment techniques.The idea of this systematic review was to appraise the recently published evidence on effect of cancer chemotherapy on cognitive function.The study was designed to evaluate the effect of cancer chemotherapy on cognitive function.Methodology: A comprehensive literature search of articles on the assessment of the effect of cancer chemotherapy on cognitive function was carried out.Based on selection criteria of the study, the articles were reviewed.Cognitive function assessment methods used were different in each of the study article.Results: This review conveyed that the positive correlation between cancer chemotherapeutic regimens and decline in the level of cognitive functioning.It brings out the fact that mechanisms like oxidative stress induced by treatment characteristics like dosage, duration, type of regimen, genetic factors such as ApoE4, COMT-Val, imbalance in cytokines like IL-6,TNF-alpha, IL-1 beta which act as mediating factors for CNS damage, leads to cognitive dysfunction.Patients with any type of cancer, treated with chemotherapy drugs experience a considerable decline in level of cognitive function.Conclusion: Patients with any type of cancer, treated with chemotherapy drugs experience a considerable decline in level of cognitive function.