Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity

Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Application Effect of External Diaphragm Pacemaker Combined with Active Respiratory Circulation Technology in Pulmonary Rehabilitation of Perioperative Lung Cancer Patients

Aim: To explore the application effect of external diaphragm pacemaker combined with active respiratory circulation technology in pulmonary rehabilitation of perioperative lung cancer patients. Methods: A total of 98 lung cancer patients admitted to our hospital from April 2020 to November 2021 were selected as the observation objects, and then divided into a control group and an observation group using the random number table method, with 49 cases in each group. The control group received routine admission guidance and active respiratory circulation training, while the observation group was supplemented with external diaphragm pacemaker on the basis of the control group. The intervention effect was evaluated by blood gas indicators, pulmonary function indicators, diaphragm function indicators, sputum comfort degree, and activity tolerance indicators before and after intervention. Results: Before intervention, there were no significant differences in blood gas analysis indicators, pulmonary function indicators, diaphragm function indicators, sputum comfort degree, and activity tolerance indicators between the two groups (P > 0.05). After intervention, the improvement degree of the above indicators in the observation group was higher than that in the control group (P < 0.05). Conclusions: The application of external diaphragm pacemaker combined with active respiratory circulation technology in pulmonary rehabilitation of perioperative lung cancer patients is significant, which can effectively improve the pulmonary function, blood gas function, and diaphragm function of lung cancer patients after surgery, and improve the activities of daily living and quality of life of patients.

Associations of self-reported and device-assessed physical activity with fatigue,quality of life,and sleep quality in adults living with and beyond cancer

Background Greater physical activity is associated with improved outcomes in people living with and beyond cancer.However,most studies in exercise oncology use self-reported measures of physical activity.Few have explored agreement between self-reported and device-based measures of physical activity in people living with and beyond cancer.This study aimed to describe physical activity in adults affected by cancer across self-reported and device-assessed activity,to explore levels of agreement between these measures in terms of their utility for categorizing participants as meeting/not meeting physical activity guidelines,and to explore whether meeting guidelines is associated with fatigue,quality of life,and sleep quality.Methods A total of 1348 adults living with and beyond cancer from the Advancing Survivorship Cancer Outcomes Trial completed a survey assessing fatigue,quality of life,sleep quality,and physical activity.The Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to calculate a Leisure Score Index(LSI)and an estimate of moderate-to-vigorous physical activity(MVPA).Average daily steps and weekly aerobic steps were derived from pedometers worn by participants.Results The percentage of individuals meeting physical activity guidelines was 44.3%using LSI,49.5%using MVPA,10.8%using average daily steps,and 28.5%using weekly aerobic steps.Agreement(Cohen'sκ)between self-reported and pedometer measures ranged from 0.13(LSI vs.average daily steps)to 0.60(LSI vs.MVPA).After adjusting for sociodemographic and health-related covariates,meeting activity guidelines using all measures was associated with not experiencing severe fatigue(odds ratios(ORs):1.43–1.97).Meeting guidelines using MVPA was associated with no quality-of-life issues(OR=1.53).Meeting guidelines using both self-reported measures were associated with good sleep quality(ORs:1.33–1.40).Conclusion Less than half of all adults affected by cancer are meeting physical activity guidelines,regardless of measure.Meeting guidelines is associated with lower fatigue across all measures.Associations with quality of life and sleep differ depending on measure.Future research should consider the impact of physical activity measure on findings,and where possible,use multiple measures.

Surface activity of cancer cells:The fusion of two cell aggregates

A key feature that distinguishes cancer cells from all other cells is their capability to spread throughout the body.Although how cancer cells collectively migrate by following molecular rules which influence the state of cell-cell adhesion contacts has been comprehensively formulated,the impact of physical interactions on cell spreading remains less understood.Cumulative effects of physical interactions exist as the interplay between various physical parameters such as(1)tissue surface tension,(2)viscoelasticity caused by collective cell migration,and(3)solid stress accumulated in the cell aggregate core region.This review aims to point out the role of these physical parameters in cancer cell spreading by considering and comparing the rearrangement of various mono-cultured cancer and epithelial model systems such as the fusion of two cell aggregates.While epithelial cells undergo volumetric cell rearrangement driven by the tissue surface tension,which directs cell movement from the surface to the core region of two-aggregate systems,cancer cells rather perform surface cell rearrangement.Cancer cells migrate toward the surface of the two-aggregate system driven by the solid stress while the surface tension is significantly reduced.The solid stress,accumulated in the core region of the two-aggregate system,is capable of suppressing the movement of epithelial cells that can undergo the jamming state transition;however,this stress enhances the movement of cancer cells.We have focused here on the multi-scale rheological modeling approaches that aimed at reproducing and understanding these biological systems.

Synthesis of Anti-Pancreatic Cancer Natural Product Majusculamide D and Analogues Reveals a Preliminary Structure-Activity Relationships

The total synthesis of majusculamide D(1)was achieved from commercially available materials.In addition,we synthesized eight analogues including three stereoisomers of majusculamide D that differ in the fatty acid chain.Six analogues including a simplified analogue 29 exhibited significant nanomolar-level IC50 values against Panc-1 cells in MTT assays.A preliminary SAR analysis indicated that the hydroxyl group at C10 and C2−C3 unsaturated double bond of majusculamide D were essential in maintaining the high activity against Panc-1 cells and the orientation of C40-Me and C42-Me groups was tolerable.

Lung Cancer Risk Attributable to Active Smoking in China:A Systematic Review and Meta-Analysis

Objective No consensus exists on the relative risk(RR)of lung cancer(LC)attributable to active smoking in China.This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population.Methods A systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China.Primary articles on LC providing risk estimates with their 95%confidence intervals(CIs)for“ever”“former”or“current”smokers from China were selected.Meta-analysis was used to estimate the pooled RR of active smoking.Results Forty-four unique studies were included.Compared with that of nonsmokers,the pooled RR(95%CI)for“ever”“former”and“current”smokers were 3.26(2.79–3.82),2.95(1.71–5.08),and 5.16(2.58–10.34)among men,3.18(2.78–3.63),2.70(2.08–3.51),and 4.27(3.61–5.06)among women,and2.71(2.12–3.46),2.66(2.45–2.88),and 4.21(3.25–5.45)in both sexes combined,respectively.Conclusion The RR of LC has remained relatively stable(range,2–6)over the past four decades in China.Early quitting of smoking could reduce the RR to some extent;however,completely refraining from smoking is the best way to avoid its adverse effects.

Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal/recto sigmoid cancer

AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinicopathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (＞40%) and low (≤40%) expression. Areas of extensive proliferation (＞50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P＜0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) andpresence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.

Anti Cervix Cancer Activity of Co-immobilized Tumor Necrosis Factor-α and Interferon-γ

Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.

Berberine displays antitumor activity in esophageal cancer cells in vitro

To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms. METHODS Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting. RESULTS Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 mu mol/L berberine for 48 h, the number of cells in G2/M phase (25.94% +/- 5.01%) was significantly higher than that in the control group (9.77% +/- 1.28%, P < 0.01), and berberine treatment resulted in p21 upregulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner. CONCLUSION Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients.

Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation

AIM： To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology （PLC） examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression.METHODS： Telomeric repeated amplification protocol （TRAP）-enzyme-linked immunosorbent assay （ELISA） was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen （PCNA） in gastric carcinoma was immunohistochemically examined.RESULTS： The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% （25/60）, and 25.0% （15/60）, respectively. The positive rate of telomerase activity was significantly higher than that Qf PLC in the group of pT, （15/16 vs 9/16, P 〈 0.05）, P1-3 （13/13 vs 9/13, P 〈 0.05） and diffuse type （22/42 vs 13/42, P 〈 0.05）. The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index （PI）, （55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ±10.18 vs 29.15 ±8.31, and 49.82 ± 6.74 vs 24.65 ±7.33, respectively, P 〈 0.05）.CONCLUSION： The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

Effect and feasibility of wearable physical activity trackers and pedometers for increasing physical activity and improving health outcomes in cancer survivors:A systematic review and meta-analysis

Purpose:This systematic review and meta-analysis aimed to evaluate the effect of wearable devices for improving physical activity and healthrelated outcomes in cancer survivors.Methods:CINAHL,Cochrane,Ebscohost,MEDLINE,Pubmed,ProQuest Health and Medical Complete,ProQuest Nursing and Allied Health Source,ScienceDirect,and SPORTDiscus databases were searched for randomized controlled trials published before September 1,2020,that evaluated interventions involving wearable devices in cancer survivors.Standardized mean differences(SMDs)were calculated to assess effects on physical activity and health-related outcomes.Subgroup analyses were conducted to assess whether the effects differed by interventions and cancer characteristics.Risk of bias was assessed using the Cochrane risk of bias tool.Results:Thirty-five trials were included(breast cancer,n=15,43%).Intervention durations ranged between 4 weeks and 1 year.Most trials(n=25,71%)involved pedometer-based physical activity interventions.Seven(20%)involved Fitbit-based interventions,and 3(9%)involved other wearable physical activity trackers(e.g.,Polar,Garmin).Compared to usual care,wearable devices had moderate-to-large effects(SMD range 0.54-0.87,p<0.001)on moderate-intensity physical activity,moderate-to-vigorous-intensity physical activity,total physical activity,and daily steps.Compared to usual care,those in the intervention had higher quality of life,aerobic fitness,physical function,and reduced fatigue(SMD range=0.18-0.66,all p<0.05).Conclusion:Wearable physical activity trackers and pedometers are effective tools that increase physical activity and improve health-related outcomes in individuals with cancer.Identifying how these devices can be implemented for longer-term use with other intervention components remains an area for future research.

Association between physical activity and digestive-system cancer: An updated systematic review and meta-analysis

Background:Physical activity(PA)may have an impact on digestive-system cancer(DSC)by improving insulin sensitivity and anticancer immune function and by reducing the exposure of the digestive tract to carcinogens by stimulating gastrointestinal motility,thus reducing transit time.The current study aimed to determine the effect of PA on different types of DSC via a systematic review and meta-analysis.Methods:In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,we searched for relevant studies in PubMed,Embase,Web of Science,Cochrane Library,and China National Knowledge Infrastructure.Using a random effects model,the relationship between PA and different types of DSC was analyzed.Results:The data used for meta-analysis were derived from 161 risk estimates in 47 studies involving 5,797,768 participants and 55,162 cases.We assessed the pooled associations between high vs.low PA levels and the risk of DSC(risk ratio(RR)=0.82,95%confidence interval(95%CI):0.79-0.85),colon cancer(RR=0.81,95%CI:0.76-0.87),rectal cancer(RR=0.88,95%CI:0.80-0.98),colorectal cancer(RR=0.77,95%CI:0.69-0.85),gallbladder cancer(RR=0.79,95%CI:0.64-0.98),gastric cancer(RR=0.83,95%CI:0.76-0.91),liver cancer(RR=0.73,0.60-0.89),oropharyngeal cancer(RR=0.79,95%CI:0.72-0.87),and pancreatic cancer(RR=0.85,95%CI:0.78-0.93).The findings were comparable between case-control studies(RR=0.73,95%CI:0.68-0.78)and prospective cohort studies(RR=0.88,95%CI:0.80-0.91).The meta-analysis of 9 studies reporting low,moderate,and high PA levels,with 17 risk estimates,showed that compared to low PA,moderate PA may also reduce the risk of DSC(RR=0.89,95%CI:0.80-1.00),while compared to moderate PA,high PA seemed to slightly increase the risk of DSC,although the results were not statistically significant(RR=1.11,95%CI:0.94-1.32).In addition,limited evidence from 5 studies suggested that meeting the international PA guidelines might not significantly reduce the risk of DSC(RR=0.96,95%CI:0.91-1.02).Conclusion:Compared to previous research,this systematic review has provided more comprehensive information about the inverse relationship between PA and DSC risk.The updated evidence from the current meta-analysis indicates that a moderate-to-high PA level is a common protective factor that can significantly lower the overall risk of DSC.However,the reduction rate for specific cancers may vary.In addition,limited evidence suggests that meeting the international PA guidelines might not significantly reduce the risk of DSC.Thus,future studies must be conducted to determine the optimal dosage,frequency,intensity,and duration of PA required to reduce DSC risk effectively.

Assessment of platelet activation and phagocytic activity in gastric cancer patients

AIM:To assess the activation of platelets and their phagocytic activity in the course of gastric cancer.METHODS:Forty-three gastric cancer patients were recruited to the study.The patients were divided into 3 groups depending on tumor stage.Group E included 6 patients with early gastric cancer;group A 18 patients with locally advanced cancer;and group M-19 with metastatic cancer.The investigations were performed twice,prior to surgery and 12-14 d afterwards.RESULTS:The platelet count and the level of soluble platelet selectin(sP-selectin) were found to increase with the disease progression.The level of sP-selectin was lowest in early cancer and was observed to increase after surgery in all the study patients.Irrespective of tumor stage,a statistically significant decrease was noted in the percentage of phagocytizing platelets and in the phagocytic index in gastric cancer patients as compared to healthy subjects.Despite increasedplatelet count and stimulation of thrombocytopoiesis,the phagocytic functions of blood platelets were markedly impaired.Tumor development seems to impair metabolic processes.CONCLUSION:A decreasing phagocytic activity can promote both inflammatory processes and cancer growth.

Physical activity engagement after breast cancer: Advancing the health of survivors

Background: Physical inactivity is identified as the fourth leading risk factor for global mortality and associated with increased breast cancer diagnosis and risks of recurrence. Objectives: To investigate the level of physical activity engagement after breast cancer in survivors and healthy controls. Design: A descriptive casecontrol study on survivors and matched (ethnic, gender, age) healthy controls was surveyed using a pre-post questionnaire and a 1-minute cancer control media. The socio- and medical demographic data, physical activity status information were obtained from self report questionnaires. Results: Breast cancer survivors (n = 51) were found to participate in low-moderate level of physical activity while healthy controls (n = 45) participated in moderate-vigorous level of physical activity. Healthy adults reported more barriers and excuses but all participants (90% survivors and control) were unaware of the strong inverse relationship between level of physical activity and risks of cancer recurrence. The post test on video showed an increased awareness and intention to re-engagement in physical activity for cancer control (M = 7.1 ± 1.53, p < 0.01). Conclusion: The finding suggests that simple public health message within the Model of cancer survivorship care must be disseminated. The “teachable moments” after a cancer diagnosis should be optimised to promote rehabilitation for physically active lifestyle.

Scoping review: obese elderly women with breast cancer and physical activity/exercise

Objective:Obesity and breast cancer(BC)are diseases of concern,especially within the context of an aging population.This scoping review is aimed at mapping out the literature on the subject of elderly women(EW)with breast cancer,obesity and physical activity/exercise(PAE)to identify gaps in the present extant literature,and to suggest directions for future research.Data sources:A total of four articles were finalized from an initial 2905 articles found via searches on the Annals of Internal Medicine by American College of Physicians(ACP)^(TM),BioMed Central(BMC)^(TM),BMJ Journals^(TM),Journal of the American Medical Association(JAMA)^(TM),PubMed^(TM),SAGE^(TM),ScienceDirect^(TM),SpringerLink(e-journals)^(TM),Taylor and Francis Online^(TM),and Wiley Online Library^(TM) databases.Methods:Recognized structural frameworks for scoping reviews were utilized to guide the methodology and technical aspects of this paper.Data extraction was conducted via a charting table.Results:Research gaps identified include a paucity in research on the subject of obesity and breast cancer among elderly women;there is a limitation of the types of methodologies used in the research on this subject indicating vast opportunities for future studies using different methodologies;lack of use of the alternative types of physical activity and exercise such as Tai Chi,Qigong and Yoga;lack of focus on the older elderly population;and areas of social support from family and friends for obese elderly with breast cancer to engage in physical activity and exercise.Conclusion:Future research would address the urgent need within academia to address the research gap of PAE and EWBC.Such research should use a diverse range of both quantitative and qualitative research methodologies,while including eastern exercise regimens such as Tai Chi,Qigong and Yoga as a means of studying PAE among EWBC.Additionally,future research may focus on the“old elderly”as a demographic group of study as well as how social support may encourage PAE among EWBC.

Content determination of benzyl glucosinolate and anti—cancer activity of its hydrolysis product in Carica papaya L.

Objective:To determine the content of benzyl glueosinolate（BG） in the pulp and the seed and investigate the anti-cuncer activity of its hydrolysis product in Curica papaya L.Methods: Determination of BG was performed on an Hypersil BDS C18 column at the wavelength of 214 nm with 0.1%trifluoroacelic acid（TFA） aqueous solution（A） and 0.1%TFA acelonilrile（B） as the mobile phase.In vitro activity test was adopted with cidtured human lung cancer H69 cell in vitro to investigate the inhibition rate of cell proliferation of benzyl isothiocyanale（BITC） againsl H69 cell.Results:The pulp has more BG before the maturation of papaya and it nearly disappeared after papaya matured,while the seed contains BG at every stage.Activity test demonstrated that the a higher concentration of BITC would have betler inhibition rate of cell proliferation on 1169 cell,and the IC50 was 6.5μmol/L.Conclusions:BG also can be produced in the pulp of papaya and it will be stored in the seed after the fruit has been matured.The hydrolysis product of BG has certain cancer-prevention anti-cancer activities for human.

Chemical Characterization and Cytotoxic Activity of Antarctic Macroalgae Extracts against Colorectal Cancer

Background/Aim: Antarctic seaweeds are considered a promising source of compounds with anticancer activity. Colorectal cancer (CRC) is one of the most incident cancers with high mortality rates worldwide. This work aimed to characterize chemically extracts of the Antarctic macroalgae Iridaea cordata, Cystosphaera jacquinotii and Desmarestia anceps and to evaluate the cytotoxic effects against human colon cancer HCT 116 cell line. Materials and Methods: The extracts were obtained by depletion using an ultrasound probe and were identified by High-Performance Liquid Chromatography (HPLC) and Gas Chromatography coupled with Mass Spectrometry (GC-MS). Cell viability was determined by MTT assay. Results: Hexanic and chloroform extracts of the I. cordata and the hexanic, chloroform and methanolic extracts of D. anceps were able to inhibit growth of colorectal cancer cells in the three different incubation times (24, 48 and 72 h). Through GC analysis, 01 compounds were identified in the hexane extract and 02 compounds in the chloroform extract of the algae I. cordata. The hexane extract of D. anceps macroalgae presented 5 compounds, chloroform extract 10 and methanolic extract 3 respectively, with special highlight to fucosterol. Carotenoid analysis by HPLC identified β-carotene in all species, while zeaxanthin was present in the spectrum of I. cordata and C. jacquinotii. Fucoxanthin and violaxanthin were confirmed in the brown seaweeds C. jacquinotii and D. anceps. Conclusion: Extracts of macroalgae I. Cordata and D. anceps may be a source of therapeutic agents against CRC.

Anticancer activity of Salvia officinalis essential oil and its principal constituents against hormone-dependent tumour cells

Objective: To investigate the in vitro antiproliferative action of essential oil from Salvia officinalis L.(S. officinalis) grown in Sicily(Italy), and its main components on hormone-dependent cancer cell lines. Methods: S. officinalis essential oil was prepared by hydrodistillation. The actions of the S. officinalis essential oil and its three principal components(毩-thujone, 1,8-cineole and camphor) were evaluated in LNCaP cells(prostate carcinoma), MCF7 cells(breast carcinoma) and He La cells(cervical carcinoma) at various dosages and diverse time points. Cell viability and proliferation were estimated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results: S. officinalis essential oil at doses of 100 μg/m L and 200 μg/m L induced a significant reduction of cell viability in MCF7, LNCa P and He La cell lines after a 48-hour incubation. The same cell lines also showed decreased cell viability when they were treated with a mixture of three major components of the essential oil, at doses of 100 μg/mL and 200 μg/mL, after a 48-hour incubation. Conclusions: These preliminary results could shed light on the formulation of new therapeutic agents with antiproliferative activity. Thus supplementary investigations are fundamental to examine the molecular mechanisms of the anticancer effects of this species of Salvia in cancer cells and to achieve confirmation of its in vivo anticancer activity.

LA-D-B1,a novel Abemaciclib derivative,exerts anti-breast cancer effects through CDK4/6

Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis,and has a single treatment method.As one of the CDK4/6 inhibitors,abemaciclib can effectively inhibit the growth of breast tumors.In this study,we synthesized LA-D-B1,a derivative of Abemaciclib,and investigated its anti-tumor effects in breast cancer.Methods:Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Cell cloning and migration abilities were determined by colony formation assay and wound healing assay.Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay.The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting,which quantified the levels of proteins associated with the cyclin-dependent kinase(CDK)4/6-cyclin D-Rb-E2F pathway.The in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane(CAM)model.Results:The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation,induced apoptosis,and caused cell cycle arrest.Furthermore,LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway,including CDK4,CDK6 and E2F1.The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model.Conclusion:In this study,LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer.These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.