Protocol for a randomised controlled trial of a family strengthening program to prevent unhealthy weight gain among 5 to 11-year-old children from at-risk families : the Strong Families Trial

Background: Obesity is an increasing health concern in Australia among adult and child populations alike and is often associated with other serious comorbidities. While the rise in the prevalence of childhood obesity has plateaued in high-income countries, it continues to increase among children from disadvantaged and culturally diverse backgrounds. The family environment of disadvantaged populations may increase the risk of childhood obesity through unhealthy eating and lifestyle practices. The Strong Families Trial aims to assess the effectiveness of a mixed behavioural and lifestyle intervention for parents and carers of at-risk populations, i.e. families from culturally diverse and disadvantaged backgrounds, in preventing unhealthy weight gain among children aged 5 to 11 years. Methods: Eight hundred families from low socio-economic areas in Greater Western Sydney, NSW, and Melbourne, VIC, will be recruited and randomised into a lifestyle intervention or control group. The intervention comprises 90-minute weekly sessions for 6 weeks (plus two-booster sessions) of an integrated, evidence-based, parenting and lifestyle program that accounts for the influences of family functioning. Primary (anthropometric data) and secondary (family functioning, feeding related parenting, physical activity, consumption of healthy foods, health literacy, family and household costs) outcome measures will be assessed at baseline, immediately following the intervention, and 12 months post-intervention. Discussion: This study will elucidate methods for engaging socially disadvantaged and culturally diverse groups in parenting programs concerned with child weight status. Trial Registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001019190). Registered 16 July 2019

Identifying essential factors for Oncogene-Induced Senescence using a novel cervical cancer cell culture model and high throughput screening approaches

Uterine Cervical Carcinoma (UCC) is the second most common cancer among women in the world and is induced by High risk Human Papillomaviruses (HPV). Cellular senescence is a potent tumor suppression mechanism that protects against cancer by triggering a proliferative arrest normally depending on the p53 and pRb pathways, but it can also promote aging and age-associated diseases. Because UCC cells express the HPV oncogenes E6 and E7 early in cancer progression, inactivating p53 and pRb, senescence is not expected to be functional in UCC. However, we recently found that the expression of oncogenic Ras in E6/E7-expressing primary keratinocytes strongly activated cellular senescence. Hypothesis: p53/pRb independent tumor suppression systems still exist in early UCC cells, and we can use our isogenic normal and HPV-E6/E7 expressing primary keratinocytes model to verify the role of the suspected TGFβ pathway or to identify novel p53/pRb-independent regulators of senescence in UCC. Approaches: I will use normal versus precancerous UCC human keratinocyte cell culture model to: 1. Directly test candidate genes like TGFβ that are potentially responsible for cellular senescence in precancerous UCC cells with inactive p53/pRb. 2. Apply an unbiased genome-wide genetic screen to identify new tumor suppressors that allow cellular senescence bypass in these cells. Conclusion et pertinence: Identified new targets/knowledge could be used to increase the efficacy of primary UCC treatments, lower the risk of recurrence, and to promote our understanding of normal human aging or other age-associated human diseases

Synthesis and anticancer activity evaluation of some hemin and hematoporphyrin derivatives

388-393Sulphamerazine, sulphadiazine, and sulphaguanidine are coupled with hemin to give bis coupled products 1a, 1b and 1c respectively. 3, 4-Diphenyliminothiazoline, sulphamerazine, sulphaacetamide, sulphathiazole and sulphadiazine on coupling with hematoporphyrin give bis coupled products 2a, 2b, 2c, 2d and 2e respectively. Compounds 1a-c and 2a-e have been screened for anticancer activity against a small panel of six cancer cell lines consisting of prostate(DU 145), colon (HT29), melanoma (LOX), breast(MCF7 and MCF7/ADR) and CNS(U251) tumors. Best GI50 (concentration which inhibits the cell growth by 50%) values are shown by 2c, 2.2μM(prostate tumor, cell line DU145); 2c 13.0μM(colon tumor, cell line HT29); 2b, 3.4μM(melanoma tumor, cell line LOX); 2c, 9.7μM(breast tumor, cell line MCF7); 2a, 3.1μM(breast, tumor, cell line MCF7/ADR) and 1c, 3.4μM(CNS tumor, cell line U251) respectively. Out of all the compounds reported here GI50 value shown by 2a i.e.3.1μM against breast, tumor (MCF7/ADR) is quite close to the GI50 value i.e. 1.8μM, of standard drug doxorubicin

Synthesis of biscoupled hemin-thiazoline derivatives and their anticancer activity evaluation

162-167A number of biscoupled hemin-thiazoline derivatives 3a-i have been synthesized and screened in vitro against six human cancer cell lines consisting of lung large (NCIH460), colon (HT29), breast (MCF7 and MCF7/ADR), prostate (DU 145) and CNS (U251) tumors. Compound 3e exhibits good anticancer activity against lung large (NCIH460; GI50 4.3MM), where compound 3g shows good anti cancer activity against colon (HT29; GI50 0.9 μM), breast (MCF7; GI50 0.5μM; MCF7/ADR; GI50 1.8μM), prostate (DU 145; GI50 1.6μM) and CNS (U251; GI50 2.5μM) tumors

Synthesis of sulpha drug acridine derivatives and their evaluation for anti-inflammatory, analgesic and anticancer activity

2659-2666Various sulpha drugs i.e. sulphaacetamide, sulphathiazole, sulphadiazine and sulphamerazine are coupled with 9-chloro-2,4(un)substituted acridines and 9- isothiocyanato-2, 4(un) substituted acridines to give corresponding coupled products 3a-f and 4a-h respectively. The structures of all synthesized compounds have been confirmed by spectroscopic methods. Anti-inflammatory activity evaluation of 3a,b,c and 4a-h was carried out and compounds 4a, 4d, 4g and 4h showed 8,13,22 and 3% activity respectively at 100mg/ kg p.o. Analgesic activity evaluation of 3a,b,c and 4a-h indicated that these compounds possess 25,75,50,25, 50,50, 0.75, 50, 50 and 50% analgesic activity at 100mg/kg p.o. Anticancer activity evaluation of 3a-f and 4a-h against a small panel of seven cancer cell lines consisting of lung (NCIH 460);colon (HT 29): melanoma (LOX); breast (MCF 7 and MCF 7 / ADR); prostate (DU 145) and CNS (U251) tumors was carried out. Best GI50 (concentration which inhibits the cell growth by 50%) values are shown by 4b, 0.4 μM (lung carcinoma, cell line NCIH 460): 4b, 0.3 μM (colon tumor, cell line HT29); 3e, 7.2μm (melanoma tumor, cell line LOX): 4b, 0.7μM (breast tumor, cell line MCF7); 4c, 1.9μM (breast tumor, cell line MCF7/ADR); 4b, 0.8μM (prostate tumor, cell line DU 145) and 4b, 1.4μ M (CNS tumor, cell line U251) respectively. Out of all the compounds reported here GI50 value shown by 4c i.e. 1.9μM against breast tumor (MCF7/ADR) is quite close to the GI50 value i.e.1.2μM of the sta ndard drug doxorubicin. Also it is worthwhile to mention here that compound 4b, has shown good anticancer activity against four tumor cell lines i.e. GI50 value M.</i

Synthesis, hydrolysis over silica column, anticancer, anti-inflammatory and analgesic activity evaluation of some pyridine and pyrazine derivatives

387-399Various 3,4-diaryl-2-iminothiazolines 1a-s have been condensed with 4-cyanopyridine and 2-cyanopyrazine by refluxing in methanol for about 16 hr to give corresponding 3,4-diaryl-2-imino-N-(4'-pyridyliminomethyl)-4-thiazoline (2a-k, n-p) and 3, 4-diaryl-2-imino-N-(2'-pyrazinyliminomethyl)-4-thiazoline (3a-m, q-s) derivatives. In some cases when these pyridyl and pyrazinyl derivatives are purified by column chromatography over silica gel these compounds get hydrolysed to give corresponding 3,4-diaryl-2-imino-N-(4'-carbonylpyridyl)-4-thiazoline (2o,p) and 3,4-diaryl-2-imino-N-(2'-carbonylpyrazinyl)-4-thiazoline (3q-s) derivatives. The structures of all synthesized compounds have been confirmed by spectroscopic methods. Compounds 2a-c,e-h,k,n,p, 3a-i and 3l,m,q are screened for anticancer activity against a small panel of six human cancer cell lines consisting of prostate (DU 145) colon (HT 29) breast (MCF 7) breast (MCF 7/ADR), CNS (U 251) and lung large (NCIH 460) tumors. Best GI50 values are shown by 3f, 11.5 M (prostate tumor, cell line DU 145), 3f, 1.0 M (colon tumor, cell line HT 29), 2n, 6.2M (breast tumor, cell line MCF 7), 2p, 4.8M (breast tumor, cell line MCF 7/ADR), 2p, 6.3M (CNS tumor, cell line U 251) and 3f, 0.9 M (lung large carcinoma, cell line NCIH 460) respectively. Compound 3f has shown good anticancer activity against three cancer cell lines, whereas compounds 2n and 2p against one and two cancer cell lines respectively. Antiinflammatory activity evaluation of 2a-k,n,o,p, 3a-m and 3q,r,s has been carried out and compounds 2a-h, 2j, 2o,p, 3a,b,c,g,m and 3r showed 13, 32.5, 48.8, 6.5, 13.9, 7.0, 4.3, 16.6, 20.0, 17.3, 27.7, 16.2, 18.4, 34.7, 15.6, 24.0 and 4.7% activity, respectively, at 100mg/kg p.o. Analgesic activity, evaluation of 2a-k,n,o,p, 3a-m and 3q,r,s indicates that these compounds possess 50, 25,75, 25, 50, 75, 50, 50, 25, 0.0, 50, 50, 0.0, 75, 50, 25, 25, 25, 75, 0.0, 25, 25, 25, 50, 50, 75, 25, 50, 75 and 50% analgesic activity at 100mg/kg p.o