***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Curcumin ( diferuloylmethane ) , a yellow substance from the root of the plant Curcuma longa Linn . , has been demonstrated to inhibit carcinogenesis of murine skin , stomach , intestine and liver . However , the toxicology , pharmacokinetics and biologically effective dose of curcumin in humans have not been reported . This prospect i ve phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions : 1 ) recently resected urinary bladder cancer ; 2 ) arsenic Bowen 's disease of the skin ; 3 ) uterine cervical intraepithelial neoplasm ( CIN ) ; 4 ) oral leucoplakia ; and 5 ) intestinal metaplasia of the stomach .  Curcumin was taken orally for 3 months . Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament . The starting dose was 500 mg/day . If no toxicity > or = grade II was noted in at least 3 successive patients , the dose was then escalated to another level in the order of 1,000 , 2,000 , 4,000 , 8,000 , and 12,000 mg/day . The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography ( HPLC ) . A total of 25 patients were enrolled in this study . There was no treatment-related toxicity up to 8,000 mg/day . Beyond 8,000 mg/day , the bulky volume of the drug was unacceptable to the patients . The serum concentration of curcumin  usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours . The average peak serum concentrations after taking 4,000 mg , 6,000 mg and 8,000 mg of curcumin were 0.51 + /- 0.11 microM , 0.63 + /- 0.06 microM and 1.77 + /- 1.87 microM , respectively . Urinary excretion of curcumin  was undetectable . One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment . In contrast , histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer , 2 out of 7 patients of oral leucoplakia , 1 out of 6 patients of intestinal metaplasia of the stomach , I out of 4 patients with CIN and 2 out of 6 patients with Bowen 's disease . In conclusion , this study demonstrated that curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3 months . Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer OBJECTIVE Turmeric extract and turmeric oil have shown chemoprotective effect against chemically-induced malignancies in experimental animals . They can reverse precancerous changes in oral submucous fibrosis in humans . The use of turmeric or Curcuma longa Linn as a spice and household remedy has been known to be safe for centuries . In view of the long term administration required for cancer prevention a Phase I clinical trial of turmeric oil ( TO ) was design ed to study the safety and tolerance of TO in volunteers for a period of 3 months . MATERIAL AND METHODS Nine healthy volunteers between 20 and 33 years of age were tested for haemoglobin , blood counts , liver and kidney functions , bleeding and clotting time and serum electrolytes initially and at 1 and 3 months of treatment . They were administered 0.6 ml of TO three times a day for 1 month and 1 ml in 3 divided doses for 2 months . The acute tolerability study on Day 1 was conducted in a Clinical Pharmacology daycare Unit . Blood pressure and pulse were recorded frequently on Day 1 and at 24 , 48 , 72 and 96 hours and fortnightly till 12 weeks . Volunteers were daily supervised for TO intake as well as for any side effects throughout the study period . RESULTS Nine volunteers were enrolled for the study . One discontinued on 3rd day for allergic skin rashes which , on discontinuation of TO , gradually disappeared by two weeks . Another discontinued on 7th day for intercurrent fever requiring antibiotic treatment . Seven volunteers completed the study . There was no effect of TO , in two doses , on pulse and blood pressure and no side effects in acute tolerability study on Day 1 . There was no effect of TO intake on weight , blood pressure , symptoms and signs upto 12 weeks . There was no clinical , haematological , renal or hepatic-toxicity of TO at 1 month and 3 months . Serum lipids did not show significant change except in one volunteer ( reversible ) . CONCLUSIONS In view of the potential for reversing oral submucous fibrosis , a precancerous condition for oral cancer , TO , can be recommended directly for a Phase II trial in patients Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool  for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies 
    Output:
    
These studies demonstrated that curcumin induces cytotoxicity , apoptosis ( via intrinsic pathway ) , and cell cycle arrest in G2 /M phase in HSNCC cell lines .
It also reduces tumor measurements in animal models .
CONCLUSION This systematic review demonstrated that curcumin is effective on HNSCC cell proliferation and survival , reinforcing the currently available evidence that curcumin could be an adjuvant drug in HNSCC treatment