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1.  Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence 
British Journal of Cancer  2011;105(6):796-806.
We reported that Notch-1, a potent breast oncogene, is activated in response to trastuzumab and contributes to trastuzumab resistance in vitro. We sought to determine the preclinical benefit of combining a Notch inhibitor (γ-secretase inhibitor (GSI)) and trastuzumab in both trastuzumab-sensitive and trastuzumab-resistant, ErbB-2-positive, BT474 breast tumours in vivo. We also studied if the combination therapy of lapatinib plus GSI can induce tumour regression of ErbB-2-positive breast cancer.
We generated orthotopic breast tumour xenografts from trastuzumab- or lapatinib-sensitive and trastuzumab-resistant BT474 cells. We investigated the antitumour activities of two distinct GSIs, LY 411 575 and MRK-003, in vivo.
Our findings showed that combining trastuzumab plus a GSI completely prevented (MRK-003 GSI) or significantly reduced (LY 411 575 GSI) breast tumour recurrence post-trastuzumab treatment in sensitive tumours. Moreover, combining lapatinib plus MRK-003 GSI showed significant reduction of tumour growth. Furthermore, a GSI partially reversed trastuzumab resistance in resistant tumours.
Our data suggest that a combined inhibition of Notch and ErbB-2 signalling pathways could decrease recurrence rates for ErbB-2-positive breast tumours and may be beneficial in the treatment of recurrent trastuzumab-resistant disease.
PMCID: PMC3171020  PMID: 21847123
ErbB-2; trastuzumab; Notch-1; GSI; recurrence; resistance
2.  Evaluation of immunomodulatory effect of Ranahamsa Rasayanaya – A Sri Lankan classical rasayana drug, on experimental animals 
Ayu  2010;31(4):495-499.
Immunity plays a key role in maintaining the health of an individual. Therefore, the rational modulation of the immunity through psycho-neuro-endocrine-immune (PNI) axis is useful for the prevention as well as for the curing of the diseases. As immunomodulation is a parameter for evaluation of the rasayana effect of a drug, the same has been studied to assess the rasayana effect of Ranahamsa Rasayanaya (RR). Experimental models such as antibody formation against sheep red blood cells (SRBC) and cell mediated immunity (CMI) have been carried out befitting on Wistar strain albino rats to determine the immunomodulatory effect plus rasayana effect of RR. Statistically significant increase in body weight, nonsignificant increase in antibody formation against SRBC, highly significant decrease in CMI were observed in the treatment groups, when compared to the standard control group. These results show the probable immunomodulatory and anabolic activities of the test drug. Outcome of these studies validate the strong rasayana effect of the test drug claimed by the traditional practitioners of Sri Lanka.
PMCID: PMC3202263  PMID: 22048546
Ranahamsa Rasayanaya; immunomodulation; Sheep RBC; cell mediated immunity; psychoneuroimmunology; anabolic activity
3.  A short-term intervention trial on HIV positive patients using a Sri Lankan classical rasayana drug – Ranahamsa Rasayanaya 
Ayu  2010;31(2):197-204.
Rational use of Rasayana therapy, in the management of HIV infected individuals, could potentially stabilize the destructive control mechanisms, by modulating the psycho-neuro-endocrine-immune axis. The objective of the present study has been to determine the short-term effects of Ranahamsa Rasayanaya (RR) in HIV infected patients. A total of 27 patients with documented HIV infection were randomly assigned to two groups, Group A – 5 g of RR twice daily with cow's milk and sugar. Group B – Only routine modern therapy was continued, if any they were taking, including highly active anti-retroviral therapy (HAART). Absolute CD4+ T-cell and total lymphocyte counts were measured in these patients, registered under Group A. Only 21 participants completed the study protocol (In Group A, 15 patients and in Group B, 6 patients). Initial mean CD4+ T-cell count was 304.50 ± 43.36 cells/microliter, which increased to 430.44 ± 66.01 cells/microliter by 41.36% (P<0.05), measured among 9 patients out of 15, who received RR in Group A. The RR seemed to be a safer adjuvant in people with HIV infection with respect to absolute CD4+ T-cell count over a 90 days treatment.
PMCID: PMC3215364  PMID: 22131710
CD4+ T-cells; HIV/AIDS; psycho-neuro-endocrine-immune modulation; Rasayana therapy; Ranahamsa rasayanaya.
4.  Evaluation of adaptogenic and anti-stress effects of Ranahamsa Rasayanaya-A Sri Lankan classical Rasayana drug on experimental animals 
Ayu  2010;31(1):88-92.
Various types of stress not only harm the mental function, but also cause diseases by weakening body defenses. Rasayana therapy has an advantage over the conventional Kayachikitsa treatment in such conditions, as it is capable of counteracting the stress, promote the adaptogenic abilities of the body, enhance mental endurance, etc. These are the some of parameters for evaluation the rasayana effect of a drug, therefore the same have been studied to assess the rasayana effect of Ranahamsa Rasayanaya (RR). Experimental models such as forced swimming induced hypothermia and stress induced gastric ulcer formation have been carried out befitting on Charles Foster strain albino rats to determine the rasayana effect of RR. Statistically highly significant decrease in forced swimming induced hypothermia and non-significant decrease in gastric ulcer formation were observed in the treatment groups, when compared to the stress control group. These results show the probable adaptogenic and anti-stress activities of the test drug. The study results support the claims made by the Sri Lankan traditional practitioners that, the test drug is a potent rasayana formulation.
PMCID: PMC3215329  PMID: 22131691
Ranahamsa Rasayanaya; Rasayana therapy; hypothermia; gastro-cytoprotective; adaptogenic; anti-stress activities; traditional practitioners
5.  Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial 
Lancet  2005;366(9488):818-824.
Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer.
420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat.
Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity.
Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.
PMCID: PMC1627210  PMID: 16139656
6.  Near fatal gas embolism during laparoscopic cholecystectomy. 
Laparoscopic cholecystectomy has been greeted with enthusiasm by surgeons and patients alike. However, with the passage of time reports of complications related to this new approach are being published. We report an unusual complication of gas embolism in laparoscopic cholecystectomy. A high index of suspicion along with vigilant intraoperative monitoring will help in the early diagnosis and reduction of morbidity associated with gas embolism.
PMCID: PMC2502512  PMID: 7717649
7.  Lung abscess secondary to xanthogranulomatous pyelonephritis 
Thorax  1990;45(4):297-298.
In a patient with xanthogranulomatous pyelonephritis the initial clinical and radiological picture suggested a diagnosis of lung abscess.
PMCID: PMC473778  PMID: 2356557
10.  Letter from Bombay. An unmitigated tragedy. 
BMJ : British Medical Journal  1988;297(6641):117-119.
PMCID: PMC1833772  PMID: 3408933
11.  Style. 
PMCID: PMC1257526  PMID: 3121126

Results 1-11 (11)