Proproliferative function of adaptor protein GRB10 in prostate carcinoma.

Growth factor receptor-binding protein 10 (GRB10) is a well-known adaptor protein and a recently identified substrate of the mammalian target of rapamycin (mTOR). Depletion of GRB10 increases insulin sensitivity and overexpression suppresses PI3K/Akt signaling. Because the major reason for the limited efficacy of PI3K/Akt-targeted therapies in prostate cancer (PCa) is loss of mTOR-regulated feedback suppression, it is therefore important to assess the functional importance and regulation of GRB10 under these conditions. On the basis of these background observations, we explored the status and functional impact of GRB10 in PCa and found maximum expression in phosphatase and tensin homolog (PTEN)-deficient PCa. In human PCa samples, GRB10 inversely correlated with PTEN and positively correlated with pAKT levels. Knockdown of GRB10 in nontumorigenic PTEN null mouse embryonic fibroblasts and tumorigenic PCa cell lines reduced Akt phosphorylation and selectively activated a panel of receptor tyrosine kinases. Similarly, overexpression of GRB10 in PTEN wild-type PCa cell lines accelerated tumorigenesis and induced Akt phosphorylation. In PTEN wild-type PCa, GRB10 overexpression promoted mediated PTEN interaction and degradation. PI3K (but not mTOR) inhibitors reduced GRB10 expression, suggesting primarily PI3K-driven regulation of GRB10. In summary, our results suggest that GRB10 acts as a major downstream effector of PI3K and has tumor-promoting effects in prostate cancer.-Khan, M. I., Al Johani, A., Hamid, A., Ateeq, B., Manzar, N., Adhami, V. M., Lall, R. K., Rath, S., Sechi, M., Siddiqui, I. A., Choudhry, H., Zamzami, M. A., Havighurst, T. C., Huang, W., Ntambi, J. M., Mukhtar, H. Proproliferatve function of adaptor protein GRB10 in prostate carcinoma.

Comparative study of hamstring and quadriceps strengthening treatments in the management of knee osteoarthritis.

[Purpose] Osteoarthritis (OA) of the knee is the most common form of joint disease. It is one of the major causes of impaired function that reduces quality of life (QOL) worldwide. The purpose of this study was to compare exercise treatments for hamstring and quadriceps strength in the management of knee osteoarthritis. [Subjects and Methods] Forty patients with OA knee, aged 50-65 years were divided into 2 groups. The first group (57.65±4.78 years) received hot packs and performed strengthening exercises for the quadriceps and hamstring, and stretching exercises for the hamstring. The second group (58.15±5.11 years) received hot packs and performed strengthening exercises for only the quadriceps, and stretching exercise for the hamstring. Outcome measures were the WOMAC (Western Ontario and McMaster Universities OA index questionnaire), Visual Analogue Scale (VAS) assessment of pain, the Fifty-Foot Walk Test (FWS), and Handheld dynamometry. [Results] There was a significant difference between the groups. The first group showed a more significant result than the second group. [Conclusion] Strengthening of the hamstrings in addition to strengthening of the quadriceps was shown to be beneficial for improving subjective knee pain, range of motion and decreasing the limitation of functional performance of patients with knee osteoarthritis.

Treatment of knee osteoarthritis in relation to hamstring and quadriceps strength.

[Purpose] To assess the effect of hamstring and quadriceps strengthening exercises on pain intensity, gait velocity, maximum isometric strength, and activities of daily living of patients with knee osteoarthritis (OA). [Subjects and Methods] A total of 20 patients with knee OA, 50 to 65 years of age (57.65 ± 4.78 years), received hot packs, strengthening exercises for the quadriceps and the hamstring muscles and stretching exercises for hamstring muscles. Outcome measures included: the Western Ontario and McMaster Universities OA index questionnaire (WOMAC) scores for assessing health status and health outcomes of knee OA; self-reported pain intensity scores, measured using a visual analogue scale; the 50 ft walk test (a measure of gait velocity and function); and handheld dynamometry (a tool used to measure maximum isometric strength of knee extension and flexion). [Results] There was a significant difference between pre- and post-intervention measures of pain intensity, 50 ft walk times, hamstring strength, and quadriceps strength. Significant differences in WOMAC measures were also observed in the subscales of pain, stiffness and physical function, as well as WOMAC total scores. [Conclusion] Strengthening the hamstring muscles in addition to strengthening the quadriceps muscles proved to be beneficial for perceived knee pain, range of motion, and decreasing the limitation of functional performance of patients with knee OA.

Effect of extracorporeal shock wave therapy on spastic equinus foot in children with unilateral cerebral palsy.

Objectives: This study aims to investigate the effects of radial extracorporeal shock wave therapy on selective motor control, spasticity, gross motor function, and balance in children with unilateral cerebral palsy. Methods: This randomised controlled study recruited 34 children aged 7-9 with spastic unilateral cerebral palsy. They were randomly allocated to either the control or study group. Both groups undertook traditional exercises for 12 weeks. The study group received shock waves (one session/week) on the calf muscle (1500 shocks, frequency of 4 Hz, energy of 0.030 mJ/mm2). All children were evaluated at baseline and after 12 weeks using the Modified Ashworth Scale, a Biodex System 4 isokinetic dynamometer, dimensions D (standing) and E (walking) of the Gross Motor Function Measure - 88, the Trost Selective Motor Control test, and the single leg standing test. Results: Mixed analysis of variance and Mann-Whitney results showed significant improvement in eccentric peak torque, torque threshold angles, gross motor function, selective motor control, and balance in the study group compared with the control group (p < 0.05). Conclusions: Shock wave therapy may be a valuable instrument for reducing spasticity, improving the ability to isolate and control movement, and consequently, improving balance and gross motor function in children with unilateral cerebral palsy.