Effectiveness of zolpidem and sleep hygiene counseling in the treatment of insomnia in solid tumor patients.

OBJECTIVE: To study the effectiveness of zolpidem and sleep hygiene counseling in managing insomnia in solid tumor patients. METHODS: Cancer patients with a Pittsburgh Sleep Quality Index score ≥ 5 were grouped into two. Both groups received treatment for insomnia in the form of either zolpidem 5 mg for 7 days or sleep hygiene counseling. RESULT: At baseline, zolpidem and counseling group had a mean Pittsburgh Sleep Quality Index score of 14.82 ± 2.61 and 11.67 ± 3.32, respectively. The difference in mean Pittsburgh Sleep Quality Index score was found to be 4.03 in patients using zolpidem and 1.5 in counseled patients (p = 0.003). The components of Pittsburgh Sleep Quality Index namely difficulty falling asleep within 30 min (sleep latency), overall sleep quality, trouble staying awake during daytime and trouble staying motivated to get things done showed statistically significant improvement after treatment with zolpidem. Following sleep hygiene counseling, the proportion of patients with sleep latency > 30 min reduced considerably. Waking up to use the bathroom was the most common problem reported by approximately 94% patients in both groups before treatment which remained the most prevalent problem even after treatment. Night or early morning awakenings seemed to decrease significantly in patients taking zolpidem (p = 0.039) while it did not show any improvement with counseling. Counseling seemed to get patients to sleep within 30 min. CONCLUSION: Patients on zolpidem showed a reduction in their Pittsburgh Sleep Quality Index scores thereby suggesting it as a treatment for insomnia in solid tumor patients. Sleep hygiene counseling, though not as effective as zolpidem, made a slight difference in the overall sleep.

Predictive models for designing potent tyrosine kinase inhibitors in chronic myeloid leukemia for understanding its molecular mechanism of resistance by molecular docking and dynamics simulations.

BCR-ABL fusion protein drives chronic myeloid leukemia (CML) which constitutively activates tyrosine kinase involved in the initiation and maintenance of CML phenotype. Ponatinib, an oral drug, was discovered as an efficient BCR-ABL inhibitor by addressing imatinib drug resistance arising due to the point mutations at its active sites. In this study, 44 BCR-ABL kinase inhibitors, which are derivatives of ponatinib, were used to develop a robust two-dimensional quantitative structure-activity relationship (2D-QSAR) and 3D-Pharmacophore models by dividing dataset into 32 training sets and 12 test set molecules. 2D-QSAR model was developed using Genetic Function Approximation (GFA) algorithm consisting of four types of information-rich molecular descriptors, electrotopological (ES_Count_aasN and ES_Sum_aaaC), electronic (Dipole_X), spatial (PMI_Y) and thermodynamic (LogD), primarily contributing to BCR-ABL kinase inhibitory activity. For the best 2D-QSAR model, the statistics were R2 = 0.8707, R2pred = 0.8142 and N = 32 for the training set molecules. Phase module of Schrödinger suit was employed for 3D-Pharmacophore model development showing five different pharmacophoric features - ADHHPRR with good R2 of 0.9629, F of 175.3, Q2 of 0.645 and root-mean-square error (RMSE) of 0.214 that are essential for an effective BCR-ABL kinase inhibition. These two models were further validated by cross-validation, test set predictions, enrichment factor calculations and predictions based on the external dataset. The molecular mechanism of resistance arising due to gate keeper mutation T315I of ABL kinase in complex with its inhibitors was also studied using molecular docking and molecular dynamics simulations. Our developed models predicted key chemical features for designing potent inhibitors against BCR-ABL kinase activity and its resistance mechanism to CML disease therapy. Communicated by Ramaswamy H. Sarma.

Crizotinib, an Effective Agent in ROS1-Rearranged Adenocarcinoma of Lungs: A Case Report.

INTRODUCTION: ROS1 rearrangement has recently emerged as a new molecular subtype in non-small-cell lung cancer (NSCLC) and is predominantly found in lung adenocarcinoma compared with other oncogenes such as EGFR, KRAS, or ALK. It has been identified in only 1% to 2% of NSCLC cases. CASE REPORT: We report a case of 52-year-old man (nonsmoker) with a medical history of allergic rhinitis and bronchial asthma. Histopathologic examination of bronchoscopic-guided biopsy showed adenocarcinoma histology on September 2015. After 2 months, he developed left-sided pneumonia for which he was treated with multiple intravenous antibiotics. In the meantime, fiberoptic bronchoscopy was done which revealed purulent secretion from right upper lobe and narrowed opening of right middle lobe. His cancer symptoms got worsened and bronchial biopsy showed EGFR mutation negative. For further diagnosis, fluorescent in situ hybridization test was done which showed ROS1 mutation positive. By then, the patient was started with crizotinib 250 mg twice daily for ROS1 mutation in July 2016. Later, patient appears to benefit from treatment with crizotinib. X-ray report and positron emission tomographic-computed tomographic scan revealed that the patient was overall better with clear chest and well tolerated with the therapy. Crizotinib was approved on March 11, 2016 by Food and Drug Administration for the treatment of patients with ROS1-positive NSCLC. CONCLUSIONS: In this report, crizotinib showed marked antitumor activity in patients with advanced ROS1 rearrangement, a third molecular subgroup of NSCLC.

The significance of the site of origin in primary peritoneal carcinosarcoma: case report and literature review.

Primary peritoneal carcinomas are rare, highly aggressive malignant neoplasms containing both sarcomatous and carcinomatous elements. Surgical debulking is the mainstay of treatment for primary peritoneal carcinomas. Systemic chemotherapy is advised in all cases because of the early spreading of these tumours. We report on a case of primary peritoneal carcinosarcoma occurring in a 22-year-old woman.