STUDY DESIGN: Observational cross-sectional study.
SETTING: Tertiary care center.
PATIENTS: Adult survivors of cancer who had completed cisplatin treatment.
MAIN OUTCOME MEASURES: Patient-reported balance symptoms were evaluated by a semistructured clinical interview. Patients underwent bedside clinical tests including Dynamic Visual Acuity test, Modified Clinical Testing of Sensory Interaction and Balance (CTSIB-m), and vibration sense testing to detect peripheral neuropathy. The video Head Impulse Test (vHIT) of all semicircular canals was performed.
RESULTS: Eleven of 65 patients (17%) reported some balance symptoms after cisplatin therapy, including vertigo, dizziness, unsteadiness, and falls. Vertigo was the most common balance symptom, reported by six patients (9.2%), and the clinical histories of these patients were consistent with benign paroxysmal positional vertigo. Three patients (5%) had abnormal results of the CTSIB-m test, and they were the same patients who reported falls. There was a significant association of peripheral neuropathy detected by vibration test and balance symptoms. All patients had normal vHIT results in all semicircular canals.
CONCLUSIONS: Balance symptoms after cisplatin treatment occurred in 17% of adult cancer survivors. Patients with peripheral neuropathy were more likely to have balance symptoms. The CTSIB-m test is a useful bedside physical examination to identify patients with a high risk of fall. Though there was no vestibular dysfunction detected by the vHIT in cancer survivors after cisplatin therapy, benign paroxysmal positional vertigo was relatively prevalent in this group of patients.
AIM OF THE STUDY: To assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines.
MATERIALS AND METHODS: The cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays.
RESULTS: In our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days.
CONCLUSION: Our data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.