A phase II trial of netupitant/palonosetron for prevention of chemotherapy-induced nausea/vomiting in patients receiving BEAM prior to hematopoietic cell transplantation.

Objective: The purpose of this study was to investigate the efficacy and safety of netupitant/palonosetron (NEPA) for the prevention of chemotherapy-induced nausea and vomiting (CINV) for hematopoietic cell transplantation (HCT) patients receiving BEAM therapy. Study Design: This phase II, prospective, intention-to-treat, single-center, single-arm study involved 43 adult patients who received NEPA and dexamethasone for the prevention of CINV due to BEAM conditioning chemotherapy. An interim analysis, performed after 13 patients, determined utility versus futility, and supported continuation to full enrollment. Descriptive statistics were used to report complete response (CR), complete protection, incidence of emesis, and administration of rescue agents. A Kaplan-Meier curve depicted time to first emesis and first rescue medication. Patients self-reported levels of daily nausea descriptively via a CINV Questionnaire. Results: By study end, 13 of 43 patients achieved a CR with an average of 10.6 emesis-free days (SD 0.95) over the 11-day observation period, with no emetic events in any patient during the acute/chemotherapy phase. Nausea was well-controlled throughout the acute therapy phase (Day 1-6) and increased during the delayed phase (Day 7-11) with a peak mean level of 2.79/10 at Day 10. Aside from lower grade (≤2), headaches, constipation, and diarrhea were the most widely reported adverse effects. Conclusion: The combination of NEPA and dexamethasone is safe and effective for the prevention of CINV in patients receiving BEAM conditioning therapy prior to HCT. The regimen demonstrated greater effectiveness in the acute phase versus the delayed phase, with low levels of nausea throughout the study period and complete emesis prevention during chemotherapy.

Patients' experiences following local-regional recurrence of thyroid cancer: a qualitative study.

BACKGROUND AND OBJECTIVE: The psychosocial impact of local-regional thyroid cancer recurrence is not known. The aim of this study was to explore thyroid cancer patients' experiences relating to diagnosis and treatment of local-regional disease recurrence. METHODS: We conducted 15 semi-structured interviews with survivors of differentiated thyroid cancer who underwent neck reoperation for recurrent disease. Participants were recruited from the clinical practices of thyroid surgeons and endocrinologists at University Health Network and Mount Sinai Hospitals in Toronto, Ontario. Participant interviews were audio-recorded, transcribed verbatim, and analyzed using qualitative methods. Saturation of themes was achieved. RESULTS: Local-regional recurrence of thyroid cancer was associated with significant psychological distress. Confidence in healthcare providers as well as psychosocial support from family or social relations, were helpful in coping with disease recurrence. After recovery from treatment, post-traumatic growth was reported. However, questions and worry about the risk for future recurrence lingered at follow-up. CONCLUSIONS: Local-regional recurrence of thyroid cancer has a significant psychosocial impact on patients, and support needs are heightened throughout the experience. Healthcare providers should strive to ensure that medical information and psychosocial needs of such patients are met, throughout the treatment experience, as well as at follow-up.

Heterotrimeric G-protein complex and G-protein-coupled receptor from a legume (Pisum sativum): role in salinity and heat stress and cross-talk with phospholipase C.

Heterotrimeric G-proteins transduce signals from activated G-protein-coupled receptors (GPCR) to appropriate downstream effectors and thereby play an important role in signaling. A role of G-proteins in salinity and heat stress tolerance has not heretofore been described. We report isolation of cDNAs of two isoforms of Galpha (Galpha1, 1152 bp; Galpha2, 1152 bp), one Gbeta (1134 bp), two isoforms of Ggamma (Ggamma1, 345 bp; Ggamma2, 303 bp) and a GPCR (1008 bp) from Pisum sativum, and purification of all the encoded recombinant proteins (Galpha, 44 kDa; Gbeta, 41 kDa; Ggamma, 14 kDa; GPCR, 35 kDa). The transcript levels of Galpha and Gbeta were upregulated following NaCl, heat and H(2)O(2) treatments. Protein-protein interaction studies using an in vitro yeast two-hybrid system and in planta co-immunoprecipitation showed that the Galpha subunit interacted with the pea Gbeta subunit and pea phospholipase C (PLCdelta) at the calcium-binding domain (fn1). The GTPase activity of the Galpha subunit increased after interaction with PLCdelta. The GPCR protein interacted with all the subunits of G-proteins and with itself. Transgenic tobacco plants (T(0) and T(1)) constitutively over-expressing Galpha showed tolerance to salinity and heat, while Gbeta-over-expressing plants showed only heat tolerance, as tested by leaf disk senescence assay and germination/growth of T(1) seeds/seedlings. These findings provide direct evidence for a novel role of Galpha and Gbeta subunits in abiotic stress tolerance and possible cross-talk between PLC- and G-protein-mediated signaling pathways.