Ultrastructural observations on foliar glandular trichomes of Stevia rebaudiana

Foliar glandular trichomes of Stevia rebaudiana (Bert.) Bert. were examined by transmission electron microscopy in order to detect changes occurring in their cells in association with the secretory process. In the foliar, 10-celled lipophilic glandular trichome of Stevia rebaudiana (Bert.) Bert., the six secretory cells forming three pairs of head cells are vacuolated, possess large nuclei and are rich in ribosomes, mitochondria, plastids and ER elements. Dictyosomes are relatively frequent in these cells. The plastids, which form starch grains, are leucoplasts in cells of the apical pair and chloroplasts in cells of the two subapical pairs. The basal cells and stalk cells possess some degree of vacuolation and are rich in ribosomes. Also in these cells, the nuclei are relatively large; ER elements, chloroplasts and dictyosomes are present in moderate number, and mitochondria are frequent. Wall ingrowths are found in head cells as well as in the stalk and basal cells. Plasmodesmata, in moderate number, occur more frequently in transverse walls of head cells, as well as in those between cells of the second subapical pair and stalk cells and between the latter and basal cells. Plasmodesmata connect mesophyll cells and basal cells. To form the secretory sheath, the cuticular membrane detaches from the outer walls of the apical secretory cells, along a line that appears to be the pectin layer

Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial

ImportanceLocoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. ObjectiveTo assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. Design, Setting, and ParticipantsThis multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. InterventionsPatients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. Main Outcomes and MeasuresThe primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. ResultsA total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P=.48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). Conclusions and RelevanceThis study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. Trial RegistrationClinicalTrials.gov identifier: NCT01345669Experimentele farmacotherapi