Critical role of H3K27 methylation in cell fate determination of two cell lineages in male gametophyte

During angiosperm male gametogenesis, microspores divide to produce a vegetative cell (VC) and a male germline (MG), each with a distinct cell fate. How the MG cell/VC fate is determined remains largely unknown. Here, we report that H3K27me3 is essential for VC fate commitment and H3K27me3 erasure contributes to the MG cell fate initiation in male gametophyte of Arabidopsis. The VC-targeted H3K27me3 erasure disturbed the VC development and resulted in the VC fate shifting towards a gamete destination, which suggests that MG cells require H3K27me3 erasure for triggering the gamete cell fate. Multi-omics and cytologic analysis confirmed the occurrence of extensive cell identity transition due to H3K27me3 erasure. Therefore, we experimentally confirm that the MG cell/VC fate is epigenetically regulated. The H3K27 methylation plays a critical role in the guidance of MG cell/VC fate determination for pollen fertility in Arabidopsis. Our work also provides new evidences for two previous hypotheses that the germline cell fate is specified by the differential distribution of yet unknown determinant, and VC maintains the microspore's default program, namely the H3K27me3 setting, whereas MG requires reprogramming.

Diagnosis of gastric carcinoma

INTRODUCTION: Gastric cancer is the fourth most commonly diagnosed cancer in the world and the second most common cause of cancer mortality. Diagnosis requires histopathological analysis of tissue obtained by esophagogastroduodenoscopy or cytologic analysis of gastric wiping / flushing. CASE REPORT: Patient aged 55 years presents in a family medical clinic due to dyspeptic problems accompanied by weight loss, weakness and maladaptation present at six months. Physical examination present sensitivity to deep palpation in the epigastrium. Ultrasound abdominal examination neat, laboratory anemia present. The patient is referred for esophagogastroduodenoscopy, which corporally, on a small curve of the stomach, detects a large ulceration of the bottom covered with fibrin and detritus, femoral margins. Bioptate finding reveals the presence of ventriculi mixed adenocarcinoma (tubular adenocarcinoma cum poorly cohesive carcinoma). Computed tomography of the abdomen determines the visible thickening of the stomach in the region of small curvature in the area of dimension 110x 26 mm and a large number of individual lymph glands up to 8 mm in fat with a small curve of the stomach. A total gastrectomy with a lymphadenectomy is done at the request of the oncological consulium. The pathohistological finding after surgery is adenocarcinoma ventriculi gradus III, pT3N1Mx (small curve, part of the anterior and posterior gastric wall infiltrative, engages all layers of the wall, but does not infiltrate serosa, size 7x6 cm, R0L1V0Pn0). A re-examination of the oncology consilium indicates chemotherapy / radiotherapy in hospital conditions and thereafter 5-fluorouracil / leucovorin chemotherapy. CONCLUSION: In the absence of specific symptoms and screening and early detection capabilities, the highest number of gastric cancers is diagnosed at an advanced stage when the prognosis is poor (average survival is 24 months) and treatment options are limited. Identification of new biological / molecular markers in early diagnosis of gastric cancer would allow a better quality of life and longer survival of the diseased.

Yield of biliary stent cytology: Is it time to think lean?

Background and study aims During evaluation of pancreaticobiliary strictures, it is common practice to send biliary stents for cytologic analysis. However, in recent years, complementary tissue acquisition techniques ranging from cholangioscopy to fine-needle biopsy have improved the ability to acquire tissue and diagnose malignancy. Data are limited on the current diagnostic yield and cost effectiveness of biliary stent analysis. Patients and methods We performed a retrospective study of all pancreaticobiliary stents sent for analysis in a tertiary care academic medical center from June 2013 to September 2016. Patient demographics, stent information, and final diagnosis history were collected through chart review. Costs were determined using published reimbursement rates for Medicare. Results Two hundred thirty-one stents from 175 patients were sent for cytologic analysis during the study period. Of the 62 stents obtained from patients ultimately diagnosed with malignancy, only one (1.6 %) had positive cytology for malignant cells, while the others were acellular/non-diagnostic (2/62, 3.2 %), negative (48/62, 77.4 %), or atypical (11/62, 17.7 %). The sensitivity of stent cytology for diagnosis of malignancy was 1.6 % (1/62). No cases were identified in which stent cytology changed clinical management. From a payer perspective, the mean estimated cost for each stent cytologic analysis is greater than $ 70.00. Conclusions While stent cytologic analysis is a common clinical practice, the diagnostic yield and cost effectiveness of the practice must be reevaluated. With the rise of newer diagnostic technologies such as digital cholangioscopy and endoscopic ultrasound-guided fine-needle biopsy, it may be time to “think lean” and acknowledge a sunset for biliary stent cytology.

Non-Metastatic Esophageal Adenocarcinoma: Circulating Tumor Cells in the Course of Multimodal Tumor Treatment

Background: Isolation of circulating tumor cells (CTC) holds the promise to improve response-prediction and personalization of cancer treatment. In this study, we test a filtration device for CTC isolation in patients with non-metastatic esophageal adenocarcinoma (EAC) within recent multimodal treatment protocols. Methods: Peripheral blood specimens were drawn from EAC patients before and after neoadjuvant chemotherapy (FLOT)/chemoradiation (CROSS) as well as after surgery. Filtration using ScreenCell® devices captured CTC for cytologic analysis. Giemsa-stained specimens were evaluated by a cytopathologist; the cut-off was 1 CTC/specimen (6 mL). Immunohistochemistry with epithelial (pan-CK) and mesenchymal markers (vimentin) was performed. Results: Morphologically diverse malignant CTCs were found in 12/20 patients in at least one blood specimen. CTCs were positive for both vimentin and pan-CK. More patients were CTC positive after neoadjuvant therapy (6/20 vs. 9/15) and CTCs per/ml increased in most of the CTC-positive patients. After surgery, 8/13 patients with available blood specimens were still CTC positive. In clinical follow-up, 5/9 patients who died were CTC-positive. Conclusions: Detection of CTC by filtration within multimodal treatment protocols of non-metastatic EAC is feasible. The rate of CTC positive findings and the quantity of CTCs changes in the course of multimodal neoadjuvant chemoradiation/chemotherapy and surgery.