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4 recordsLinked to original sources
PubMed2026

Targeting super-enhancer-driven SKIL transcription by CDK7 inhibitor THZ1 to suppress gastric cancer progression.

BACKGROUND: Gastric cancer (GC) is a lethal malignancy characterized by high incidence, mortality, and limited treatment options. Transcriptional addiction is a key cancer hallmark that drives tumor pathogenesis, making its inhibition a promising therapeutic strategy for GC. The study aims to investigate the roles and mechanisms of super-enhancer (SE)-driven oncogenic transcriptional addiction in GC progression and to identify novel targetable vulnerabilities. METHODS: We utilized cellular and animal models to assess the effects of THZ1 treatment and CDK7 knockdown on GC progression. RNA sequencing was employed to elucidate the potential molecular mechanism of THZ1 treatment. ChIP-seq was performed to establish SE landscape in GC. Integrative analysis of transcriptomic and SE profiling was used to identify THZ1-targeted oncogenic genes. Rescue experiments were conducted to confirm that THZ1 treatment suppresses GC malignant progression by targeting SE-driven SKIL transcription. RESULTS: GC cells exhibited pronounced sensitivity to THZ1 compared to normal gastric mucosa cells, and the treatment potently suppressed tumor growth and migration in both cellular and animal models. CDK7 was significantly upregulated in GC tissues, and its knockdown inhibited malignant progression in vitro and in vivo, whereas its overexpression accelerated tumor progression. Mechanistically, SE-driven oncogenic transcriptional amplification underlies GC cell susceptibility to THZ1, supported by the identification of novel oncogenic genes such as SKIL. SKIL, a key Hippo pathway regulator, was highly expressed in GC cells, and its elevated expression predicted poor patient prognosis. SKIL silencing attenuated malignant phenotypes, while its overexpression diminished THZ1’s suppression of GC cell proliferation and migration. CONCLUSION: Our findings demonstrate that THZ1 inhibits GC progression by disrupting SE-driven oncogenic transcription, thereby offering CDK7 inhibition as a promising therapeutic intervention for GC.

Stomach Neoplasms↗
PubMed1975

[Radiological aspects of esophageal intramural diverticulosis].

The 9th observation of esophageal intramural diverticulosis is reported. The findings are compared with those of former publications. Clinically dysphagia is a leading symptom. Suction biopsy proved diverticulosis being the correct interpretation for radiological findings. The etiology is discussed. The change between symptom-free intervals with diverticulosis only and episods of dysphagia by secondary inflammation (reflux esophagitis, moniliasis, stenosis) stresses the importance of such secondary complications. These inflammations can hide the real diagnosis for a long time. The radiological findings are the key for diagnosis, however, they can be very small for years. During this period a diagnosis can only be achieved by knowledge of the disease and the skilful search for early symptoms.

Adult↗
PubMed1975

The history of controlled hypotension.

As the physiology of deliberate hypotension has been unravelled, and as each new pharmacological agent has become available which either depresses or blocks peripheral vascular tone, depresses myocardial performance, or interferes with the conducting tissues within the myocardium, its possible incorporation into the armamentarium of the anaesthetist who offers induced hypotension has been considered. The result has been a sequence of variations in technique of characteristically recognizable vintage. No matter how the condition of induced hypotension is produced, there is usually vasodilatation, and the characteristic disturbance in physiology is of a loss of postural reactivity in the cardiovascular system. Important lessons have been learned concerning the management of shock states. Though it is difficult to evaluate the morbidity of deliberate induced hypotension, and terms such as "physiological trespass" have been used by its antagonists, it would appear that a well-considered and skilfully managed controlled hypotension is no more of a physiological trespass than anaesthesia, nor indeed than the trespass of the surgeon's knife itself.

Anesthesia↗
PubMed1979

[New materials on the history of veterinary medicine in Bulgaria].

Several tens of ritual plates are preserved in Bulgaria on which elements of glorification are found of god Mithras who gained popularity particularly in the 1st-IIIrd century in the regions of Thrace and today's North Bulgaria, then provinces of the Eastern Roman Empire. Mithras seemed to be respected by slaves, soldiers, and merchants alike, but was also an exemplar to the Roman emperors, being considered by them as Sol invictus or Deo invicto. The central scene in all plates is that of Mithras tauroctonus (Mithras, the killer of bulls). This scene is likewise of interest to veterinarians as it shows that in such early epoch the people that lived within the territory of Bulgaria of today used a method for the felling of large animals, the elements of which--fixing the head and bending it backwards, fastening the thorax with a belt or another loop, loading the animal's back--are still existing and are used in a number of modern methods of felling (that of Hess, the Caucasian way of felling, the Chinese one of Dou-Chan-Than, etc.) Besides, the people of ancient time knew that ruminants have an incomplete upper dentition. They skilfully employed this to bring animals that had to be felled into an unusual nonphysiologic posture. Not sooner than 16 centuries prior to the preformists (the spermists) they supported the concept that the testes were the source of life.

Bulgaria↗