SEARCH · PubMed Health

Results for “SKIL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

7 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

Skin collagen biosynthesis in patients with rheumatoid arthritis treated with D-penicillamine.

Collagen biosynthesis was measured in skin biopsies taken from 13 patients with rheumatoid arthritis before and after at least 6 months' continuous treatment with D-penicillamine, 1.0 g/day. There was a significant 36% reduction in mean collagen biosynthesis (p less than 0.0125) as assayed by 14C-hydroxyproline formation from 14C-proline during 24 h of tissue culture. The changes in 14C-hydroxyproline formation were correlated with the total doses of D-penicillamine taken (r = 0.71, p less than 0.01) and the falls in ESR (r = 0.72, p less than 0.01). No significant change in general protein syntehsis was observed. 500 microgram/mlD-penicillamine added to skil cultures in vitro inhibited both collagen and general protein synthesis (p less than 0.01). It is suggested that the clinical improvement induced by D-penicillamine could reflect an inhibition of collagen proliferation in the synovium.

Adult↗

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↗

PubMed1979

[Five-year-cure rate of laryngeal cancer in the Kiel clinic. Report of 216 cases from 1960 to 1967 (then director: Prof. Dr. E. Müller) with special reference to indications for surgical or orthovolt x-ray therapy].

Report about the five-years-cure of all cases of carcinoma of the larynx, the Kiel-University-ORL-Department had to engage in with diagnostical and therapeutical treatment within a period of 7 years. Out of the total of 216 patients the absolute survival rate was 144 (= 66,7%) after five years. Cure rate was the best with carcinoma of the true vocal cord (72,8%), less satisfactory with carcinoma of the supraglottic region (61,1%), only 5/14 with carcinoma of the marginal region, and only 2/8 with advanced and widespread tumours of undefinable origin. After comparing the distribution of the total of our patients with those of other authors, our system of diagnosis, staging, and classification is described in detail being the basis for a skilful choice of primary surgical therapy on the one hand or primary irradiation on the other hand (in our cases orthovolt-X-ray). Both the primary treatment and treatment of recurrence-cases are described in detail, differing from descriptions and claims of other authors for "modern" therapy in many items. Nevertheless we have comparatively very good results, they demand a critical standpoint towards new therapeutical methods. In our opinion close collaboration between laryngologists and radiotherapists concerning classification of tumours, staging and choice of therapy, treatment and post-clinical observation is the fundamental condition for obtaining good and better results in treatment of laryngeal carcinoma.

Female↗

PubMed1976

[Radiotherapy of inflammatory diseases -- indicated still today? (author's transl)].

The good response of inflammatory diseases to a low dose radiotherapy is well known. Mainly, this fact is based on experiences made in the time before antibacterial chemotherapy area. In this study our results are presented which were obtained by treating 90 patients with radiotherapy in the last years, exlusively. With respect to the end of the treatment a success rate of more than 90% was achieved. This result was compared with literature and with own findings from radiotherapy of patients with degenerative joint diseases. From the viewpoint of radio-protection the radiotherapy should be initiated as early as possible because in these cases better results could be attained at low doses. Especially, the radiotherapy of the following diseases seems to be favourable: parotitis, mastitis, abscess, furuncle, paronychia and panaritium. Besides the complications and risks of the chemotherapy the somatic and genetic radiation injuries are discussed. When radiation therapy is applied skilfully the side effects of a locally and regionally limited therapy may be neglected. It is recommended to extend the indication for radiotherapy of inflammatory diseases.

Abscess↗