ABSTRACT
Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01-TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 µM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Design , Enzyme Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Thiourea/pharmacology , A549 Cells , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Molecular Structure , Proto-Oncogene Mas , Proto-Oncogene Proteins p21(ras)/metabolism , Structure-Activity Relationship , Thiourea/chemical synthesis , Thiourea/chemistryABSTRACT
@#Surgery is an essential method of comprehensive treatment for lung cancer, but it also impairs patients’ cardiopulmonary function. A subset of patients who undergo surgery may suffer from postoperative complications, and even death. Preoperative pulmonary rehabilitation is a part of enhanced recovery after surgery, and can improve patients' cardiopulmonary function, reduce postoperative complication rate and shorten hospital stay. It has been already demonstrated a great value in lung cancer surgery. In this review, we summarized the three important components of preoperative pulmonary rehabilitation, including smoking cessation, chest physical therapy, and preoperative exercise training. Moreover, this review outlined the development of pulmonary rehabilitation for lung malignancies, aiming to promote its application and standardization.
ABSTRACT
A 26-year-old man was admitted to Beijing Friendship Hospital, Capital Medical University (Beijing, China) with a 4-day history of headache, moderate fever and numbness in the right upper limb. Prior to this, the patient had been diagnosed with cerebral hemorrhage by computed tomography (CT) scan upon visiting a local hospital. Chest X-ray revealed multiple lesions in the lungs. Following referral, no abnormalities were found elsewhere, including in the testes, during a physical examination. Additional examination of other tumor biomarkers was unremarkable, and the initial suspicion of parasitic infection was ruled out. Tests revealed extremely high levels of ß-human chorionic gonadotropin (>200,000 mIU/ml). In addition, CT scans showed multiple metastases in the head, lungs, liver and kidneys. An ultrasound-guided Tru-Cut biopsy of the liver was performed in order to form a definitive diagnosis. Although the patient was treated with mannitol to reduce intracranial pressure, and with cefoperazone sodium and sulbactam sodium to fight infection, the patient succumbed to a cerebral hernia on the fourth day of hospitalization. Following this, the ultrasound-guided Tru-Cut liver biopsy result was received, which suggested a diagnosis of choriocarcinoma.
ABSTRACT
Objective To study the effect of nursing intervention on preoperative anxiety of patients with gynecological carcinoma.Methods 60 patients with gynecological carcinoma in our hospital who were to receive operations were randomly distributed into the control group and the intervention group with 30 in each group.The control group was given routine nursing,while the intervention group received nursing intervention based upon routine nursing.Indexes such as preoperative anxiety,sleeping quality and satisfaction degree to nursing care were evaluated within them.Results Through targeted nursing intervention preoperative anxiety of patients in the intervention group alleviated,their confidence enhanced and satisfaction degree to nursing care improved compared to those of the control group.Conclusions Targeted nursing intervention can reduce preoperative anxiety of patients with gynecological carcinoma and increase satisfaction degree to nursing care.
ABSTRACT
The serum soluble interleukin-2 receptor (sIL-2R) in 66 patients with malignant tumorwas measured by sandwith ELISA technique in this paper,39 health students are as control.Theresults show the level of sIL-2R was obvious higher than the controls (P
