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BACKGROUND@#Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.@*METHODS@#Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups.@*RESULTS@#Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed.@*CONCLUSION@#Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.@*CLINICAL TRIAL REGISTRATION@#https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Immune Checkpoint Inhibitors/therapeutic use , Retrospective Studies , Brain Neoplasms/geneticsABSTRACT
Non-small cell lung cancer (NSCLC) accounts for 85% of total cases of lung cancer, which has the highest incidence and mor-tality in China. Most patients with lung cancer present with advanced stage disease at the time of diagnosis. With the limited develop-ment of cytotoxic chemotherapy for NSCLC therapy, median overall survival in patients receiving platinum-based doublet chemothera-py has been less than one year in several trials. To date, anti-angiogenesis agents combined with chemotherapy, small molecule tyro-sine kinase inhibitors (TKI) and immune checkpoint inhibitors were commonly applied in NSCLC instead of purely chemotherapy, which makes a great breakthrough in NSCLC therapy. This review summarizes and discusses the application of anti-angiogenic therapy in ad-vanced NSCLC.
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Escherichia coli (E. coli) FadR regulator plays dual roles in fatty acid metabolism, which not only represses the fatty acid degradation (fad) system, but also activates the unsaturated fatty acid synthesis pathway. Earlier structural and biochemical studies of FadR protein have provided insights into interplay between FadR protein with its DNA target and/or ligand, while the missing knowledge gap (esp. residues with indirect roles in DNA binding) remains unclear. Here we report this case through deep mapping of old E. coli fadR mutants accumulated. Molecular dissection of E. coli K113 strain, a fadR mutant that can grow on decanoic acid (C10) as sole carbon sources unexpectedly revealed a single point mutation of T178G in fadR locus (W60G in FadRk113). We also observed that a single genetically-recessive mutation of W60G in FadR regulatory protein can lead to loss of its DNA-binding activity, and thereby impair all the regulatory roles in fatty acid metabolisms. Structural analyses of FadR protein indicated that the hydrophobic interaction amongst the three amino acids (W60, F74 and W75) is critical for its DNA-binding ability by maintaining the configuration of its neighboring two β-sheets. Further site-directed mutagenesis analyses demonstrated that the FadR mutants (F74G and/or W75G) do not exhibit the detected DNA-binding activity, validating above structural reasoning.
Subject(s)
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase , Genetics , Metabolism , Amino Acid Sequence , Bacterial Proteins , Chemistry , Genetics , Metabolism , DNA, Bacterial , Chemistry , Metabolism , Escherichia coli , Genetics , Metabolism , Escherichia coli Proteins , Genetics , Metabolism , Fatty Acid Synthase, Type II , Genetics , Metabolism , Fatty Acids , Metabolism , Gene Expression Regulation, Bacterial , Hydro-Lyases , Genetics , Metabolism , Hydrophobic and Hydrophilic Interactions , Lipid Metabolism , Models, Molecular , Molecular Sequence Data , Mutation , Protein Binding , Protein Structure, Secondary , Repressor Proteins , Chemistry , Genetics , Metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Signal TransductionABSTRACT
Objective To investigate the influence of application of local anesthesia with lidocaine on bronchial lavage fluid (BLF) pseudomonas aeruginosa culture and drug sensitivity in cases with lung infection .Methods Two hundred and seventy speci-men of BLF were collected from 135 patients with infection of lung .And BLF were collected directly from right-broncho in control group ,and from left-broncho in lidocaine group .The outcome of pseudomonas aeruginosa culture and drug sensitivity were com-pared in the two groups .Results Fourty-two cases were postitive in BLF pseudomonas aeruginosa culture in the control group ,and 40 cases were postitive in lidocaine group .The positive rates were 31 .11% and 29 .63% ,respectively .There were no significance between the two groups (P<0 .001) .Compared with the control group ,the sensitive strains of pseudomonas aeruginosa were obvi-ously less and the drug tolerance strains were much more in lidocaine group for Ciprofloxacin and Levofloxacin (P<0 .05) .Howev-er ,there were no influence for drugs such as Piperacillin/Tazobactam and Ceftazidime ,etc .Conclusion 2% lidocaine has no influ-ence on the outcome of BLF pseudomonas aeruginosa culture .But it may reduce the drug sensitivity of Ciprofloxacin and Levofloxa-cin in cases with infection of lung .
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To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin-adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU-87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer.
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To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin-adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU-87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer.
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AIM: To investigate the relationship among MCP-1 and monocyte chemoattract protein activity (MCA) and pathogenesis of lung cancer. METHODS: 173 patients were involved in the study and divided into three groups: group A: lung cancer group (60 patients); group B: benign lung disease group (55 patients) and group C: healthy control group (58 patients). MCP-1 level and MCA in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: The concentration of MCP-1 and MCA in BALF in group A were much higher than those in group B and group C (P
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0.05]. CONCLUSIONS: The currents of voltage-gated potassium channel was inhibited by chronic hypoxic. The inhibitory effect of cGMP on currents of voltage-gated potassium channel in PASMCs from both normal and chronic hypoxic rats may be probably through the phosphorylation of voltage-gated potassium channel.
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OBJECTIVE To explore the isolation,distributive characteristics and drug resistance of Acinetobacter baumannii producing AmpC enzyme in nosocomial infection.METHODS The distributive sections and infected parts of 42 A.baumannii strains in nosocomial infection were analyzed,and three dimensional test was used to(detect) AmpC enzyme.RESULTS Among them 18(42.86%) strains were AmpC positive.Among 40 strains of A.baumannii in non-nosocomial infection,6(15.00%) strains were AmpC positive.A.baumannii in nosocomial(infection) in clinical sections was mainly discovered in burn department,and the respiratory tract and skin soft tissue were the main infected sites(90%).The drug resistance in nosocomial infection was obviously higher than that of A.baumannii in non-nosocomial one.CONCLUSIONS The isolated rate and drug resistance rate of A.baumannii producing AmpC enzyme are rather high in nosocomial infection.It′s(neccessary) to take measures to prevent the nosocomial infection caused by A.baumannii.
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OBJECTIVE To investigate multidrug-resistant bacteria infection in newborn department,for rationally use of antibiotic. METHODS A total of 1927 patients in newborn department scientific were investigated for their multidrug-resistant bacteria infection. RESULTS There were no statistical differences of multidrug resistance bacteria infection in the four seasons. From 1927 newborn patients,128 patients were with multidrug-resistant bacteria infection,the positive rate was 6.64%,83.59% origin of Society area,in 128 patients children of multidrug resistance bacteria infection,happen infection were 134 example 86.57% were respiratory tract infection,70.83% resistance bacteria including Klebsiella pulmonary,appear multidrug resistance bacteria infection previous 62.28% were use antibiotic. CONCLUSIONS Newborn deartment The multidrug resistance bacteria infection is related to occurved in newborn department abuse and unrationaly use of antibiotics. Its should be strengthened to supervise and manage.