Disitamab Vedotin plus anti-PD-1 antibody show good efficacy in refractory primary urethral cancer with low HER2 expression: a case report.

Primary urethral carcinoma (PUC) has a low incidence, but with high aggressiveness. Most of the patients are found in late stage, with poor prognosis. At present, chemotherapy is still the main treatment for metastatic PUC, but it has limited effect. Here, we report a case of metastatic PUC with low HER2 expression that developed disease progression after multiline therapy including chemotherapy, programmed death-1 (PD-1) inhibitors and multi-targeted receptor tyrosine kinase (RTK) inhibitor. After receiving Disitamab Vedotin(a novel antibody drug conjugate, ADC) and toripalimab (a PD-1 inhibitor), the patient achieved persistent PR, and the PFS exceeded 12 months up to now. Our report indicates that, despite the patient of metastatic PUC has low expression of HER2, it is still possible to benefit from Disitamab Vedotin combined with PD-1 inhibitor, which may reverse the drug resistance of PD-1 inhibitor and chemotherapy to a certain extent. But larger sample studies are needed to determine the efficacy of this treatment strategy and its impact on survival.

A novel SETD3-ALK fusion in lung adenocarcinoma and sustained clinical response to crizotinib.

OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a vital driving mutation in non-small cell lung cancer (NSCLC). ALK rearrangements may involve different breakpoints and multiple fusion partners, presenting different therapeutic responses. There are no standard treatment options for rare ALK rearrangements. Here, we report a case of advanced lung adenocarcinoma (LUAD) harboring a novel SET domain containing 3 (SETD3)-ALK fusion and sensitive to crizotinib, which has not been previously reported. MATERIALS AND METHODS: Molecular and pathological features were confirmed using percutaneous lung biopsy guided by computed tomography (CT), immunohistochemical (IHC) staining and next-generation sequencing (NGS). RESULTS: NGS revealed that a novel SETD3-ALK fusion was detected in the patient with LUAD, and IHC analysis confirmed that this fusion had functional expression. The patient had a progression-free survival (PFS) over 16 months after crizotinib treatment (250 mg b.i.d.), with ongoing clinical response. CONCLUSION: This case introduces a novel and meaningful ALK fusion type in LUAD with sustained sensitivity to crizotinib, providing a reference to the treatment of similar cases with SETD3-ALK fusion in the future.

[Degradation of lignocellulose in the corn straw by Bacillus amyloliquefaciens MN-8].

Microbial degradation of lignocellulose is one of the key problems that need to be solved urgently in the process of utilizing biomass resource. Bacillus amyloliquefaciens MN-8 is our previously isolated bacterium capable of degrading lignin. To determine the capability of strain MN-8 to degrade lignocellulose of corn straw, B. amyloliquefaciens MN-8 was inoculated and fermented with solid-state corn straw powder-MSM culture medium. The changes in the enzyme activity and degradation products of lignocellulose were monitored in the process of fermentation using the FTIR and GC/MS. The results showed that B. amyloliquefaciens MN-8 could produce lignin peroxidase, manganese peroxidase, cellulase and hemicellulase enzymes. The activities of all these enzymes reached the peak after being incubated for 10-16 days, and the highest enzyme activities were 55.0, 16.7, 45.4 and 60.5 U · g(-1), respectively. After 24 d of incubation, the degradation percentages of lignin, cellulose and hemicellulose were up to 42.9%, 40.6% and 27.1%, respectively. The spectroscopic data by FTIR indicated that the intensities of characteristic absorption peaks of lignin, cellulose and hemicellulose of the corn straw were decreased, indicating that the lignocellulose was degraded partly after being fermented by B. amyloliquefaciens MN-8. GC/MS analysis also demonstrated that strain MN-8 could degrade lignocellulose efficiently. It could depolymerize lignin into some monomeric compounds with retention of phenylpropane structure unit, such as amphetamine, benzene acetone and benzene propanoic acids, by the rupture of ß-O-4 bond connected between lignin monomer, and it further oxidized some monomer compounds into Cα carbonyl compounds, such as 2-amino-1-benzeneacetone and 4-hydroxy-3,5-dimethoxy-acetophenone. The GC/MS analysis of the degradation products of cellulose and hemicellulose showed that there were not only monosaccharide compounds, such as glucose, mannose and galactose, but also some glycolysis products including formic acid, acetic acid, propionic acid, 1,1-ethanediol and 3-hydroxy butyric acid. Our results demonstrated that B. amyloliquefaciens MN-8 is capable of degrading lignocelluse of the corn straw effectively and the degradation capacity depends on the lignocellulase activity.