Successful response to the combination of immunotherapy and chemotherapy in cholangiocarcinoma with high tumour mutational burden and PD-L1 expression: a case report.

BACKGROUND: Cholangiocarcinoma, or bile duct cancer, is a gastrointestinal cancer with limited therapeutic options and a poor outcome. Studies have revealed that some major driver genes are associated with cholangiocarcinoma, but no targeted therapies have been approved. Immune checkpoint inhibitors, which are represented by inhibitors of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), have emerged as a potential therapy for multiple types of solid cancers. CASE PRESENTATION: A 53-year-old female presented with postoperative recurrence of PD-L1-positive intrahepatic cholangiocarcinoma with a high tumour mutational burden. This patient exhibited a marked response to the combination of anti-PD-1 immunotherapy and chemotherapy. CONCLUSIONS: As far as we know, this is the first case report on the success of the combination of immunotherapy and chemotherapy for advanced cholangiocarcinoma with PD-L1 positivity and a high tumour mutational burden.

Hypomethylation-Mediated Upregulation of NFE2L3 Promotes Malignant Phenotypes of Clear Cell Renal Cell Carcinoma Cells.

This work aimed to study the effect of NFE2 like bZIP transcription factor 3 (NFE2L3) on clear cell renal cell carcinoma (ccRCC) cells and whether NFE2L3 expression was mediated by DNA methylation. Twenty-one ccRCC patients were collected. The gene methylation and expression data of TCGA-KIRC were accessed from TCGA. Candidate methylation driver genes were identified by "MethylMix" package, and finally, NFE2L3 was selected as the target gene. The methylation of NFE2L3 was assayed by Ms PCR and QMSP. mRNA level of NFE2L3 was analyzed by qRT-PCR. Protein level of NFE2L3 was measured by Western blot. Demethylation was performed with methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR). Proliferative, migratory, and invasive abilities of ccRCC cells were assayed via cell colony formation assay, scratch healing assay, and transwell assay, respectively. Analysis of TCGA database presented that DNA hypomethylation occurred in the NFE2L3 promoter region in ccRCC tissues. NFE2L3 was significantly upregulated in ccRCC tissues and cells. Its expression in cells treated with 5-Aza-CdR was proportional to the concentration of methylation inhibitor. In cell function experiments, overexpressing NFE2L3 or demethylation could stimulate proliferation, migration, and invasion abilities of ccRCC and normal cells. 5-Aza-CdR treatment rescued repressive impact of knockdown NFE2L3 on malignant phenotypes of ccRCC and normal cells. DNA hypomethylation could induce high expression of NFE2L3 and facilitate malignant phenotypes of ccRCC cells. These results may generate insights into ccRCC therapy.

Case report: A case of complete clinical response in a patient experiencing high microsatellite instability unresectable colon cancer being treated with a PD-L1 inhibitor after interstitial pneumonia.

Immune checkpoint inhibitors (ICI) have dramatically transformed the treatment landscape for metastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) or high microsatellite instability (MSI-H). Envafolimab, a novel programmed death-1 ligand 1 (PD-L1) inhibitor, has been reported to be efficient and safe for the management of advanced MSI-H/dMMR solid tumors. Here, we report the case of a 35-year-old female patient with MSI-H/dMMR mCRC who was treated with envafolimab following mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) plus bevacizumab. While suffering from interstitial pneumonia after chemotherapy, the patient achieved a complete clinical response with the use of envafolimab without additional adverse events. Thus, PD-L1 inhibitors may be potential candidates for treating patients with MSI-H/dMMR mCRC.

3D-Heterojunction Based on Embedded Perovskite Micro-Sized Single Crystals for Fast Photomultiplier Photodetectors with Broad/Narrowband Dual-Mode.

A fast photomultiplier photodetector with a broad/narrowband dual mode is implemented using a new 3D heterostructure based on embedded perovskite micro-sized single crystals. Because the single-crystal size is smaller than the electrode size, the active layer can be divided into a perovskite microcrystalline part for charge transport and a polymer-embedded part for charge storage. This induces an additional radial interface in the 3D heterojunction structure, and allows a photogenerated built-in electric field in the radial direction, especially when the energy levels between the perovskite and embedding polymer are similar. This type of heterojunction has a small radial capacitance that can effectively reduce carrier quenching and accelerate the carrier response. By controlling the applied bias direction, up to 300-1000% external quantum efficiency (EQE) and microsecond response can be achieved not only in the wide range of ultraviolet to visible light from 320 to 550 nm, but also in the narrow-band response with a full width at half minimum (FWHM) of 20 nm. This shows great potential for applications in integrated multifunctional photodetectors.

Spatial Identification of "Zeroth Defect" Formation in Organic Light-Emitting Diodes by Multispectral Mappings.

In recently developed organic semiconductors, the continuously improving sample purity makes the stability of the chemical bonds of organic materials themselves become a key factor in device stability, which provides greater uncertainty for the generation of "zeroth defect", and the spatial resolution of performance at different positions becomes particularly important. In this work, complete maps of electroluminescent, photoluminescent, and Raman scattering in the same area on an organic light-emitting diode during its operation have been achieved with a confocal spectrometer with multiple laser sources. The different spectral characters help to establish different regions and suggest the mechanism of degradation. In particular, Raman scattering has been shown to be very sensitive in a multilayer device to a change in thickness of several nanometers. In amorphous films with few defects, the very weak film uniformity, including the thickness and degree of aggregation, would induce dramatic degradation. The relatively thin and/or loosely textured region easily locally overheats and has the highest probability of "zeroth defect" generation. This method has high spatial resolution, a low level of damage to samples, good reproducibility, and multiple interconnected pieces of information, which is significant for online quality prediction and mechanistic analysis.

Diffusion interface layer controlling the acceptor phase of bilayer near-infrared polymer phototransistors with ultrahigh photosensitivity.

The narrow bandgap of near-infrared (NIR) polymers is a major barrier to improving the performance of NIR phototransistors. The existing technique for overcoming this barrier is to construct a bilayer device (channel layer/bulk heterojunction (BHJ) layer). However, acceptor phases of the BHJ dissolve into the channel layer and are randomly distributed by the spin-coating method, resulting in turn-on voltages (Vo) and off-state dark currents remaining at a high level. In this work, a diffusion interface layer is formed between the channel layer and BHJ layer after treating the film transfer method (FTM)-based NIR phototransistors with solvent vapor annealing (SVA). The newly formed diffusion interface layer makes it possible to control the acceptor phase distribution. The performance of the FTM-based device improves after SVA. Vo decreases from 26 V to zero, and the dark currents decrease by one order of magnitude. The photosensitivity (Iph/Idark) increases from 22 to 1.7 × 107.

Case report: Long-term clinical benefit of pyrotinib therapy following trastuzumab resistance in HER2-amplification recurrent mucinous ovarian carcinoma.

Advanced or recurrent mucinous carcinoma of the ovary minimally responds to current cytotoxic treatments and has a poor prognosis. Despite multimodal treatment with chemotherapy and surgery, most patients ultimately progress and require palliative systemic therapy. Anti-HER2 therapy has been demonstrated to be an effective strategy for the treatment of HER2-positive breast cancer. However, the role of anti-HER2 therapy in ovarian cancer remains largely unknown. Here, we report the case of a young woman with FIGO Stage IIIc recurrent mucinous ovarian carcinoma (MOC) who developed trastuzumab resistance and disease progression following cross-treatment with trastuzumab combined with pertuzumab. HER2 amplification was discovered using next-generation sequencing (NGS). The patient then received bevacizumab, and pyrotinib (an irreversible HER2 antagonist) plus capecitabine treatment, and achieved a long-term clinical benefit for 22 months. Pyrotinib combined with bevacizumab is a potential treatment for MOC patients who are heavily pretreated and harbor a HER2 amplification. Our case may provide valuable treatment information for patients with advanced or recurrent MOC.

Clinical characteristics, risk factors, and outcomes after adjuvant radiotherapy for patients with thymoma in the United States: analysis of the Surveillance, Epidemiology, and End Results (SEER) Registry (1988-2013).

PURPOSE: The surgery with adjuvant radiation for the treatment of thymoma is still debated. The aim of this study was to examine the efficacy of postoperative radiotherapy (PORT) in a population-based registry of patients with thymoma. MATERIALS AND METHODS: We conducted a retrospective analysis of the Surveillance, Epidemiology, and End Results database to compare the outcomes of patients with thymoma who received surgery with or without PORT. RESULTS: Among the 2234 patients of this study, the surgery with PORT group had a longer mean overall survival (OS) and cancer-specific survival (CSS) than did the surgery without PORT group (OS: 172.3 vs. 155.3 months, p = .005; CSS: 247.3 vs. 241.8 months, p = .04). PORT significantly improved OS and CSS of patients with stage III/IV disease, but decreased CSS for those with stage I/IIA disease. Although the surgery with PORT group had a higher rate of secondary cancers, the between-group difference in the disease-free interval was not significant. CONCLUSIONS: PORT provides a significant benefit for patients with thymoma, particularly those with advanced disease. However, it also increases the risk of a second malignancy. We suggest that treatment guidelines should adopt a more positive stance on the use of PORT.