An advanced non-small cell lung cancer patient with EGFR and KRAS mutations, and PD-L1 positive, benefited from immunotherapy: a case report.

Background: Patients with epidermal growth factor receptor (EGFR)-sensitive mutations have great opportunity to benefit from EGFR-tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). Although the presence of Kirsten rat sarcoma virus (KRAS) mutations is predictive of lack of benefit from EGFR-tyrosine kinase inhibitor (TKI) therapy for NSCLC, patients with KRAS mutations could be more sensitive to programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. However, the application of immunotherapy in EGFR mutated NSCLC patients is still controversial. Case Description: In this study, we reported the case of a 56-year-old NSCLC patient who harbored the mutations of EGFR L858R and KRAS G12D, with a high tumor mutational burden value and positive PD-L1 expression. Considering the EGFR sensitive mutation, gefitinib combined pemetrexed was administered; however, the disease progressed soon after. The patient then underwent combined treatment of bevacizumab (400 mg), camrelizumab (200 mg), and pemetrexed (0.8 mg), and partial response was observed after 4 months. When chemotherapy was removed from the combined treatment, liver metastasis was detected. Interestingly, the disease was well controlled when the combined treatment of bevacizumab, camrelizumab, and pemetrexed was resumed. Overall, the patient benefits lasted more than 17 months. Conclusions: Our results indicated that immunotherapy may be a potential choice in NSCLC with EGFR and KRAS mutations, and combined chemotherapy may effectively increase therapeutic efficiency during combined immunotherapy.

Transferrin-Decorated Protein-Lipid Hybrid Nanoparticle Efficiently Delivers Cisplatin and Docetaxel for Targeted Lung Cancer Treatment.

PURPOSE: Non-small cell lung cancer (NSCLC) therapy faces the barriers including drug resistance. A transferrin-functionalized protein-lipid hybrid nanoparticle (PLHN) was designed loading both cisplatin (CIS) and docetaxel (DTX) for the lung cancer treatment. METHODS: CIS and DTX were loaded into the hybrid nanoparticle and then decorated with transferrin (Tf). The Tf-functionalized protein-lipid hybrid nanoparticle (Tf-CIS/DTX-PLHN) was investigated by determining the release behavior, cytotoxicity in vitro, and anticancer efficiency in vivo. RESULTS: Tf-CIS/DTX-PLHN showed a nano-size of 189.5 ± 5.9 nm, and a surface tested to be -16.9 ± 2.1 mV. Tf-CIS/DTX-PLHN exhibited obviously better antitumor ability in vitro and in vivo compared with the non Tf contained CIS and DTX co-loaded lipid nanoparticles (CIS/DTX-LN), single drug loaded nanoparticles, and free drugs. CONCLUSION: Since remarkable enhanced efficiency of Tf and synergistic effect of the drugs, it could inhibit the lung tumor growth and help with the lung cancer treatment.

Clinical study of pulmonary CT lesions and associated bronchiectasis in 115 convalescent patients with novel coronavirus pneumonia (COVID-19) in China.

A total of 115 convalescent inpatients with COVID-19 were enrolled. According to the results of scans of lung lesions via computed tomography (CT), the patients were divided into mild, moderate, and severe groups. The clinical data of the patients were collected, including age, gender, finger pulse oxygen pressure, ventricular rate, body temperature, etc. The correlation between the clinical indicators and the lesions of high-resolution CT (HRCT) and bronchiectasis was analyzed. Among the 115 patients, 82 had no bronchiectasis and 33 had bronchiectasis. The bronchodilation-prone layers mainly included the left and right lower lobe of the lung. The probability of branching in the inflamed area was greater than that in the noninflamed area in patients with COVID-19. There were significant differences in gender, CT lesion range, and number of incidents of bronchiectasis between noninflamed and inflamed areas (P < 0.05). Moreover, there were significant differences in age, total proportion of CT lesions, volume of CT lesions, and total number of patients with bronchiectasis among the three groups (P < 0.05). CT lesion range was positively correlated with the total number of patients with bronchiectasis and patient age (respectively, r = 0.186, P < 0.05; r = 0.029, P < 0.05). The lesion range in HRCT images of lungs in patients with COVID-19 is correlated with bronchodilation. The larger the lesion, the higher the probability of bronchiectasis and the more incidents of bronchiectasis.

miR-942-5p promotes the proliferation and invasion of human melanoma cells by targeting DKK3.

OBJECTIVE: The purpose of this study was to figure out the dysregulation of miR-942-5p in melanoma and its role in melanoma pathogenesis. METHODS: Quantitative real-time PCR (qRT-PCR) assay was used to determine the change of RNA expression. Protein expression was examined by Western blotting. miRNA target was validated through TargetScan and luciferase assay. Cell migration and invasion were detected by wound healing and transwell assay, respectively. RESULTS: Results of qRT-PCR manifested miR-942-5p were upregulated in melanoma cell. High expression of miR-942-5p in melanoma patients presented a poor prognosis. Upregulation of miR-942-5p accelerated cell proliferation, migration, and invasion in melanoma cells. Cell apoptosis was inhibited by miR-942-5p mimics. Suppression of miR-942-5p by its inhibitor showed the opposite effects in melanoma cells. TargetScan and luciferase assay showed that miR-942-5p directly targeted to the 3'-untranslated region (3'-UTR) of DKK3. Overexpression of DKK3 inhibited GSK-3ß phosphorylation and reduced the expression of ß-catenin in both cytoplasm and nucleus, which were induced by miR-942-5p mimics leading to the activation of Wnt/ß-catenin pathway. CONCLUSION: Upregulation of miR-942-5p was observed in melanoma cells and tissues and significantly associated with a poor prognosis. Though targeting 3'-UTR of DKK3, miR-942-5p could activate Wnt/ß-catenin pathway, resulting in melanoma cell proliferation, migration, and invasion, which promoted the development of melanoma. These results showed that miR-942-5p might be a diagnosis and prognosis biomarker in melanoma.

MicroRNA-222 expression and its prognostic potential in non-small cell lung cancer.

Overexpression of miR-222 has been found in several types of cancers; however, the expression of miR-222 in non-small cell lung cancer (NSCLC) and its prognostic values are unclear. This study aimed to investigate whether the miR-222 expression level is related to clinicopathological factors and prognosis of NSCLC. Through a prospective study, 100 pairs of NSCLC tissues and adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between miR-222 expression and clinicopathological features was analyzed, and the significance of miR-222 as a prognostic factor and its relationship with survival were determined. Results showed that the expression levels of miR-222 were significantly elevated in the NSCLC tissue compared with that in adjacent normal tissue. In addition, Cox's proportional hazards model analysis confirmed that miR-222 high expression level was an independent predictor of poor prognosis. In conclusion, miR-222 overexpression is involved in the poor prognosis of NSCLC and can be used as a biomarker for selection of cases requiring especial attention.

Synergistic effect of lidocaine with pingyangmycin for treatment of venous malformation using a mouse spleen model.

AIMS: To explore whether lidocaine has the synergistic effect with pingyangmycin (PYM) in the venous malformations (VMs) treatment. METHODS: The mouse spleen was chosen as a VM model and injected with different concentration of lidocaine or PYM or jointly treated with lidocaine and PYM. After 2, 5, 8 or 14 days, the mouse spleen tissues were acquired for hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM) analysis, TUNEL assay and quantitative RT-PCR analysis to examine the toxicological effects of lidocaine and PYM on splenic vascular endothelial cells. RESULTS: 0.4% of lidocaine mildly promoted the apoptosis of endothelial cells, while 2 mg/ml PYM significantly elevated the apoptotic ratios. However, the combination of 0.2% lidocaine and 0.5 mg/ml PYM notably elevated the apoptotic ratios of splenic cells and severely destroyed the configuration of spleen, compared to those of treatment with 0.5 mg/ml PYM alone. CONCLUSION: Lidocaine exerts synergistic effects with PYM in promoting the apoptosis of mouse splenic endothelial cells, indicating that lidocaine possibly promotes the therapeutic effects of PYM in VMs treatment via synergistically enhancing the apoptosis of endothelial cells of malformed venous lesions.