Remdesivir use in the coronavirus disease 2019 pandemic: A mini-review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

Pin1 coordinates HDAC6 upregulation with cell migration in lung cancer cells.

Histone deacetylase 6 (HDAC6) controls many cellular processes via its catalyzing deacetylation of downstream substrates or interacting with its partner proteins. Dysregulation of HDAC6 signaling links to many diseases. Our previous study has been reported peptidyl-prolyl cis/trans isomerase, and NIMA-interacting 1 (Pin1) involving in HDAC6-mediated cell motility. To gain insight into precisely coordination of HDAC6 and Pin1 in cell migration, shRNA-mediated gene silencing and ectopic expression were applied to manipulate protein expression level to evaluate relationship between HDAC6 and Pin1 expression. Quantitative RT-PCR and the cycloheximide (CHX) chase assay resulted in HDAC6 expression is correlated with Pin1 level in H1299 cells. It hints that the Pin1 increases HDAC6 expression through increased transcripts and posttranslational stabilization. Furthermore, wound healing assay and transwell invasion assay evidenced the contribution of Pin1 on cell motility in H1299 cells. Our data suggest that Pin1 acts as an important regulator to manage HDAC6 expression for cell motility in lung cancer cells.

The extracts of Astragalus membranaceus overcome tumor immune tolerance by inhibition of tumor programmed cell death protein ligand-1 expression.

A polysaccharide isolated from the radix of Astragalus membranaceus, called PG2, used in traditional Chinese medicine, with potential hematopoiesis inducing and immunomodulation activities. PG2 extracted from A. membranaceus has been demonstrated as a novel alternative medicine for cancer patients. Recently, we demonstrated that PG2 enhanced chemotherapy through bystander effect and reduced the expression of indoleamine 2, 3-dioxygenase 1 in tumor cells. Many tumors have been proven to have a high expression of programmed cell death protein ligand-1 (PD-L1), which binds with programmed cell death protein-1(PD-1) in immune cells, thus causing immune tolerance within the tumor microenvironment. With decreased expression of PD-L1, increased immune response can be observed, which might be helpful when developing tumor immunotherapy. The antitumor therapeutic effect mediated by PG2 may associate with an inflammatory immune response at the tumor site. However, the molecular mechanism that by which PG2 inhibits PD-L1 is still incompletely known. The expression of PD-L1 was decreased after tumor cells were treated with PG2. In addition, the cell signaling pathway in tumor cells was evaluated by Western blotting analysis after PG2 treatment. PG2 can downregulate the expression of PD-L1 on the cell surface via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase beta-1 (p70S6K) pathway. In conclusion, our results indicate that PG2 inhibits PD-L1 expression and plays a crucial role in immunotherapy, which might be a promising strategy combined with other treatments.

Clinical efficacy of concurrent bevacizumab for malignant ascites in nonsquamous cell carcinoma of the lung.

PURPOSE: Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. METHODS: We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms "lung cancer," "peritoneal carcinomatosis" and "malignant ascites" to find other studies reporting experience of such treatment. RESULTS: Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression-free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies. CONCLUSIONS: Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab-based treatment may serve as one effective treatment strategy for non-squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.

Port type is a possible risk factor for implantable venous access port-related bloodstream infections and no sign of local infection predicts the growth of gram-negative bacilli.

BACKGROUND: Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial. METHODS: We retrospectively reviewed all patients who received IVAPs at a Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous port, BardPort® 6.6 fr (Bard port) and Autosuture Chemosite® 7.5 fr (TYCO port) were used. All patients with clinically proven venous port-related BSIs were enrolled. RESULTS: A total of 552 patients were enrolled. There were 34 episodes of IVAP-related BSIs during the study period for a total incidence of 0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95% confidence interval (CI), 1.688-29.904), p = 0.0075), age > 65 years (HR = 2.320 (95 % CI, 1.179-4.564), p = 0.0148), and lung cancer (HR = 5.807 (95% CI, 2.946-11.447), p < 0.001) were risk factors for port infections. We also found that no local sign of infection was significantly associated with the growth of gram-negative bacilli (p = 0.031). CONCLUSIONS: TYCO venous ports, age > 65 years, and lung cancer were all significant risk factors for IVAP-related BSIs, and no sign of infection was significantly associated with the growth of gram-negative bacilli.

Risk factors for venous port migration in a single institute in Taiwan.

BACKGROUND: An implantable port device provides an easily accessible central route for long-term chemotherapy. Venous catheter migration is one of the rare complications of venous port implantation. It can lead to side effects such as pain in the neck, shoulder, or ear, venous thrombosis, and even life-threatening neurologic problems. To date, there are few published studies that discuss such complications. METHODS: This retrospective study of venous port implantation in a single center, a Taiwan hospital, was conducted from January 2011 to March 2013. Venous port migration was recorded along with demographic and characteristics of the patients. RESULTS: Of 298 patients with an implantable import device, venous port migration had occurred in seven, an incidence rate of 2.3%. All seven were male and had received the Bard port Fr 6.6 which had smaller size than TYCO port Fr 7.5 and is made of silicon. Significantly, migration occurred in male patients (P = 0.0006) and in those with lung cancer (P = 0.004). Multivariable logistic regression analysis revealed that lung cancer was a significant risk factor for port migration (odds ratio: 11.59; P = 0.0059). The migration rate of the Bard port Fr 6.6 was 6.7%. The median time between initial venous port implantation and port migration was 35.4 days (range, 7 to 135 days) and 71.4% (5/7) of patients had port migration within 30 days after initial port implantation. CONCLUSIONS: Male sex and lung cancer are risk factors for venous port migration. The type of venous port is also an important risk factor.

The effect of chemotherapy with cisplatin and pemetrexed for choroidal metastasis of non-squamous cell carcinoma.

PURPOSE: Choroidal metastasis from lung cancer is very rare in the clinical setting. Treatment for lung cancer with symptomatic choroidal metastasis remains uncertain because of the rarity of such cases. METHODS: We performed a retrospective study on symptomatic choroidal metastasis from lung cancer at the Kaohsiung Medical University Hospital from January 2010 to August 2011. In addition, we also performed literature review of all such patients (or of cancers with choroidal metastasis) treated with systemic chemotherapy. RESULTS: In our study, a total of 226 lung cancer patients were registered during the study period, and only four had choroidal metastasis (4/226, 1.77 %). Three were female (75 %) and one was male, with a mean age of 40.74 (range 26-60) years. Three patients had marked choroidal tumor regression after treatment with pemetrexed and cisplatin. In the literature reviews, there are only 12 patients (including our patients) received systemic chemotherapy alone instead of local therapy and eight (66.7 %) demonstrated choroidal tumor regression after treatment. CONCLUSIONS: Symptomatic choroidal metastasis from lung cancer is extremely rare. Our findings indicate that systemic chemotherapy with pemetrexed and cisplatin may be a good option for such patients. Further large-scale studies for the treatment of such patients are warranted. However, currently, radiotherapy is still the gold standard for such patients.