ritonavir and Carcinoma--Squamous-Cell

We present three patients affected by pulmonary squamous cell carcinoma, metastatic esophageal cancer and advanced non-Hodgkin lymphoma, who incurred in coronavirus 2019 (COVID-19) infection during the early phase of epidemic wave in Italy. All patients presented with fever. Social contact with subject positive for COVID-19 was declared in only one of the three cases. In all cases, laboratory findings showed lymphopenia and elevated C-reactive protein (CRP). Chest x-ray and computed tomography showed bilateral ground-glass opacities, shadowing, interstitial abnormalities, and "crazy paving" pattern which evolved with superimposition of consolidations in one patient. All patients received antiviral therapy based on ritonavir and lopinavir, associated with hydroxychloroquine. Despite treatment, two patients with advanced cancers died after 39 and 17 days of hospitalization, while the patient with lung cancer was dismissed at home, in good conditions.

Topics: Aged; Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Carcinoma, Squamous Cell; Coronavirus Infections; COVID-19; Disease Outbreaks; Drug Therapy, Combination; Esophageal Neoplasms; Fatal Outcome; Humans; Hydroxychloroquine; Italy; Lopinavir; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

The study focused on identifying the mechanisms or drugs that might sensitize resistant KBV20C human oral squamous carcinoma cells overexpressing P-glycoprotein (P-gp) to antimitotic drug treatment.. Five HIV protease inhibitors (atazanavir, nelfinavir, darunavir, lopinavir, and ritonavir) were tested to identify drugs that could be used at a relatively low dose for sensitizing antimitotic drug-resistant KBV20C cells. Fluorescence-activated cell sorting, annexin V analyses, and rhodamine uptake tests were performed to further investigate the mechanism of action.. Co-treatment with nelfinavir or lopinavir had a high sensitizing effect on vincristine-treated KBV20C cells. Nelfinavir and lopinavir reduced cell viability, increased G. Highly antimitotic drug-resistant KBV20C cells can be sensitized by co-treatment with the repositioned HIV protease inhibitors nelfinavir and lopinavir. In particular, the sensitizing effect of co-treatment with nelfinavir on antimitotic drug-resistant cancer cells was found to be strong and independent of P-gp-inhibitory activity. As P-gp inhibition can be toxic to normal cells, selecting nelfinavir may be safer for normal cells in patients with drug-resistant cancer.

Topics: Antimitotic Agents; Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Squamous Cell; Cell Line, Tumor; Drug Resistance, Neoplasm; Drug Synergism; Fluphenazine; Furans; HIV Protease Inhibitors; Humans; Ketones; Lopinavir; Mouth Neoplasms; Nelfinavir; Ritonavir; Vincristine

Topics: Acute Disease; Adult; Alanine Transaminase; Anti-Inflammatory Agents; Anus Neoplasms; Aryl Hydrocarbon Hydroxylases; Budesonide; Carcinoma, Squamous Cell; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Middle Aged; Oxidoreductases, N-Demethylating; Ritonavir