The Interplay of Lung Cancer, COVID-19, and Vaccines Trivanović, Dragan; Peršurić, Željka; Agaj, Andrea ...
International journal of molecular sciences,
2022-Dec-01, 2022-12-01, 20221201, Letnik:
23, Številka:
23
Journal Article
Recenzirano
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Patients with cancer are more susceptible to a higher risk of coronavirus infection and its severe complications than the general population. In addition, these patients were not included in the ...pivotal clinical trials for COVID-19 vaccines. Therefore, considerable uncertainty remains regarding the management of cancer patients during the COVID-19 pandemic and the safety of COVID-19 vaccinations in cancer patients. In this review, we summarize the current knowledge generated from the beginning of the COVID-19 pandemic on the vulnerability of cancer patients to the coronavirus disease, as well as the effectiveness of COVID-19 vaccines in this population. We also discuss the available data on the effects of anticancer treatment with immune checkpoint inhibitors on the immune responses to SARS-CoV-2 in cancer patients. Special attention in this review will be given to patients with lung cancer, as such patients are at an increased risk for severe effects from COVID-19.
C-reactive protein (CRP) and leukocyte count are standard tools for recognising inflammation in COPD patients. This study aimed to find if there is a pattern in monocyte related haematological ...indices - monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR) - which could be helpful in differentiating COPD patients in need for hospitalization due to acute exacerbation of COPD or differentiating frequent COPD exacerbators from non-frequent COPD exacerbators. The study included 119 patients with COPD and 35 control subjects, recruited at the Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Croatia. Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. The COPD patients were divided into three groups – frequent exacerbators (FE), non-frequent exacerbators (NFE), patients hospitalized for acute COPD exacerbations (HAE) and the control group were healthy smokers (HS). A statistically significant difference was found in the values of MNR while comparing these groups of patients: FE vs HAE (p<0.000), NFE vs HAE (p<0.000) and HS vs HAE (p<0.001); and for the values of MLR: FE vs HAE (p<0.022), NFE vs HAE (p<0.000) and HS vs HAE (p<0.000). As MLR and MNR have shown the statistical difference comparing the group of HAE to NFE, FE and HS, MLR and MNR could be valuable and available markers of acute COPD exacerbations and need for hospitalization.
Primary sarcoma of the lung is a very rare malignant tumor accounting for less than 0.5% of all lung tumors and presenting diagnostic and treatment challenge. We describe a case of a patient ...diagnosed with primary lung undifferentiated pleomorphic sarcoma developing subsequent peritoneal and small bowel metastases, which stand for highly unusual disease presentation.
A 57-year-old male presented with extensive partially necrotic tumor in the left upper lobe (LUL) of the lung that involved LUL bronchus and extended to the visceral pleura. There was no evidence of nodal or visceral dissemination. After initial presentation, the patient was admitted to the hospital's pulmonology department for further workup. The most likely diagnosis based on biopsy specimen was poorly differentiated sarcoma. Left pneumonectomy with mediastinal lymph node dissection was performed. The final pathohistological diagnosis (PHD) was undifferentiated pleomorphic sarcoma (UPS). Three months after lung surgery, a follow-up CT scan was done which showed a 60-mm obstructive metastatic intraabdominal lesion with small bowel infiltration and further separate peritoneal deposits. Unfortunately, an urgent surgery had to be performed as the patient developed signs of acute abdomen due to bowel perforation. Only 2 months later, the patient passed away at home.
Treatment options of UPS are based on algorithms used in treatment of extremity lesions with well-established role of surgery. However, the role of perioperative chemotherapy remains equivocal with no strong evidence-based data due to the rarity of the disease. Small bowel is an unexpected metastatic site, but of significant clinical relevance.
Malignant pleural mesothelioma (MPM) has a very poor prognosis. Although clinical stage is currently the only reliable prognostic factor, histologic subtyping reportedly also affects prognosis. Some ...studies propose reclassification of pleomorphic epithelioid as biphasic or sarcomatoid MPM. This study assessed prognostic significance and interobserver agreement in MPM subtyping of small biopsy specimens. We analyzed biopsy specimens, and clinical and survival data from records of 108 patients who were diagnosed between 2000 and 2010 at the Institute of Pathology University of Zagreb School of Medicine, of whom 98 had epithelioid MPM, six biphasic MPM, and four sarcomatoid MPM. Among epithelioid subtypes, 44 (44.9 %) were solid, 19 (19.4 %) tubulopapillary, 18 (18.4 %) acinar, six (6.1 %) adenomatoid, five (5.1 %) pleomorphic, four (4.1 %) trabecular, and two (2.0 %) micropapillary subtype. Interobserver reliability for histological diagnosis was found to be
κ
= 0.72 (
P
< 0.001). Median overall survival for epithelioid MPM was 10.5 months with an interquartile range (IQR) of 5.8–28.0 months but significantly shorter for the pleomorphic subtype (3 IQR 3.0–8.0 months;
P
= 0.034), but not significantly different from biphasic (6.5 IQR 3.5–15.3 months) and sarcomatoid mesothelioma (4.0 IQR 1.3–6.8 months;
P
= 0.270). We found strong reproducibility of MPM subtyping with good interobserver agreement. Furthermore, our results indicate that pleomorphic subtype to be a predictor of poor prognosis and support classifying it with sarcomatoid or biphasic MPM, as patients with the pleomorphic, biphasic, or sarcomatoid subtype show similarly poor overall survival.
Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro ...kinase assays. Due to frequent development of drug resistance, however, there is a need to identify more diverse compounds that inhibit mutated but not wild-type RTKs. Here, we describe MaMTH-DS (mammalian membrane two-hybrid drug screening), a live-cell platform for high-throughput identification of small molecules targeting functional protein-protein interactions of RTKs. We applied MaMTH-DS to an oncogenic epidermal growth factor receptor (EGFR) mutant resistant to the latest generation of clinically approved tyrosine kinase inhibitors (TKIs). We identified four mutant-specific compounds, including two that would not have been detected by conventional in vitro kinase assays. One of these targets mutant EGFR via a new mechanism of action, distinct from classical TKI inhibition. Our results demonstrate how MaMTH-DS is a powerful complement to traditional drug screening approaches.
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still ...diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the “one-fits-all” paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.
Summary
Objective
Obstructive sleep apnea (OSA) is a common medical problem with numerous comorbidities and high costs. Since the introduction of the Epworth sleepiness scale (ESS), excessive daytime ...sleepiness (EDS) has been considered the most common and prominent symptom of OSA. Aim of this study was to re-evaluate the ESS for detection of OSA in a population at risk compared to the gold standard overnight polysomnography (PSG).
Methods
A total of 266 patients (mean age 57.9 ± 11.6 years; 189 men and 77 women), referred to our sleep laboratory for probable OSA, were given ESS followed by an overnight PSG. The ESS values were compared to PSG apnea hypopnea index (AHI) with sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) calculated for ESS. The positive cut-off value for ESS was ≥ 10 and for AHI ≥ 5.
Results
Only 92 (34.6%) subjects had a positive ESS. An OSA was diagnosed by PSG in 213 (80.1%) subjects: 46 having mild, 37 moderate and 130 severe apnea. Most subjects with positive ESS (88.0%) were found to have OSA but most subjects with a negative ESS (75.9%) were also positive for OSA (42% with AHI ≥ 30). The area under the receiver operating characteristic (ROC) curve for ESS was 0.60 (95% confidence interval, CI 0.54–0.66;
p
= 0.020) with SE 38.0%, SP 79.3%, PPV 88.0%, NPV 24.1% and DA 46.2%.
Conclusion
It was found that excessive daytime sleepiness, measured by ESS, is not a valuable screening tool for OSA, especially when the test is negative. Other screening tests that involve additional parameters, beside daytime sleepiness alone, should be considered.
Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the ...disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a
-value < 3.3 × 10
were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (
) to be associated with the COPD risk and two with the LC risk (
), with statistical significance. We also identified two SNPs located in the
gene associated with LC (rs2386841;
= 1.86 × 10
) and COPD (rs11256442;
= 9.79 × 10
) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.
BackgroundThe most effective method and length of time for administering adjuvant immunotherapy after surgery for non-small cell lung cancer (NSCLC) are still unknown. Various clinical trials have ...utilized diverse strategies for adjuvant treatment. In this case, we explore the potential benefits of neoadjuvant immunotherapy combined with chemotherapy in managing locally advanced lung squamous carcinoma, which often poses challenges for treatment. This multimodal approach aims to downstage tumors and optimize surgical outcomes.Case DescriptionFollowing a diagnosis of stage IIIB lung cancer, the patient underwent three cycles of neoadjuvant therapy using sintilimab, Abraxane, and Lobaplatin, resulting in a significant 45% reduction in tumor size. Subsequently, a right lower lobe lobectomy and systematic lymphadenectomy were performed using a uniportal video-assisted thoracic surgery (VATS) approach. Postoperative analysis revealed negative lymph nodes, with only a 5-mm residual tumor in the tumor bed, downstaging the cancer to IA1. Remarkably, the patient experienced a smooth recovery without any postoperative complications. One cycle of adjuvant therapy was administered following the operation to further support the patient's recovery and minimize the risk of disease recurrence. This comprehensive treatment approach underscores the importance of neoadjuvant therapy in optimizing surgical outcomes and improving long-term prognosis for patients with locally advanced lung cancer.ConclusionsFor patients with stage III locally advanced lung squamous carcinoma, the combination of Sintilimab and Platinum-based drugs can be used as a neoadjuvant therapy which can reduce the difficulty of the operation.
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