Immunotherapeutics and other anticancer agents in the management of advanced gastric cancer

Advanced gastric cancer (AGC) is characterized by high mortality. The survival is estimated as 14.2 months. The treat­ment of choice in the early stages of GC is surgery. Due to high potential of malignancy, postoperative chemotherapy is usually administered. Novel methods of treatment involve immunotherapeutic agents (IA). The new therapies seem to be a hopeful perspective for patients with advanced GC. In this review, we present the outcomes of clinical trials in GC treatment with IA and their mechanisms of action. Furthermore, we present the benefits and shortcomings of immunotherapy and describe potential directions for future research

Immunotherapeutics and other anticancer agents in the management of advanced gastric cancer

Advanced gastric cancer (AGC) is characterized by high mortality. The survival is estimated as 14.2 months. The treat­ment of choice in the early stages of GC is surgery. Due to high potential of malignancy, postoperative chemotherapy is usually administered. Novel methods of treatment involve immunotherapeutic agents (IA). The new therapies seem to be a hopeful perspective for patients with advanced GC. In this review, we present the outcomes of clinical trials in GC treatment with IA and their mechanisms of action. Furthermore, we present the benefits and shortcomings of immunotherapy and describe potential directions for future research

Leiomyosarcoma in adrenal gland

Not required for Clinical Vignette

Small cell carcinoma with neuroendocrine differentiation of subglottic larynx- a case report

Small cell cancer (SCC) is a neuroendocrine neoplasm, which is most frequently found in the lungs. Extrapulmonary location of SCC is rare and may involve 2.5-5% of SCCs. We present a case of a 31-year-old male patient with an extremely uncommon subglottic SCC. The patient was qualified for a radical sequential chemoradiotherapy. After treatment, patient’s condition suggested complete remission. Recurrence was detected one year later, and the disease rapidly progressed, despite a second line chemotherapy. The patient died 29 months after initial diagnosis. This case aims to raise awareness on the aggressive laryngeal SCC and its good response to first line chemotherapy composed of cisplatin and etoposide, followed by radiotherapy

SARS-CoV-2 and lung transplantation. What do we know?

Introduction: In 2019, new Coronavirus (SARS-CoV-2) has spread around the globe. The virus can replicatein the cells of the lower respiratory tract, causing pneumonia, oedema and hypoxia. In some patients, thedisease will progress to acute respiratory distress syndrome (ARDS) which is a life-threatening condition.Lung transplantation (LuTx) might be the only rescue therapy for severe respiratory failure. Additionally,little is known about the impact of SARS-CoV-2 on lung transplant recipients. The purpose of this systematicreview is to present current knowledge about lung transplantation as a treatment method for ARDSassociated with COVID-19 infection and to summarize information regarding the management of COVIDinfection in lung transplant recipients. Materials and methods: Literature search through different databases was conducted. Only case report and case series were included. Results: Out of 525 initial results, 16 studies were included in this systematic review. 7 articles presentedpatients with LuTx as a treatment option for ARDS and 9 presented management of lung recipients infectedwith COVID-19. A total of 37 patients were included in this systematic review. Discussion: The course of reviewed patients with SARS-CoV-2 infection was similar and lung transplantationshould be considered as a treatment of last chance when extracorporeal life support cannot be withdrawn.Further research is still required to assess the impact of new coronavirus on graft function in lung transplantrecipients. Currently, the treatment strategy involves immunosuppression modification and supplementaloxygen therapy. However, some patients do not present clinical symptoms

The Potential Role of Connexins in the Pathogenesis of Atherosclerosis

Connexins (Cx) are members of a protein family which enable extracellular and intercellular communication through hemichannels and gap junctions (GJ), respectively. Cx take part in transporting important cell–cell messengers such as 3′,5′-cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP), and inositol 1,4,5-trisphosphate (IP3), among others. Therefore, they play a significant role in regulating cell homeostasis, proliferation, and differentiation. Alterations in Cx distribution, degradation, and post-translational modifications have been correlated with cancers, as well as cardiovascular and neurological diseases. Depending on the isoform, Cx have been shown either to promote or suppress the development of atherosclerosis, a progressive inflammatory disease affecting large and medium-sized arteries. Cx might contribute to the progression of the disease by enhancing endothelial dysfunction, monocyte recruitment, vascular smooth muscle cell (VSMC) activation, or by inhibiting VSMC autophagy. Inhibition or modulation of the expression of specific isoforms could suppress atherosclerotic plaque formation and diminish pro-inflammatory conditions. A better understanding of the complexity of atherosclerosis pathophysiology linked with Cx could result in developing novel therapeutic strategies. This review aims to present the role of Cx in the pathogenesis of atherosclerosis and discusses whether they can become novel therapeutic targets

How to Restore Oxidative Balance That Was Disrupted by SARS-CoV-2 Infection

Coronavirus 2019 disease (COVID-19) is caused by different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December of 2019. COVID-19 pathogenesis is complex and involves a dysregulated renin angiotensin system. Severe courses of the disease are associated with a dysregulated immunological response known as cytokine storm. Many scientists have demonstrated that SARS-CoV-2 impacts oxidative homeostasis and stimulates the production of reactive oxygen species (ROS). In addition, the virus inhibits glutathione (GSH) and nuclear factor erythroid 2-related factor 2 (NRF2)—a major antioxidant which induces expression of protective proteins and prevents ROS damage. Furthermore, the virus stimulates NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes which play a significant role in inducing a cytokine storm. A variety of agents with antioxidant properties have shown beneficial effects in experimental and clinical studies of COVID-19. This review aims to present mechanisms of oxidative stress induced by SARS-CoV-2 and to discuss whether antioxidative drugs can counteract detrimental outcomes of a cytokine storm

The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Rheumatoid Arthritis and Osteoarthritis

Cells can communicate with each other through extracellular vesicles (EVs), which are membrane-bound structures that transport proteins, lipids and nucleic acids. These structures have been found to mediate cellular differentiation and proliferation apoptosis, as well as inflammatory responses and senescence, among others. The cargo of these vesicles may include immunomodulatory molecules, which can then contribute to the pathogenesis of various diseases. By contrast, EVs secreted by mesenchymal stem cells (MSCs) have shown important immunosuppressive and regenerative properties. Moreover, EVs can be modified and used as drug carriers to precisely deliver therapeutic agents. In this review, we aim to summarize the current evidence on the roles of EVs in the progression and treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), which are important and prevalent joint diseases with a significant global burden

The Potential Role of Connexins in the Pathogenesis of Atherosclerosis

Connexins (Cx) are members of a protein family which enable extracellular and intercellular communication through hemichannels and gap junctions (GJ), respectively. Cx take part in transporting important cell–cell messengers such as 3′,5′-cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP), and inositol 1,4,5-trisphosphate (IP3), among others. Therefore, they play a significant role in regulating cell homeostasis, proliferation, and differentiation. Alterations in Cx distribution, degradation, and post-translational modifications have been correlated with cancers, as well as cardiovascular and neurological diseases. Depending on the isoform, Cx have been shown either to promote or suppress the development of atherosclerosis, a progressive inflammatory disease affecting large and medium-sized arteries. Cx might contribute to the progression of the disease by enhancing endothelial dysfunction, monocyte recruitment, vascular smooth muscle cell (VSMC) activation, or by inhibiting VSMC autophagy. Inhibition or modulation of the expression of specific isoforms could suppress atherosclerotic plaque formation and diminish pro-inflammatory conditions. A better understanding of the complexity of atherosclerosis pathophysiology linked with Cx could result in developing novel therapeutic strategies. This review aims to present the role of Cx in the pathogenesis of atherosclerosis and discusses whether they can become novel therapeutic targets

Arterial sleeve lobectomy for lung cancer invading chest wall

Lung cancer is a leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is a predominant subtype and treatment may include immunotherapy, radiotherapy, chemotherapy, and surgery. Tumors of bigger size infiltrating large bronchi and vessels require more invasive resection such as pneumonectomy. To save lung parenchyma, sleeve lobectomy can be performed in certain patients. We report the case of a patient with NSCLC infiltrating the chest wall who underwent arterial sleeve lobectomy with rib resection. Furthermore, we discuss other surgical treatment strategies. A 58-year-old female patient was admitted to the hospital in 2020 with pain in her left posterolateral chest. Radiological imaging revealed a tumor (5.0×3.5×4.8 cm) in the top of the left lung, infiltrating pulmonary artery and ribs. Therefore, left upper sleeve lobectomy together with resection of rib blocks II to V was performed. The surgery was uncomplicated, but a few weeks postoperatively, the patient experienced repeated episodes of consciousness disturbances. Contrast CT revealed a cerebral malformation in the patient who died 3.5 months after surgery. Sleeve lobectomy can be safely performed in patients with lung tumors infiltrating larger bronchi and vessels who would not tolerate pneumonectomy