The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting ...RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to-mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth. RAGE knockdown with multiple independent shRNAs in breast cancer cells led to decreased transwell invasion and soft agar colony formation, without affecting proliferation. In vivo, targeting RAGE shRNA knockdown in human and mouse breast cancer cells, decreased orthotopic tumor growth, reduced tumor angiogenesis and recruitment of inflammatory cells, and markedly decreased metastasis to the lung and liver in multiple xenograft and syngeneic mouse models. To test the non-tumor cell microenvironment role of RAGE, we performed syngeneic studies with orthotopically injected breast cancer cells in wild-type and RAGE-knockout C57BL6 mice. RAGE-knockout mice displayed striking impairment of tumor cell growth compared with wild-type mice, along with decreased mitogen-activated protein kinase signaling, tumor angiogenesis and inflammatory cell recruitment. To test the combined inhibition of RAGE in both tumor cell-intrinsic and non-tumor cells of the microenvironment, we performed in vivo treatment of xenografted tumors with FPS-ZM1 (1 mg/kg, two times per week). Compared with vehicle, FPS-ZM1 inhibited primary tumor growth, inhibited tumor angiogenesis and inflammatory cell recruitment and, most importantly, prevented metastasis to the lung and liver. These data demonstrate that RAGE drives tumor progression and metastasis through distinct tumor cell-intrinsic and -extrinsic mechanisms, and may represent a novel and therapeutically viable approach for treating metastatic cancers.
Patients who have undergone a lung resection owing to primary spontaneous pneumothorax (PSP) may develop prolonged air leak (PAL) during the postoperative period. The present study investigates ...potential risk factors associated with postoperative PAL in patients who were operated on for PSP.
Patients who underwent operations for PSP between January 2004 and November 2017 were investigated retrospectively. Patients who developed postoperative PAL constituted Group 1, and patients without PAL formed Group 2. A comparison of the two groups was made to identify potential risk factors for the development of prolonged air leak.
Of the total 79 patients who underwent operations, 18 (22.78%) developed prolonged air leak. All of the patients in Group 1 were male, and the mean age of this group was 23.72 ± 5.76 (18-36) years. Of the patients in Group 2, 51 (83.61%) were male and 10 (16.39%) were female, and the mean age of this group was 25.81 ± 5.91 (17-39) years. There was no statistically significant difference noted between the two groups regarding the investigated factors including age, gender, the total number of previous episodes, number of ipsilateral episodes, number of contralateral episodes, the preferred treatment method for the last episode, smoking status, computerized tomography findings, or the presence of a preoperative air leak.
PAL is the most common complication associated with PSP surgeries. Although several factors may affect PAL development, no definite conclusion could be drawn concerning the investigated risk factors. We believe that similar studies may contribute to the care of this rare patient population.
The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel ...coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood.
To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS.
The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics.
COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0–2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7–1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation.
There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.
Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection described in Asia, Africa and Europe. Humans become infected through the bites of ticks, by contact with a patient with CCHF during ...the acute phase of infection, or by contact with blood or tissues from viremic livestock. The occurrence of CCHF closely approximates the known world distribution of Hyalomma spp. ticks. The novel studies of phylogenetic analyses reveal the interesting relations between the strains from distant outbreaks. The clinical features show common dramatic progress characterized by hemorrhage, myalgia, and fever. Besides the direct infection of endothelium, indirect damage by viral or virus mediated host-derived soluble factors that cause endothelial activations and dysfunction occur. In diagnosis, enzyme linked immunoassay and real-time reverse transcription-polymerase chain reaction are used. Early diagnosis is critical for the patient and potential nosocomial infections. Supportive therapy is the essential part of the case management. Ribavirin was suggested as an effective drug in recent studies, and it was found to be beneficial. The health care workers are under serious risk of transmission of the infection, particularly during the follow-up of the patient, with hemorrhages from the nose, mouth, gums, vagina, and injection sites.
Crimean-Congo hemorrhagic fever (CCHF) has the most extensive geographic range of the medically significant tick-borne viruses, occurring from western China across southern Asia to eastern Europe and ...South Africa. The causative agent is a negative-sense, single-stranded RNA virus in the genus
Nairovirus, family Bunyaviridae. In published reports, the case fatality rate has generally ranged from 10% to 50%. Sporadic cases and outbreaks of the disease have increased during the past decade across the endemic region. CCHF was first diagnosed in Turkey in 2002, but since then more than 1100 cases have been confirmed by IgM serology or RT-PCR, with a fatality rate of just over 5%. Simple methods are available for the
in vitro evaluation of antiviral drugs, but because CCHF virus does not cause disease in its reservoir species or in laboratory animals other than suckling mice, methods are lacking for
in vivo efficacy testing. Intravenous or oral ribavirin has been used in several countries to treat the disease for more than 20 years. Evidence of its efficacy is limited to observational studies, and placebo-controlled trials may be impossible to perform for ethical reasons. However, careful analysis of properly stratified observational studies can be used to assess the effects of treatment. This article reviews current approaches to the treatment of CCHF, focusing on the use of ribavirin and hematological support, and discusses prospects for future research.
Relationships among the main food safety concerns and food consumption habits of 600 consumers living in Manisa City center, Turkey were evaluated. Respondents were interviewed face-to-face by a ...structured questionnaire. Sixty six questions under different groups (demographics of respondents, food safety perceptions, and awareness of food-borne illnesses, contaminants of foods and hazards, sources of food safety information, confidence in food safety authorities, food handling and safety practices at homes) were asked in the interview. Data obtained from the study indicated the need for much more consumer education regarding safe food handling practices in the domestic environment. Food handling practices and food safety are of public concern, and action is required to prevent the food-borne illnesses. It was seen that, TV and radio programmes are important media for sharing the knowledge of food safety with consumers.
► We determined the awareness of the Turkish consumers in terms of food safety. ► Study indicated the need for more education regarding safe food handling practices. ► This subject of public concern, and action is required to prevent food-borne illnesses. ► TV and radio are important media for sharing the knowledge of food safety. ► Government publications are more trusted by the consumers.
Several global efforts are underway to develop COVID-19 vaccines, and interim analyses from phase 3 clinical testing have been announced by nine organisations: Pfizer, the Gamaleya Research Institute ...of Epidemiology and Microbiology, Moderna, AstraZeneca, Sinopharm Group, Sinovac Biotech, Johnson & Johnson, Novavax, and CanSino Biologics. The US programme known as Operation Warp Speed provided US$18 billion in funding for development of vaccines that were intended for US populations. Depending on safety and efficacy, vaccines can become available through mechanisms for emergency use, expanded access with informed consent, or full licensure. An important question is: how will these Operation Warp Speed vaccines be used for COVID-19 prevention in global health settings? We address some key questions that arise in the transition from US to global vaccine prevention efforts and from ethical and logistical issues to those that are relevant to global vaccine security, justice, equity, and diplomacy.
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