Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer

xlomafota13 shared this article with you from Inoreader Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer Via radioactive iodine Front Endocrinol (Lausanne). 2021 Jul 15;12:720723. doi: 10.3389/fendo.2021.720723. eCollection 2021. ABSTRACT Iodine-resistant cancers account for the vast majority of thyroid related mortality and, until recently, there were limited therapeutic options. However, over the last decade our understanding of the molecular foundation of thyroid function and carcinogenesis has driven the development of many novel therapeutics. These include FDA approved tyrosine kinase inhibitors and sm all molecular inhibitors of VEGFR, BRAF, MEK, NTRK and RET, which collectively have significantly changed the prognostic outlook for this patient population. Some therapeutics can re-sensitize de-differentiated cancers to iodine, allowing for radioactive iodine treatment and improved disease control. Remarkably, there is now an FDA approved treatment for BRAF-mutated patients with anaplastic thyroid cancer, previously considered invariably and rapidly fatal. The treatment landscape for iodine-resistant thyroid cancer is changing rapidly with many new targets, therapeutics, clinical trials, and approved treatments. We provide an up-to-date review of novel therapeutic options in the treatment of iodine-resistant thyroid cancer. PMID:34335481 | PMC:PMC8321684 | DOI:10.3389/fendo.2021.720723 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hyperthyroidism management during pregnancy and lactation (Review)

xlomafota13 shared this article with you from Inoreader Hyperthyroidism management during pregnancy and lactation (Review) Via radioactive iodine Exp Ther Med. 2021 Sep;22(3):960. doi: 10.3892/etm.2021.10392. Epub 2021 Jul 7. ABSTRACT Thyroid dysfunction is a significant public health issue, affecting 5-10 more women compared to men. The estimated incidence is up to 12% and only for women the treatment rises up to 4.3 billion dollars annually. Thyroid pathology can have a major impact on female fertility and it can only be detected when preconception tests are performed. Untreated or poorly treated hyperthyroidism in a mothe r can affect the fetal development and pregnancy outcome. Between 0.1 and 0.4% of the pregnancies are affected by clinical hyperthyroidism. Thyroid dysfunction is associated with higher rates of pregnancy loss. Hyperthyroidism can complicate fetal health problems intrauterinely and in the neonatal period. The TSH receptor is stimulated by TSH and HCG which has a similar structure. This can lead to gestational thyrotoxicosis. Hyperthyroidism can be treated with propylthiouracil or methimazole and in selected cases, surgical treatment or radioactive iodine can be chosen. In pregnancy, the most used treatment is represented by propylthiouracil which can be used from the first trimester. The aim of this review is to assess the current data regarding the impact of thyroid dysfunction on pregnancy and to synthesize the treatment options during pregnancy and lactation. PMID:34335902 | PMC:PMC8290437 | DOI:10.3892/etm.2021.10392 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ginkgo biloba extract protects human neuroblastoma SH-SY5Y cells against oxidative glutamate toxicity by activating redoxosome-p66Shc

xlomafota13 shared this article with you from Inoreader <em>Ginkgo biloba</em> extract protects human neuroblastoma SH-SY5Y cells against oxidative glutamate toxicity by activating redoxosome-p66Shc Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):951. doi: 10.3892/etm.2021.10383. Epub 2021 Jul 5. ABSTRACT Ginkgo biloba extract (GBE), a traditional Chinese herbal medicine component, is widely used to alleviate symptoms of neurodegenerative diseases. It has been confirmed that GBE exerts its pharmacological effect mainly due to its antioxidant activity; however, the molecular mechanism responsible for this effect remains unclear. The aim of the present study was to investigate the detailed mechanism of GBE, the main component of Gingko biloba dropping medicine, against oxidative glutamate toxicity in human neuroblastoma SH-SY5Y cells. The SH-SY5Y cells were untreated or pretreated with GBE followed by glutamate stimulation. Cell viability was assessed using an MTT assay. In addition, oxidative stress indexes, including intracellular ROS generation and NADPH oxidase and caspase activity, were also measured. The protein expression of key s ignaling factors involved in the redoxosome-p66Shc pathway was evaluated to elucidate the neuroprotective effect of GBE. The results showed that GBE treatment significantly attenuated the glutamate-induced cytotoxicity in SH-SY5Y cells by suppressing oxidative stress. A mechanical study revealed that redoxosome-p66Shc activation was associated with glutamate-induced cytotoxicity, which caused mitochondrial dysfunction and cell death. Interestingly, GBE treatment attenuated the activation of redoxosome-p66Shc in a dose-dependent manner, which suggested that the protective effect of GBE on SH-SY5Y cells against oxidative glutamate toxicity may be mediated by the modulation of redoxosome-p66Shc signaling. The current findings contribute to a better understanding of the therapeutic effect of GBE and indicate that redoxosome-p66Shc signaling might be a novel therapeutic target in the prevention and/or treatment of neurodegenerative diseases. PMID:34335893 | PMC:PMC8290427 | DOI:10.3892/etm.2021.10383 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Animal models of vertical bone augmentation (Review)

xlomafota13 shared this article with you from Inoreader Animal models of vertical bone augmentation (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):919. doi: 10.3892/etm.2021.10351. Epub 2021 Jun 30. ABSTRACT Vertical bone augmentation is an important challenge in dental implantology. Existing vertical bone augmentation techniques, along with bone grafting materials, have achieved certain clinical progress but continue to have numerous limitations. In order to evaluate the possibility of using biomaterials to develop bone substitutes, medical devices and/or new bone grafting techniques for vertical bone augmentation, it is essential to establish clinically relevant animal models to investigate their biocompatibility, mechanical properties, applicability and safety. The present review discusses recent animal experiments related to vertical bone augmentation. In addition, surgical protocols for establishing relevant preclinical models with various animal species were reviewed. The present study aims to provide guidance for selecting experimental animal m odels of vertical bone augmentation. PMID:34335880 | PMC:PMC8290405 | DOI:10.3892/etm.2021.10351 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Monaldi cavernostomy for lung aspergillosis: A case report

xlomafota13 shared this article with you from Inoreader Monaldi cavernostomy for lung aspergillosis: A case report Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):957. doi: 10.3892/etm.2021.10389. Epub 2021 Jul 6. ABSTRACT Pulmonary aspergillosis in patients with respiratory failure can severely affect the pulmonary functional status and may aggravate it through pulmonary suppuration, by recruitment of new parenchyma and hemoptysis, which can sometimes be massive, with lethal risk by flooding the bronchus. The treatment consists of a combination of medical therapy, surgery and interventional radiology. In small lesions, less than 2-3 cm, medical therapy methods may be sufficient; however, in invasive forms (larger than 3 cm) surgical resection is necessary. Surgical resection is the ideal treatment; nevertheless, when lung function does not allow it, action must be taken to eliminate the favorable conditions of the infection. In such cases, whenever the lung cavity is peripheral, a cavernostomy may be performed. Four cases of lung cavernous lesions colonized with asp ergillus, in which the need for a therapeutic gesture was imposed by repeated small to medium hemoptysis and by the progression of respiratory failure, were evaluated, one of which is presented in the current study. Cavernostomy closure can be realized either surgically with muscle flap or spontaneously by scarring, after closure of the bronchial fistulas by epithelization and granulation. There were no recurrences of hemoptysis or suppurative phenomena. There was one death, a patient with severe respiratory failure caused by superinfection with nonspecific germs. However, in the case presented in this study, the patient recovered following cavernostomy, which seems to be an effective and safe method for cases in which lung resection is not feasible. PMID:34335899 | PMC:PMC8290423 | DOI:10.3892/etm.2021.10389 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Application of propofol combined with sevoflurane anesthesia in staged hepatectomy liver detachment and portal vein ligation

xlomafota13 shared this article with you from Inoreader Application of propofol combined with sevoflurane anesthesia in staged hepatectomy liver detachment and portal vein ligation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):921. doi: 10.3892/etm.2021.10353. Epub 2021 Jun 30. ABSTRACT The aim of the present study was to investigate the application of propofol combined with sevoflurane anesthesia in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). A retrospective analysis of 40 patients with liver cancer who underwent ALPPS was performed. The study included 21 (control group) and 19 (observation group) patients who were administered propofol anesthesia and propofol in combination with sevoflurane anesthesia, respectively. Changes in liver function indicators, routine blood parameters and blood coagulation function, as well as cognitive function (mini-mental state examination) were recorded. The total bilirubin and direct bilirubin levels and the alanine aminotransferase (ALT) level after the first- and second-stage operation in the two groups was also higher than that prior to the first-stage operation (P<0.05), and the ALT level was significantly lower in the two groups after the second-stage operation compared with that prior to the second-stage operation (P<0.05). The AST level after the first- and second-stage operation was lower than that prior to the first- and second-stage operation, respectively (P<0.05). The white blood cell count after the second-stage operation was significantly lower compared with that prior to the second-stage operation (P<0.05). The plasma fibrinogen (FIB) level was higher after the first-stage operation compared with that prior to the first-stage operation (P<0.05). The prothrombin time in the two groups of patients was higher after the second-stage operation compared with that prior to the second-stage operation (P<0.05), whereas the FIB level was lower (P<0.05) and the international normalized ratio was not significantly different (P>0.05). The degree of cognitive decline prior to the first/second-stage operation, according to mini-mental state examination scores, was different from that after the first/second-stage operation (P<0.05). In conclusion, propofol combined with sevoflurane has a good application value in ALPPS. PMID:34335882 | PMC:PMC8290462 | DOI:10.3892/etm.2021.10353 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

FOXP3 facilitates the invasion and metastasis of non-small cell lung cancer cells through regulating VEGF, EMT and the Notch1/Hes1 pathway

xlomafota13 shared this article with you from Inoreader FOXP3 facilitates the invasion and metastasis of non-small cell lung cancer cells through regulating VEGF, EMT and the Notch1/Hes1 pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):958. doi: 10.3892/etm.2021.10390. Epub 2021 Jul 6. ABSTRACT Forkhead box P3 (FOXP3) is a specific marker of regulatory T cells (Tregs) that is also expressed in tumour cells. Previous studies have revealed that FOXP3 can promote metastasis in several types of cancer, including non-small cell lung cancer (NSCLC); however, the underlying mechanism of FOXP3 remains unclear. The aim of the present study was to investigate the effect of FOXP3 on vascular endothelial growth factor (VEGF), epithelial-to-mesenchymal transition (EMT) and the Notch1/Hes1 pathway in NSCLC. After FOXP3 small interfering RNA (siRNAs) were transfected into A549 cells, the expression of FOXP3 mRNA and protein was determined by reverse transcription-quantitative PCR and western blotting. Cell migration and invasion were analyzed by Transwell assays. The concentrations of matrix metalloproteinase (MMP)-2, MMP-9 and VEGF in the cell supernat ant were evaluated by ELISA. The expression of relevant proteins involved in EMT and Notch1/Hes1 pathway were assessed via western blotting. Additionally, the expression of FOXP3, CD31 and E-cadherin was detected by immunohistochemical (IHC) staining of 55 human NSCLC tissue samples. The results demonstrated that FOXP3 knockdown significantly inhibited the cell migratory and invasive abilities, decreased the concentrations of MMP-2, MMP-9 and VEGF, downregulated the protein expression of vimentin, N-cadherin, Notch1 and Hes family BHLH transcription factor 1 (Hes1), and upregulated the protein expression of E-cadherin. Furthermore, FOXP3 expression was positively associated with CD31+ vascular endothelial cells and negatively correlated with E-cadherin in NSCLC tissues. In addition, the Notch1/Hes1 pathway inhibitor DAPT significantly downregulated the expression of FOXP3 in a dose-dependent manner. Taken together, these findings demonstrated that FOXP3 may facilitate the invasive and migratory abilities of NSCLC cells via regulating the angiogenic factor VEGF, the EMT and the Notch1/Hes1 pathway. PMID:34335900 | PMC:PMC8290412 | DOI:10.3892/etm.2021.10390 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Combination treatment with cisplatin, paclitaxel and olaparib has synergistic and dose reduction potential in ovarian cancer cells

xlomafota13 shared this article with you from Inoreader Combination treatment with cisplatin, paclitaxel and olaparib has synergistic and dose reduction potential in ovarian cancer cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):935. doi: 10.3892/etm.2021.10367. Epub 2021 Jul 1. ABSTRACT Ovarian cancer is the most lethal type of gynecological cancer. Due to its high heterogeneity and complicated pathological mechanisms, the 5-year survival rate of patients with ovarian cancer is <40%. Tumor cytoreductive surgery and systemic chemotherapy of platinum combined with paclitaxel are currently considered the gold standard for the treatment of ovarian cancer, and chemotherapy resistance has become a key constraint in improving the cure rate of ovarian cancer. Therefore, it is important to identify novel treatment methods and strategies for ovarian cancer. Targeted drugs can not only be used in combination with chemotherapy, but also act as maintenance therapy to promote patient survival time. PARP inhibitor is a novel type of ovarian cancer treatment targeted drug, which can induce an anticancer effect by inhibiting DNA damage and repa ir of ovarian cancer cells. The present study investigated the different effects of olaparib, cisplatin and paclitaxel in several dosages by single use and combinations on the proliferation of different human ovarian cancer cell lines, in order to verify the synergistic effects of the combinations of the three anticancer agents in pairs. The proliferation inhibitory rate of the cell lines was determined using a Cell Counting Kit-8 assay, while the combination index (CI) value of the combination of three agents in pairs was analyzed using Compusyn software. The proliferation was observed using a crystal violet assay, and the apoptosis ratio was measured via flow cytometry. The results of the present study revealed that the combination of cisplatin with olaparib group had a higher inhibition effect than each single group and had a higher dose-reduction index of >1 than the other two combinations at all concentrations in A2780 and OVCAR-3 cell lines. The difference in proliferation inhibition and induced apoptosis rate of A2780 cell lines was significant in the combination of cisplatin with olaparib group and the control group (P<0.01) at 0.25x IC50. For the OVCAR-3 cell line, the difference was also significant between two groups (P<0.05). The CI values in the A2780 cell line revealed significant differences between the low-dose group (0.0625x, 0.125x and 0.25x IC50) and the high-dose group (0.5x, 1.0x and 2.0x IC50) for the group that received the combination of cisplatin with olaparib (P<0.05). The present study highlighted that the group receiving a combination of cisplatin with olaparib exhibited the most significant synergistic effects among the three combinations, particularly at low doses. PMID:34335884 | PMC:PMC8290430 | DOI:10.3892/etm.2021.10367 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Attitude of the surgical approach in hyperparathyroidism: A retrospective study

xlomafota13 shared this article with you from Inoreader Attitude of the surgical approach in hyperparathyroidism: A retrospective study Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):959. doi: 10.3892/etm.2021.10391. Epub 2021 Jul 7. ABSTRACT The present study constitutes a retrospective study for patients with hyperparathyroidism surgically operated on at the Department of Thoracic Surgery of the Central Military Emergency University Hospital 'Dr. Carol Davila', Bucharest, Romania (SUUMC), over a period of 6 years. The study aimed to elucidate the diagnostic and surgical attitude for an effective treatment, practiced at SUUMC, Romania. The study group included 55 patients: 41 women and 14 men, diagnosed at the endocrinology department, who underwent various personalized surgeries (Kocher modified incision) for typical and ectopic locations of parathyroid pseudotumor formations (hyperplasia and parathyroid adenoma), to cure the disease. The recommended protocol was followed by immediate and 30-day postoperative evaluation which showed normalization of the blood tests, and improved clini cal and imaging anomalies. In conclusion, the thoracic surgeon has the necessary knowledge to perform surgery at the cervical, thoracic-cervical and mediastinal levels. Postoperative, the results of laboratory tests for calcium (Ca) and parathyroid hormone (PTH) gradually returned to normal, as can be seen from the statistical study. PMID:34335901 | PMC:PMC8290464 | DOI:10.3892/etm.2021.10391 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-146a overexpression alleviates intestinal ischemia/reperfusion-induced acute lung injury in mice

xlomafota13 shared this article with you from Inoreader MicroRNA-146a overexpression alleviates intestinal ischemia/reperfusion-induced acute lung injury in mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):937. doi: 10.3892/etm.2021.10369. Epub 2021 Jul 1. ABSTRACT Previous studies have shown that microRNAs (miRs), such as miR-146a play an important role in the pathogenesis of intestinal ischemia/reperfusion (I/R)-induced injury; however, the role of miR-146a in intestinal I/R-induced acute lung injury has not been elucidated. An intestinal I/R-induced injury mouse model was established in the present study by clamping the superior mesenteric artery and expression levels of miR-146a in intestinal and lung tissue samples were evaluated using reverse transcription-quantitative PCR (RT-qPCR). Intestinal and lung histopathological characteristics in mice with intestinal I/R-induced injury were assessed by hematoxylin and eosin staining, and mRNA and protein expression levels in intestinal and lung tissue samples were evaluated using RT-qPCR and western blotting, respectively. miR-146a expression was significantly downregulated in the intestinal and lung tissue samples of mice with intestinal I/R-induced injury. Intestinal I/R injury-induced histopathological changes in the lung and intestines, and pulmonary edema in mice transduced with an adenoviral miR-146a-overexpression vector (the miR-146a overexpression group) were alleviated. mRNA expression levels of TNF-α, IL-1β, IFN-γ and TGF-β1, and protein expression levels of TNF receptor-associated factor 6, phosphorylated-p65 NF-κB, cleaved caspase-3 and cleaved caspase-9 in lung and intestinal tissue samples were downregulated in I/R-miR-146a-overexpressing mice, compared with those from the I/R-negative control group. Thus, the present study identified that pre-treatment with the miR-146a overexpression vector alleviated intestinal I/R-induced acute lung injury in mice. PMID:34335886 | PMC:PMC8290461 | DOI:10.3892/etm.2021.10369 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.