Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Τετάρτη 9 Μαρτίου 2022

Robotic‐Assisted Partial Cystectomy for Muscle Invasive Bladder Cancer: Contemporary Experience

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Abstract

Objective

To report our contemporary experience with robotic-assisted partial cystectomy (RAPC) for muscle invasive bladder cancer

Methods

This is a retrospective review of patients who underwent robotic-assisted partial cystectomy with us between 2013 and 2020 and provided ≥ 12 months of follow up.

Results

and limitations: The median operative time for our 35 patients was 190 min (Interquartile range (IQR) 155–280). Four patients developed grade 3 or higher complications (ileus, pneumonia, and urethral stricture). At 12 months follow-up, the median IPSS score was 10 (IQR 7-11), and recurrence happened in seven patients (recurrence-free survival 80%). Five of the patients who developed recurrence died because of their disease, and two other patients died of causes unrelated to their cancer.

Conclusions

We describe our technique, functional outcomes, and short-term follow up results in highly selected patients with muscle-invasive bladder cancer treated with RAPC.

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Radioactive iodine and female fertility

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Sci Rep. 2022 Mar 8;12(1):3704. doi: 10.1038/s41598-022-07592-8.

ABSTRACT

Radioactive iodine (I131) is used after surgery in the treatment of Differentiated Thyroid Carcinoma (DTC). There is no solid evidence about the potential deleterious effect of I131 on women fertility. The objective of this study is to assess the impact that I131 may have on fertility in women. All women followed by DTC in our department have been analyzed and women younger th an 45 years old at the time of diagnosis and initial treatment were included. There were 40 women exposed to I131 (study group) and 11 women who were only treated with thyroidectomy (control group). Of the women exposed to I131, 40% went through early menopause, while no cases were reported among their controls. Furthermore, 29.2% of women exposed to I131 had decreased Antimüllerian Hormone (AMH), compared to the only 11% of unexposed women (not significant). Regarding the fertility impairment "perceived" by patients, in the group of women exposed to iodine, 17.9% described being unable to complete their genesic desire whereas, none was registered in the control group. We conclude that radioactive iodine can affect a woman's fertility and shorten her reproductive life, so this is an aspect that should be taken into consideration.

PMID:35260614 | DOI:10.1038/s41598-022-07592-8

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Concomitance or consequence? Stevens-Johnson syndrome in COVID-19: A case report

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Exp Ther Med. 2022 Apr;23(4):257. doi: 10.3892/etm.2022.11182. Epub 2022 Feb 2.

ABSTRACT

The novel coronavirus infection has been, and still is, a pressing medical problem with a catastrophic effect, not only from a medical point of view, but also from an economic and social one. The cutaneous manifestations of the disease have a diverse morphology and can signal the presence of the infection. The present article reports the case of a 77-year-old male patient admitted at The Sf. Parascheva Clinical Hospital of Infectious Diseases in Iasi (Romania) after testing positive for SARS CoV-2 infection. Initially, the patient presented a pruriginous generalized maculopapular-erythematous eruption with a tendency towards confluence, peri-oro-nasal meliceric crusts and desquamation of the skin on the third anterosuperior and posterior thorax, scalp and forehead, which was accompanied by low back pain, headache and orbital pain. The suspicion of Stevens-Johnson syndrome (SJS) was raised, and treatment was given according to the recommendation of the hospital dermatologist. This association raises multiple questions regarding whether SJS is a cutaneous manifestation of COVID-19 or if there was a concomitance between the viral infection and the immune reaction. The combination of SJS and COVID-19 can have a fatal outcome if not recognized and promptly treated. To our knowledge, this is the first case of SJS in a patient diagnosed with SARS CoV-2 infection in Romania.

PMID:35261629 | PMC:PMC8855504 | DOI:10.3892/etm.2022.11182

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Expression profile, clinical significance and biological functions of IGF2BP2 in esophageal squamous cell carcinoma

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Exp Ther Med. 2022 Apr;23(4):252. doi: 10.3892/etm.2022.11177. Epub 2022 Feb 1.

ABSTRACT

The ectopic expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been demonstrated to facilitate tumorigenesis and induce proliferation in a various types of cancer. However, the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) has yet been fully elucidated. In this regard, the current study assessed the expression patterns and clinical significance of IGF2BP2 in 94 Chinese patients diagnosed with ESCC. Immunohistochemistry and reverse transcription-quantitative PCR assays were employed to assess IGF2BP2 expression in ESCC tissues compared with adjacent healthy tissues. The results revealed that the protein expression of IGF2BP2 was substantially upregulated in ESCC tissues compared with adjacent ESCC tissues. More specifically, higher IGF2BP2 expression strongly associated with tumor node metastasis stage, ly mphatic infiltration and lymph node metastasis. Using two ESCC cell lines (TE-1 and TE-10), the inhibition of IGF2BP2 expression by small interfering RNA was proven to induce apoptosis and suppress proliferation, migration and cell cycle progression in vitro. Collectively, the present findings indicated that IGF2BP2 may serve a major role in the development of ESCC carcinogenesis. The present study may be helpful in the design of potential drug targets in the treatment of ESCC.

PMID:35261624 | PMC:PMC8855499 | DOI:10.3892/etm.2022.11177

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Cofilin-1 as a potential biomarker for Mycobacterium tuberculosis infection

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Exp Ther Med. 2022 Apr;23(4):253. doi: 10.3892/etm.2022.11178. Epub 2022 Feb 1.

ABSTRACT

Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tb), is one of the deadliest human infections worldwide. Our previous studies demonstrated cofilin-1 (CFL1) expression was significantly increased in exosomes from Mycobacterium avium (M. avium)-infected macrophages. The expression of CFL1 protein in M. tb infected hosts was investigated in the present study to predict whether CFL1 could have potential as a biomarker for M. tb infection. In the present study, the mRNA and protein expression levels of CFL1 in M. avium-infected macrophages and supernatants were analyzed via reverse transcription-quantitative PCR and western blotting. Furthermore, CFL1 expression in macrophages was knocked down in vivo, and then CFL1 expression levels in M. avium-infected macrophages and supernata nt were detected via western blotting and ELISA. In addition, CFL1 was detected in the peripheral blood mononuclear cells and plasma of patients with TB using western blotting and ELISA. The specificity and sensitivity of CFL1 as a biomarker and the association between TB infection and normal individuals were compared and analyzed using GraphPad Prism 5. CFL1 protein expression levels were significantly increased in M. avium-infected macrophages and supernatant. Meanwhile, CFL1 was upregulated in patients with TB. Bioinformatics statistics indicated the high specificity and sensitivity of CFL1 in patients with TB. Thus, these results suggest that CFL1 may act as a potential biomarker of TB infection.

PMID:35261625 | PMC :PMC8855514 | DOI:10.3892/etm.2022.11178

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PBX4 functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the PBX gene family

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Am J Cancer Res. 2022 Feb 15;12(2):585-600. eCollection 2022.

ABSTRACT

Pre-B-cell leukaemia (PBX) is a transcription factor family (PBX1, PBX2, PBX3 and PBX4) that regulates important cellular functions and has been identified to be involved in human cancers. This study aimed to explore the expression of PBX genes and their clinical significance in colorectal cancer (CRC). We analysed the differential expression of PBX genes in CRC vs. normal tissue, using the Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) and ONCOMINE platform (https://www.oncomine.org/). The UALCAN (http://ualcan.path.uab.edu/) interactive OMICS web-server was used to evaluate the epigenetic regulation of PBX genes via their promoter methylation status. We found that only PBX4 was upregulated whereas PBX1 and PBX3 were downregulated (644 tumour vs. 51 normal samples) (P<0.001). The methylation st atus of PBX4 promoter appeared to be decreased (P=1.4e-07) whereas the methylation status of PBX1 and PBX3 promoters was increased (P=3.8e-04 and P=3.2e-07, respectively) in cancer vs. normal samples. To determine the prognostic value of PBXs, we conducted a Kaplan-Meier survival analysis and multivariable COX regression. We observed that high PBX4 expression was associated with increased risk for a worse overall survival (OS) in the TCGA CRC patient cohort (n=639), (HR 1.46, 95% CI 1.14-1.88, P=0.003) adjusted for age, gender, tumour location and metastases. We conducted in vitro gene expression modulation experiments to investigate the impact of PBX4 overexpression in CRC cell (HCT116) growth. Additionally, we evaluated the RNA expression of epithelial-mesenchymal transition (EMT) and angiogenesis markers. In vitro studies showed that PBX4 overexpression increased CRC cell proliferation (P<0.001) and upregulated the expres sion of EMT markers VIM, CDH1, CDH2, ZEB1, SNAI1 (P<0.05) and angiomarker VEGFA (P<0.0001). Lastly, through the Cistrome data browser (http://dbtoolkit.cistrome.org/) we investigated putative transcriptional regulators and we performed gene set enrichment analysis in Enrichr server (https://maayanlab.cloud/Enrichr/) to identify related biological processes. Nineteen factors were identified to be putative regulators of PBX4 and gene set enrichment analysis showed that biological processes related to cell cycle and cell proliferation were enriched (GO:0051726: CDK8, JUN, JUND, and IRF1, P=0.001). In conclusion, our study identified PBX4 as a potential novel oncopromoter in CRC and its overexpression was found to be associated with increased risk for worse survival rate.

PMID:35261789 | PMC:PMC8899996

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Negative correlations of psychological distress with quality of life and immunotherapy efficacy in patients with advanced NSCLC

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Am J Cancer Res. 2022 Feb 15;12(2):805-815. eCollection 2022.

ABSTRACT

To evaluate the relationships between psychological distress and immunotherapy efficacy, adverse reactions and quality of life scores in patients with advanced non-small cell lung cancer (NSCLC). A total of 104 NSCLC patients who received 4-6 cycles of standard immunotherapy were enrolled and evaluated with the Distress Thermometer (DT) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The aim was to analyze the correlation between psychological distress and quality of life and to analyze whether psychological distress affects the efficacy of and adverse reactions to immunotherapy. The objective response rate (ORR) and disease control rate (DCR) of the psychological distress group were 6% and 50%, respectively, and those of the no psychological distress group were 18.5% and 83.3%, respectively. The differen ces were statistically significant (χ2=14.131, P<0.05). The progression-free survival (PFS) of advanced NSCLC patients who received comprehensive immunotherapy and had no psychological distress was significantly better than that of the psychological distress group (HR, 0.338; 95% CI, 0.192-0.592; P<0.05). The PFS of advanced NSCLC patients who received immunotherapy combined with chemotherapy in the no psychological distress group was significantly better than that in the psychological distress group (HR, 0.458; 95% CI, 0.296-0.709; P<0.05). Psychological distress in advanced NSCLC patients affects the efficacy of immunotherapy, and psychological distress is negatively correlated with quality of life during immunotherapy.

PMID:35261803 | PMC:PMC8899984

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The expression of cancer-testis antigen in ovarian cancer and the development of immunotherapy

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Am J Cancer Res. 2022 Feb 15;12(2):681-694. eCollection 2022.

ABSTRACT

Ovarian cancer is a relatively common tumor in women with the highest mortality among female reproductive system tumors. The lack of apparent early symptoms and effective screening strategies often leads to ovarian cancer being diagnosed at an advanced stage. Immunotherapy relying on tumor-associated antigens might improve the treatment of ovarian cancer. Cancer-testis antigens (CTAs) are ideal tumor-associated antigens, and MAGE-A, NY-ESO-1, CT45, and Sp17 are classic CTAs highly expressed in ovarian cancer. Here, we review the research on CTAs in ovarian cancer, including prognostic value and advances in immunotherapy, all of which are essential for developing a theoretical basis for targeted therapy strategies.

PMID:35261795 | PMC:PMC8899981

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Multimodality imaging in the assessment of bone marrow-derived mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy

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Am J Cancer Res. 2022 Feb 15;12(2):574-584. eCollection 2022.

ABSTRACT

Due to their broad-spectrum effects and high antitumor efficacies, anthracycline-based chemotherapies are commonly prescribed in various solid and hematological malignancies. Doxorubicin (DOX) is one of the most highly used anthracyclines but has been shown to cause lethal cardiomyopathy in clinical practice. Studies have demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to rescue DOX-induced cardiomyopathy (DIC). However, novel molecular imaging techniques are required to explore the biological behaviors, safety, eventual viability, and environmental interactions of transplanted stem cells during therapy. To investigate the biological behaviors of transplanted BMSCs, we applied bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) techniques to trace firefly luciferase (Fluc) and ultrasmall superparamagnetic iron oxi de (USPIO) double-labeled mouse BMSCs after injection into the heart apex in a chronic DIC mouse model. Then, we determined the optimal BMSC number for transplantation into the heart and optimized MRI parameters to evaluate transplanted BMSCs in vitro and in vivo. Our results showed that the BLI trace signal could last 7 days in the DIC mouse model, whereas the MRI signal lasted up to 3 days. However, MRI provided more detailed pathophysiological information on DIC than BLI, such as inflammation and fibrosis signs. The optimal in vivo cell number for BLI and MRI was determined to be 1×106. In conclusion, BLI combined with multimodality MRI could be used to monitor the biological behavior of BMSCs transplanted into a chronic DIC mouse model in a visual and dynamic manner.

PMID:35261788 | PMC:PMC8899982

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A novel HDAC11 inhibitor potentiates the tumoricidal effects of cordycepin against malignant peripheral nerve sheath tumor through the Hippo signaling pathway

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Am J Cancer Res. 2022 Feb 15;12(2):873-892. eCollection 2022.

ABSTRACT

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder. Clinically, the hallmarks of NF1 include skin pigmentation and cutaneous neurofibroma. Some NF1 patients develop plexiform neurofibroma (PN) since early childhood. Pathologically, PN contains abundant Schwann cells, blood vessels and connective tissues, which may transform into a malignant peripheral nerve sheath tumor (MPNST). MPNST is a highly invasive sarcoma without any effective therapy. Recently, both in vitro and in vivo studies showed that cordycepin can inhibit the growth of MPNST cells. Cordycepin causes cell cycle arrest at G2/M phase and downregulates the protein levels of α-tubulin, p53 and Sp1. Herein, the present study revealed that the HDAC11 inhibitor, FT895, can synergistically enhance the tumoricidal effect of cordycepin against MPNST cells in vitro< /i>. Treatment with the combination of cordycepin and FT895 reduced the size of MPNST in the xenograft mouse model. The combined treatment decreased the protein levels of α-tubulin and KIF18A, which may disrupt the microtubule organization leading to the mis-segregation of chromosomes and aneuploidy. Moreover, the expression levels of TEAD1 and its co-activator TAZ, the candidate proteins in hippo signaling pathway, were suppressed after combined treatment. Sequence analysis found a few binding sites for the transcription factor, TEAD1 in the promoter regions of TUBA1B, KIF18A, TEAD1, TAZ, YAP, TP53 and SP1 genes. ChIP-qPCR assay showed that the combined treatment decreases the binding of TEAD1 to the promoters of TUBA1B, KIF18A, TEAD1, TAZ and YAP genes in STS26T cells. The reduced binding to TP53 and SP1 promoters was also found in S462TY cells, which was further confirmed by immunoblotting. The down-regulation of these important transcri ptional factors may contribute to the vulnerability of MPNST. In summary, HDAC11 inhibitor, FT895 can potentiate the tumoricidal effect of cordycepin to suppress the MPNST cell growth, which was probably mediated by the dysfunction of hippo-signaling pathway.

PMID:35261809 | PMC:PMC8899988

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Trastuzumab in combination with PEGylated interferon-α1b exerts synergistic antitumor activity through enhanced inhibition of HER2 downstream signaling and antibody-dependent cellular cytotoxicity

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Am J Cancer Res. 2022 Feb 15;12(2):549-561. eCollection 2022.

ABSTRACT

The anti-HER2 monoclonal antibody trastuzumab is the mainstay of treatment for HER2-positive breast and gastric cancer, and its combination with multiple chemotherapeutic agents has represented an effective and rational strategy in the clinic. In this study, we report that trastuzumab in combination with PEGylated interferon-α1b (IFN-α1b), a polyethylene glycol (PEG)-conjugated form of a subtype of interferon alpha (IFN-α), synergistically inhibited the proliferation of HER2-positive cells, including BT-474 and SK-BR-3 breast cancer cells and NCI-N87 gastric cancer cells, and also induced their apoptosis, but had no effect on HER2-negative MDA-MB-231 breast cancer cells. Trastuzumab inhibited phosphorylation of HER2, AKT and ERK, an effect that was enhanced by PEGylated IFN-α1b, likely owing to PEGylated IFN-α1b-mediated downregulation of HER2 through the lysos omal degradation pathway. Moreover, PEGylated IFN-α1b significantly enhanced trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) in HER2-positive cells. Importantly, trastuzumab combined with PEGylated IFN-α1b exhibited significant synergistic antitumor activity in HER2-positive BT-474 xenografts, an effect that was associated with enhanced inhibition of HER2 expression and AKT and ERK phosphorylation. Strikingly, depletion of natural killer cells with anti-Asialo GM1 antibody abrogated the synergistic antitumor activity, indicating that augmented ADCC is essential for this synergy. Taken together, our findings indicate that both enhanced inhibition of HER2 downstream signaling and augmented ADCC contribute to the synergistic antitumor activity of trastuzumab with PEGylated IFN-α1b, and imply that combining trastuzumab with PEGylated IFN-α1b could be a promising strategy for HER2-positive cancers.

PMID:35261786 | PMC:PMC8899978

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