Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Wednesday, May 5, 2021

Primary external auditory canal cholesteatoma

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Eur Arch Otorhinolaryngol. 2021 May 4. doi: 10.1007/s00405-021-06851-0. Online ahead of print.

ABSTRACT

PURPOSE: Limited literature exists on primary external auditory canal (EAC) cholesteatoma (EACC). Here, we focus on the clinical features of this rare disease, especially the invasive patterns of lesion progression, through a large population study and present simple and practical staging.

METHODS: In all, 276 patients (male 99; female 177; mean age 41.3 ± 21 years; ears 301) with primary EACC were retrospectively analyzed. Stage I indicated EACC without bony lesions, stage II indicated invasion confined within EAC, stage III indicated invasion beyond the EAC involving mastoid air cells or tympanic cavity, but within the temporal bone, and stage IV indicated invasion beyond the temporal bone.

RESULTS: In all, 41, 219, 40, and 1 ear with Stage I, II, III, and IV lesions were found, respectively. Common clinical symptoms w ere hearing loss (237 ears, 78.7%), otalgia (221 ears, 73.4%), and otorrhea (85 ears, 28.2%). The mean air conduction and air-bone gaps were 45.4 ± 17.9 dB HL and 24.6 ± 15 dB HL, respectively. EACCs were found to invade in all directions of the EAC, with the inferior wall (224 ears, 74.4%) > posterior wall (207 ears, 68.8%) > anterior wall (186 ears, 61.8%) > superior wall (86 ears, 28.6%) invasion; multiwall invasions (207 ears) were common; however, inward invasions into the tympanic cavity were rare.

CONCLUSION: Primary EACCs occurred mostly in women and often unilaterally invaded multiple bony walls in the lower half of the EAC. The present staging reflects the patterns and severity of lesion progression and may be beneficial in treatment planning.

PMID:33948680 | DOI:10.1007/s00405-021-06851-0

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q-Powders: a quick test for screening retronasal olfactory disorders with tasteless powders

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Eur Arch Otorhinolaryngol. 2021 May 4. doi: 10.1007/s00405-021-06849-8. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the clinical utility of q-Powders-a retronasal identification screening test.

METHODS: A total of 156 subjects (92 females, mean age: 54.5 years ± 17.3 years) completed a 3-item q-Powders retronasal identification test and a 16-items Sniffin' Sticks orthonasal identification test. We analyzed whether the q-Powders test could differentiate between subjects with normosmia and subjects with an olfactory disorder.

RESULTS: Our data indicated that subjects with an olfactory disorder scored lower in the q-Powders test than subjects with normosmia. The analyses revealed q-Powders test sensitivity of 84% and a test specificity of 64.9% with a score of 2 points taken as a cutoff for olfactory disorders.

CONCLUSION: The 3-item q-Powders retronasal test may be used for screening purposes in clinical re search.

LEVEL OF EVIDENCE: 4.

PMID:33948681 | DOI:10.1007/s00405-021-06849-8

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Weathering the Storm: Thyroid Storm Precipitated by Radioiodine Contrast in Metastatic Thyroid Carcinoma

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Cureus. 2021 Mar 31;13(3):e14219. doi: 10.7759/cureus.14219.

ABSTRACT

Thyroid storm is an extremely rare yet life-threatening medical emergency. It results from the decompensation of undiagnosed or undertreated hyperthyroidism in the presence of an acute stressor such as trauma to the thyroid, infections, acute iodine load, withdrawal from the antithyroid medication, or surgical procedures (including thyroid surgery). Clinical features of thyroid storm include hyperthermia, tachyca rdia, respiratory distress, gastrointestinal and hepatic symptoms, and central nervous system dysfunction. It is primarily a clinical diagnosis, further aided by abnormal thyroid function tests. Thyroid storm is associated with significant mortality and morbidity - the latter mostly related to complications from thyrotoxicosis or hyperthyroidism. Treatment with iodine (or iodide-ionized active form of iodine) supplements or with radioactive iodine, also known as radioiodine, such as in the treatment of thyroid cancer, is a common and mostly safe practice; however, iodine contrast in tomography imaging may precipitate a thyroid storm in sporadic cases. Here, we report a remarkable case of a 62-year-old African American female with a history of total thyroidectomy secondary to follicular thyroid cancer three years before the current presentation; she developed left lung pneumonia complicated by thyroid storm status post a computed tomography angiogram of the abdomen. She exhibited sig ns and symptoms of thyrotoxicosis a few days after receiving the iodinated contrast. The recommended daily iodide intake for adults with hyperthyroidism is about 150 mcg per day, while a computed tomography scan exposes patients to 14 to 35 million mcg of iodinated contrast at once, which could have triggered a storm. In this case, the patient was diagnosed with thyroid storm, which was presumed to be a consequence of the Jod-Basedow phenomenon secondary to metastatic thyroid carcinoma lesions discovered later. This clinical diagnosis was reinforced by laboratory results showing elevated serum free T4 and undetectable thyroid-stimulating hormone. She was treated with supportive measures, steroids, beta-blockers, and antithyroid medications with a positive outcome. This case demonstrated that, in the setting of recurrent metastatic thyroid cancer, clinicians should approach the use of intravenous iodine medium contrast in imaging with some level of caution when dealing with patients at risk of thyrotoxicosis or with underlying hyperthyroidism state at the brink of a storm.

PMID:33948409 | PMC:PMC8086751 | DOI:10.7759/cureus.14219

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MEX3A suppresses proliferation and EMT via inhibiting Akt signaling pathway in cervical cancer

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Am J Cancer Res. 2021 Apr 15;11(4):1446-1462. eCollection 2021.

ABSTRACT

MEX3A, one member of the human MEX3 gene family, exerts different effects on a variety of human cancer cells. However, the biological functions and regulatory mechanism have not been explored in cervical cancer. In our study, we used multiple approaches to determine the functions and underlying molecular mechanism of MEX3A in cervical tumorigenesis, including CCK-8 assay, BrdU assay, FACS for cell cycle and apoptosis, wound healing assay, Transwell migration and invasion assays, immunohistochemistry (IHC) assay, Transfection, real-time RT-PCR and Western blotting analysis. IHC results showed that the expression levels of MEX3A were decreased in cervical cancer patients with advanced clinical stages and lymph node involvement. Moreover, upregulation of MEX3A attenuated cell proliferation, migration and invasion and induced cell cycle arrest at G0/G1 phase in human cervical cancer cells, whereas knockdown of MEX3A exhibited the opposite effects. Mechanistically, MEX3A exerted its tumor suppressive functions via inactivation of Akt signaling pathway and inhibiting epithelial to mesenchymal transition (EMT). Importantly, Akt activation by its activator SC79 reversed the biological functions of MEX3A overexpression. Furthermore, MEX3A inhibited tumor growth in xenograft models. Overall, our investigation suggested that MEX3A participated in antitumor activity in cervical cancer by inhibition of the Akt signaling pathway and EMT. Hence, targeting MEX3A might have a therapeutic potential to treat cervical cancer.

PMID:33948367 | PMC:PMC8085868

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CRISPR screen in cancer: status quo and future perspectives

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Am J Cancer Res. 2021 Apr 15;11(4):1031-1050. eCollection 2021.

ABSTRACT

Clustered regularly interspaced short palindromic repeats (CRISPR) system offers a powerful platform for genome manipulation, including protein-coding genes, noncoding RNAs and regulatory elements. The development of CRISPR screen enables high-throughput interrogation of gene functions in diverse tumor biologies, such as tumor growth, metastasis, synthetic lethal interactions, therapeutic resistance and immunotherapy response, which are mostly performed in vitro or in transplant models. Recently, direct in vivo CRISPR screens have been developed to identify drivers of tumorigenesis in native microenvironment. Key parameters of CRISPR screen are constantly being optimized to achieve higher targeting efficiency and lower off-target effect. Here, we review the recent advances of CRISPR screen in cancer studies both in vitro and in vivo, wi th a particular focus on identifying cancer immunotherapy targets, and propose optimizing strategies and future perspectives for CRISPR screen.

PMID:33948344 | PMC:PMC8085856

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A population-based study: how to identify high-risk T1 gastric cancer patients?

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Am J Cancer Res. 2021 Apr 15;11(4):1463-1479. eCollection 2021.

ABSTRACT

In T1 gastric cancer (GC), lymph nodes metastasis (LNM) is considered as a significant prognostic predictor and closely associated with following therapeutic approaches as well as distant metastasis (DM). This study aimed to not only seek risk factors of LNM and DM but also unpack the prognosis in T1 GC patients. We performed a retrospective study enrolling 5547 patients in T1 GC from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression models were produced to recognize independent risk factors of LNM and DM. Cox regression analyses were performed to identify important prognostic factors of overall survival (OS). Cancer-specific cumulative incidence was plotted by cumulative incidence function. Three nomograms of LNM, DM and OS were established and validated by receiver operating characteristic (ROC) and calibration curves to evaluate discrimination and accuracy. Decision curve analysis (DCA), clinical impact curves (CIC) and subgroups based on risk scores were constructed to measure nomograms clinical utility. The area under the curve (AUC) of LNM nomogram and DM nomogram were 0.735 and 0.896, respectively. OS nomogram was constructed and the corresponding C-index was 0.797. In conclusion, our user-friendly nomograms, which aimed to predict LNM, DM and OS in T1 gastric cancer patients, have shown high efficiency of discrimination and accuracy. These useful and visual tools may have advantageous clinical utility to identify high-risk T1 gastric patients and help clinicians to draw up an individual therapeutic strategy.

PMID:33948368 | PMC:PMC8085846

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Tumor-treating fields (TTFields)-based cocktail therapy: a novel blueprint for glioblastoma treatment

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Am J Cancer Res. 2021 Apr 15;11(4):1069-1086. eCollection 2021.

ABSTRACT

Glioblastoma is one of the most common malignant tumors in the central nervous system. Due to the high plasticity, heterogeneity and complexity of the tumor microenvironment, these tumors are resistant to almost all therapeutic strategies when they reach an advanced stage. Along with being a unique and effective way to kill cancer cells, tumor-treating fields (TTFields) has emerged as a breakthrough among glioblastoma therapies since the advent of temozolomide (TMZ), and the combination of these treatments has gradually been promoted and applied in the clinic. The combination of TTFields with other therapies is particularly suitable for this type of "cold" tumors and has attracted a large amount of attention from clinicians and researchers in the era of cancer cocktail therapy. Here, we introduced the current treatment regimen for glioblastoma, highlighting the un ique advantages of TTFields in the treatment of glioblastoma. Then, we summarized current glioblastoma clinical trials that combine TTFields and other therapies. In addition, the main and potential mechanisms of TTFields were introduced to further understand the rationale for each combination therapy. Finally, we focused on the most advanced technologies applied in glioblastoma research and treatment and the prospect of their combination with TTFields. This review provides a unique overview of glioblastoma treatment.

PMID:33948346 | PMC:PMC8085847

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The PVT1/miR-612/CENP-H/CDK1 axis promotes malignant progression of advanced endometrial cancer

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Am J Cancer Res. 2021 Apr 15;11(4):1480-1502. eCollection 2021.

ABSTRACT

Our previous study introduced the oncogenic role of the long non-coding RNA plasmacytoma variant translocation 1 (PVT1) in endometrial cancer (EC). In this study, we aimed to construct a PVT1-centered competing endogenous RNA (ceRNA) network to outline a regulatory axis that might promote the malignant progression of advanced EC. Raw Uterine Corpus Endometrial Carcinoma (UCEC) datasets were collected from The Cancer Genome Atlas (TCGA) database and used for construction of the PVT1-centered ceRNA network. The ceRNA binding sites were established using dual-luciferase assays. FISH assays displayed the co-location of PVT1 and miR-612 in EC cells. Immunohistochemistry, in situ hybridization, qRT-PCR, and western blots were used to assess the expression of miR-612 and CENP-H in EC tissues, and their functions on biological behaviours were examined by a series of in vitro and in vivo assays. Molecule interactions were illustrated by co-transfection assays. The bioinformatics analysis showed that PVT1/miR-612/CENP-H/CDK1 axis played a vital role in the malignant progression of advanced EC. MiR-612 was downregulated in EC tissues and acted as a tumour suppressor to inhibit cell proliferation, migration, invasion, and promote cell apoptosis. CENP-H was found overexpressed in EC tissues, and the expression level was correlated to diagnosis and prognosis of EC. Hyperactivated CENP-H promoted cell proliferation, migration, invasion, and inhibited cell apoptosis. Overexpressed CENP-H prevented the anti-tumour effects observed with upregulated miR-612; knockdown of miR-612 also suppressed the anti-tumour effects of downregulated PVT1. Knockdown of PVT1 together with upregulated miR-612 exerted the strongest anti-tumour effects in nude mice. These effects were mediated by CDK1 through modulation of the Akt/mTOR signaling pathway. In conclusi on, the PVT1/miR-612/CENP-H/CDK1 axis promoted the malignant progression of advanced EC and could serve as a promising target for potential treatments.

PMID:33948369 | PMC:PMC8085881

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B-cell acute lymphoblastic leukemia-related microRNAs: uncovering their diverse and special roles

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Am J Cancer Res. 2021 Apr 15;11(4):1104-1120. eCollection 2021.

ABSTRACT

B-cell acute lymphoblastic leukemia (B-ALL) is a common type of hematologic malignancy characterized by the uncontrolled growth of immature B lymphocytes. Genomics, transcriptomics, and proteomics at different levels contribute to early diagnosis and can thereby provide better treatment for cancer. MicroRNAs (miRNAs) are conducive to the diagnosis and treatment of patients with B-ALL. Moreover, evidence suggests that runaway miRNAs and exosomes containing miRNA may be involved in the occurrence of B-ALL, which can then be used as potential biomarkers. This review summarizes the role of miRNAs in the pathogenesis, diagnosis, prognosis, and treatment of B-ALL.

PMID:33948348 | PMC:PMC8085864

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A therapeutic approach with combination of interferon-gamma and autophagy inhibitor for oral squamous cell carcinoma

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Am J Cancer Res. 2021 Apr 15;11(4):1503-1521. eCollection 2021.

ABSTRACT

Former clinical trials and experimental research have indicated that Interferon-gamma therapy does not achieve an ideal effect in solid tumors. Autophagy has been associated with tumor chemoresistance. The aim of this study was to explore the efficacy of Interferon-gamma and autophagy inhibitor in the combination treatment of oral squamous cell carcinoma. Interferon-gamma-induced apoptosis was evaluated by the expression of relative proteins (cleaved-PARP and caspase-3) and flow cytometry. Interferon-gamma induced autophagy was assessed by the expression of Beclin1, LC3B, and P62. The synergistic effect of interferon-gamma and autophagy inhibitor (chloroquine) was evaluated in vitro and in vivo. Interferon-gamma induced anti-proliferation, apoptosis, and autophagy in oral squamous cell carcinoma cells. Autophagy-related protein 5 was a key feature in Interferon-gamma-induced autophagy flux. Interferon-gamma and chloroquine had obvious synergistic effects on cellular growth inhibition and apoptosis promotion in oral squamous cell carcinoma cells and xenograft models. Our findings suggest that Interferon-gamma-induced autophagy plays a cellular protective role, and blocking autophagy flux can promote Interferon-gamma mediated oral squamous cell carcinoma cell apoptosis. The combination of Interferon-gamma and autophagy inhibitors represents a novel strategy for oral squamous cell carcinoma therapy.

PMID:33948370 | PMC:PMC8085849

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Cardiotoxicity of chemotherapy and targeted agents

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Am J Cancer Res. 2021 Apr 15;11(4):1132-1147. eCollection 2021.

ABSTRACT

The evolution of cancer treatment and development of new classes of anticancer therapies have continued to revolutionize the field of oncology. New therapies including targeted agents, immunotherapies, and adoptive cell transfer have allowed for exciting survival benefit progress for patients. However, the novel nature of these therapies as well as the longer survival periods of patients receiving them has highlighted the various side effects of anticancer therapies. Cardiotoxicity has emerged as a major side effect of anticancer treatment and can present both acutely during treatment and chronically even years after treatment has been completed. This work compiles the cardiotoxic side effects of various chemotherapeutic and targeted anticancer therapies and their management.

PMID:33948350 | PMC:PMC8085845

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