Surgical Risk Prediction for Nasolacrimal Duct Obstruction in Radioactive Iodine-Treated Thyroid Cancer: A Nationwide Cohort Study

xlomafota13 shared this article with you from Inoreader Surgical Risk Prediction for Nasolacrimal Duct Obstruction in Radioactive Iodine-Treated Thyroid Cancer: A Nationwide Cohort Study Via liebertpub1 Thyroid, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cochlear implant in vestibular schwannomas: long-term outcomes and critical analysis of indications

xlomafota13 shared this article with you from Inoreader Cochlear implant in vestibular schwannomas: long-term outcomes and critical analysis of indications Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2022 Jan 12. doi: 10.1007/s00405-021-07243-0. Online ahead of print. ABSTRACT PURPOSE: To describe our institutional experience in cochlear implantation after vestibular schwannoma (VS) resection, and compare the audiological outcomes between sporadic and neurofibromatosis type 2 (NF2) VS sub-cohorts of patients, and in relation to preoperative contralateral hearing. METHODS: Seventeen patients (8 sporadic and 9 NF2-associated VSs) who had undergone VS resection and cochlear implant (CI) were analyzed retrospectively. Audiological outcomes at 24 months were correlated with preoperative clinical variables. The results according to VS type (sporadic vs. NF2-associated) and contralateral hearing (impaired vs. normal) were compared. RESULTS: Fourteen CIs were actively used by the patients (77.8%). Twenty-four months after CI activation, the median postoperative PTA (pure tone average) was 45.6 dB nHL and a measurable WRS (Word Recognition Score) was achieved by 44.4% of patients (median WRS = 40%). The median postoperative PTA in the implanted ear resulted better in the group with an impaired contralateral hearing (36.3 dB nHL vs. 78.8 dB nHL, p = 0.019). Good preoperative contralateral hearing status (A-B classes of AAO-HNS) was a negative prognostic factor for CI performance on open-set discrimination (OR = 28.0, 95% CI 2.07-379.25, p = 0.012). CONCLUSIONS: CI is a viable rehabilitative option for patients with sporadic or NF2-associated VS. A good contralateral hearing adversely affects CI outcome and should be taken into consideration for patients' selection and rehabilitation programs. PMID:35018505 | DOI:10.1007/s00405-021-07243-0 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cerebrospinal fluid external leak after penetrating trauma in a neurologic intact infant patient: a case report

xlomafota13 shared this article with you from Inoreader Cerebrospinal fluid external leak after penetrating trauma in a neurologic intact infant patient: a case report Via leak of cerebrospinal fluid Childs Nerv Syst. 2022 Jan 12. doi: 10.1007/s00381-021-05440-0. Online ahead of print. ABSTRACT Cranial cerebrospinal fluid (CSF) leak is an extremely rare complication of blunt head trauma causing skull fractures, especially fractures involving the skull base. We present the case of a 10-month-old male who received glass fragments on the midline and posterior tier of his anterior fontanelle producing a cranial cerebrospinal fluid leak without any skull fracture or symptoms. Neurologic exam was completely normal and a superficial stitch wound repair was performed. He was observed for 24 h, had no antibiotic, and left with a 1-week outpatient neurosurgical follow-up. The patient had no negative outcome. Cerebrospinal fluid leak should be included in the differential diagnosis of a head trauma in a patient with open fontanelles. No similar case was found in literature. PMID:35019999 | DOI:10.1007/s00381-021-05440-0 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

PI3-kinase inhibition as a strategy to suppress the leukemic stem cell niche in Ph+ chronic myeloid leukemia

xlomafota13 shared this article with you from Inoreader PI3-kinase inhibition as a strategy to suppress the leukemic stem cell niche in Ph+ chronic myeloid leukemia Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6042-6059. eCollection 2021. ABSTRACT Recent data suggest that the disease-associated microenvironment, known as the leukemic stem cell (LSC) niche, is substantially involved in drug resistance of LSC in BCR-ABL1+ chronic myeloid leukemia (CML). Attacking the LSC niche in CML may thus be an effective approach to overcome drug resistance. We have recently shown that osteoblasts are a major site of niche-mediated LSC resistance against second- and third-generation tyrosine kinase inhibitors (TKI) in CML. In the present study, we screened for drugs that are capable of suppressing the growth and viability of osteoblasts and/or other niche cells and can thereby overcome TKI resistance of CML LSC. Proliferation was analyzed by determining 3H-thymidine uptake in niche-related cells, and apoptosis was measured by Annexin-V/DAPI-staining and flow cytometry. We found that the dual PI3 kin ase (PI3K) and mTOR inhibitor BEZ235 and the selective pan-PI3K inhibitor copanlisib suppress proliferation of primary osteoblasts (BEZ235 IC50: 0.05 μM; copanlisib IC50: 0.05 μM), the osteoblast cell line CAL-72 (BEZ235 IC50: 0.5 μM; copanlisib IC50: 1 μM), primary umbilical vein-derived endothelial cells (BEZ235 IC50: 0.5 μM; copanlisib IC50: 0.5 μM), and the vascular endothelial cell line HMEC-1 (BEZ235 IC50: 1 μM; copanlisib IC50: 1 μM), whereas no comparable effects were seen with the mTOR inhibitor rapamycin. Furthermore, we show that BEZ235 and copanlisib cooperate with nilotinib and ponatinib in suppressing proliferation and survival of osteoblasts and endothelial cells. Finally, BEZ235 and copanlisib were found to overcome osteoblast-mediated resistance against nilotinib and ponatinib in K562 cells, KU812 cells and primary CD34+/CD38- CML LSC. Together, targ eting osteoblastic niche cells through PI3K inhibition may be a new effective approach to overcome niche-induced TKI resistance in CML. Whether this approach can be translated into clinical application and can counteract drug resistance of LSC in patients with CML remains to be determined in clinical trials. PMID:35018241 | PMC:PMC8727792 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers

xlomafota13 shared this article with you from Inoreader The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):5833-5855. eCollection 2021. ABSTRACT Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is widely known as a tumor suppressor gene. It is located on chromosome 10q23 with 200 kb, and has dual activity of both protein and lipid phosphatase. In addition, as a targeted gene in multiple pathways, PTEN has a variety of physiological activities, such as those regulating the cell cycle, inducing cell apoptosis, and inhibiting cell invasion, etc. The PTEN gene have been identified in many kinds of cancers due to its mutations, deletions and inactivation, such as lung cancer, liver cancer, and breast cancer, and they are closely connected with the genesis and progression of cancers. To a large extent, the tumor suppressive function of PTEN is realized through its inhibition of the PI3K/AKT signaling pathway which controls cells apoptosis and development. In addition, PTEN loss has been associate d with the prognosis of many cancers, such as lung cancer, liver cancer, and breast cancer. PTEN gene is related to many cancers and their pathological development. On the basis of a large number of related studies, this study describes in detail the structure, regulation, function and classical signal pathways of PTEN, as well as the relationship between various tumors related to PTEN. In addition, some drug studies targeting PTEN/PI3K/AKT/mTOR are also introduced in order to provide some directions for experimental research and clinical treatment of tumors. PMID:35018228 | PMC:PMC8727805 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diacerein, an inhibitor of IL-1β downstream mediated apoptosis, improves radioimmunotherapy in a mouse model of Burkitt's lymphoma

xlomafota13 shared this article with you from Inoreader Diacerein, an inhibitor of IL-1β downstream mediated apoptosis, improves radioimmunotherapy in a mouse model of Burkitt's lymphoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6147-6159. eCollection 2021. ABSTRACT Lymphoma has the characteristics of a solid tumor. Penetration of monoclonal antibodies is limited in solid tumors during radioimmunotherapy (RIT). Here, we first investigated the use of diacerein (DIA) as a combination drug to improve the penetration and therapeutic efficacy of 131I-rituximab (RTX) using the Burkitt's lymphoma mouse model. We selected DIA through computational drug repurposing and focused on rheumatoid arthritis (RA) drug interaction genes to minimize side effects. Then, the cytotoxicity of DIA was assessed in vitro using three different lymphoma cell lines. DIA-induced apoptosis was confirmed by Western blotting. After confirming apoptosis, we confirmed the enhanced uptake of 131I-RTX in Burkitt's lymphoma mouse model using SPECT/CT. Autoradiography of 131I-RTX confirmed the therapeutic effect of DIA. Finally, t he tumor size and survival rate were assessed to measure the enhanced therapeutic efficacy when DIA was used. In addition, we assessed the dose-dependency of DIA in terms of the accumulation of 131I-RTX in tumor tissue, the tumor size, and the survival rate. The in vitro cytotoxicity was 10.9%. We showed that DIA induced apoptosis which was related to downstream IL-1β signaling by Western blotting. We found increased Annexin V positive apoptosis after DIA administration. Immuno SPECT/CT images demonstrated a higher uptake of 131I-RTX in tumors in the DIA-administered group than that in the PBS-alone group. However, there were no statistical differences of dose-dependency between 20 mg/kg and 40 mg/kg of DIA. Tumor growth was significantly inhibited in the group treated with the combination of DIA plus 131I-RTX at 7 days after injection. Our suggested combination of DIA and 131I-RTX strategies could enhance the efficacy of 131I -RTX treatment. PMID:35018248 | PMC:PMC8727812 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Calcitriol induces estrogen receptor alpha expression through direct transcriptional regulation and epigenetic modifications in estrogen receptor-negative breast cancer cells

xlomafota13 shared this article with you from Inoreader Calcitriol induces estrogen receptor alpha expression through direct transcriptional regulation and epigenetic modifications in estrogen receptor-negative breast cancer cells Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):5951-5964. eCollection 2021. ABSTRACT Patients with estrogen receptor (ER) α-negative breast tumors have a poor prognosis and are not suitable for hormone therapy. Previously, we demonstrated that calcitriol, the active metabolite of vitamin D, induces ERα expression and re-establishes the response to antiestrogens in ER-negative breast cancer cells. However, the mechanisms involved in this process have not been elucidated. Therefore, the present study was undertaken to investigate the mechanisms implicated in the calcitriol-induced ERα expression in ER-negative breast cancer cells. Using EMSA and ChIP assays, we found that the calcitriol/vitamin D receptor (VDR)/retinoic X receptor (RXR) complex binds to putative vitamin D response elements (VDREs) in the ERα gene promoter region. In addition, we established by a fluorometric assay that calcitriol decreased DNA-methyltransferase and histone deac etylase activities. Flow cytometry and qPCR analyses showed that co-treatment of calcitriol with inhibitors of the histone deacetylase and DNA methyltransferase, and genistein significantly increased ERα expression, compared to that observed with the compounds alone. In conclusion, the calcitriol-dependent ERα induction in ER-negative breast cancer cells results from binding of the VDR-RXR complex to VDREs in the ERα gene promoter region, including the downregulation of enzymes with chromatin-remodeling activities. These results may bring forth novel mechanistic knowledge into the actions of calcitriol in ERα-negative breast cancer. PMID:35018235 | PMC:PMC8727803 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Truncating CDKN1A mutations: an insight into the biology of urinary tract carcinomas?

xlomafota13 shared this article with you from Inoreader Truncating <em>CDKN1A</em> mutations: an insight into the biology of urinary tract carcinomas? Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6214-6217. eCollection 2021. ABSTRACT A recent in silico study by Arnoff and El-Deiry found that urothelial carcinomas of the bladder and upper tract as well as chromophobe renal cell carcinoma are more likely than other malignancies to harbor alterations in the CDKN1A gene, encoding for the cyclin-dependent kinase inhibitor p21Waf1, a major target of p53 regulatory pathways. Most of these mutations were truncating and thus presumably resulting in loss of p21Waf1 function. Herein, we discuss the prognostic and therapeutic implications of these findings. PMID:35018253 | PMC:PMC8727807 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.