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.

Clinicopathological features and outcome of thyroglobulin elevation and negative iodine scintigraphy (TENIS) patients with negative neck ultrasound: Experience from a thyroid carcinoma clinic in India

xlomafota13 shared this article with you from Inoreader Clinicopathological features and outcome of thyroglobulin elevation and negative iodine scintigraphy (TENIS) patients with negative neck ultrasound: Experience from a thyroid carcinoma clinic in India Via radioactive iodine World J Nucl Med. 2021 Nov 1;20(4):361-368. doi: 10.4103/wjnm.wjnm_143_20. eCollection 2021 Oct-Dec. ABSTRACT Management of differentiated thyroid carcinoma (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy (TENIS) and negative neck ultrasound scan causes considerable diagnostic and therapeutic dilemma, especially in resource-poor settings. The aim of this study was to evaluate clinicopathological features and outcome of TENIS patients with negative n eck US attending a thyroid cancer clinic in India. From a DTC database of 722 containing 193 TENIS patients, subjects with negative neck US and negative Tg antibody (TgAb) were selected retrospectively and analyzed using appropriate statistical methods. The study group included 64 patients (male - 17, female - 47, mean age - 44.7 ± 12.8 years) with 54 papillary and 10 follicular thyroid carcinomas, American Thyroid Association (ATA) recurrence risk categorization (2009) - low - 16, intermediate - 28, and high - 2 0. Most of the patients became TENIS within 1 year of diagnosis with median Tg level of 6.5 ng/mL (1.2-996 ng/mL) and mean follow-up of 7.8 years. On follow-up, Tg dropped spontaneously in 27 patients, more among the low and intermediate-risk categories. For those with high or increasing Tg level, further imaging (fluorodeoxyglucose positron emission tomography/computed tomography) was done and 14 out of 18 were positive. Treatment included empiric radioactive iodine thera py-16, external beam radiation therapy (EBRT)-7, and lymph node dissection (LND)-10. A favorable outcome was seen in 36 patients and unfavorable in 28. Distant metastases were associated with unfavorable outcome and poor survival. Progression-free survival was significantly better in the Tg group of <10 at the time of TENIS (111 months) compared to the Tg group >10 (72 months). Tg level dropped spontaneously in nearly half the patients, especially if levels were <10 and more so among the low-risk category. Distant metastasis was predictive of unfavorable outcomes. Along with Tg level, the ATA risk category might help to predict clinical course and reduce unnecessary expensive imaging in resource-poor settings. PMID:35018 151 | PMC:PMC8686749 | DOI:10.4103/wjnm.wjnm_143_20 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.

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.

Assessment of age, period, and cohort effects of lung cancer incidence in Hong Kong and projection up to 2030 based on changing demographics

xlomafota13 shared this article with you from Inoreader Assessment of age, period, and cohort effects of lung cancer incidence in Hong Kong and projection up to 2030 based on changing demographics Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):5902-5916. eCollection 2021. ABSTRACT The burden of lung cancer in Hong Kong continues to rise. We analyzed trends in lung cancer incidence and associations with age, period, and cohort from 1985 to 2019, made projections up to 2030 and examined the drivers of lung cancer incidence. We used age-period-cohort modeling to estimate age, period, and cohort effects on lung cancer incidence rates in Hong Kong between 1985 and 2019. We projected lung cancer incidence in Hong Kong from 2020 to 2030 using Bayesian age-period-cohort analysis with an integrated nested Laplace approximation. We decomposed changes in the number of lung cancer cases into population growth, population aging, and epidemiologic changes. From 1985 to 2019, the number of lung cancer incident cases in Hong Kong continued to rise, yet the age-standardized incidence rates have declined for both sexes while have fluctuated for females over the past two decades. The overall annual percentage change from 1985 to 2019 was -2.29 (95% CI, -2.53 to -2.05) for males and -0.86 (95% CI, -1.06 to -0.65) for females. Age-specific annual percentages for both sexes showed a decreasing trend in all age groups and were more pronounced for females older than 65 years and males younger than 65 years. Period effects for both sexes showed a similar monotonic downward pattern, with the downward trend slowing for females after 2000. The cohort effect declined monotonically for males and started to plateau for females after the 1945 birth cohort. It was projected that the incident cases of lung cancer in Hong Kong would continue to increase, with 4,435 male cases and 3,561 female cases in 2030. Demographic decomposition suggested that population growth and population aging play an important role in the change of lung cancer cases. Much progress has been made in reducing the incidence of lung cancer in Hong Kong, but this has been offset b y demographic changes that will continue to increase the incident cases of lung cancer in Hong Kong, especially among females. There is an urgent need for continued public health policies and clinical programs for risk factor control and necessary screening. PMID:35018232 | PMC:PMC8727798 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-187 exerts tumor-suppressing functions in osteosarcoma by targeting ZEB2 [Retraction]

xlomafota13 shared this article with you from Inoreader MicroRNA-187 exerts tumor-suppressing functions in osteosarcoma by targeting ZEB2 [Retraction] Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6218. eCollection 2021. ABSTRACT [This retracts the article on p. 2859 in vol. 6, PMID: 28042505.]. PMID:35018254 | PMC:PMC8727813 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Advanced hepatocellular carcinoma treated by transcatheter arterial chemoembolization with drug-eluting beads plus lenvatinib versus sorafenib, a propensity score matching retrospective study

xlomafota13 shared this article with you from Inoreader Advanced hepatocellular carcinoma treated by transcatheter arterial chemoembolization with drug-eluting beads plus lenvatinib versus sorafenib, a propensity score matching retrospective study Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6107-6118. eCollection 2021. ABSTRACT Recently, a prospective randomized study suggested that transcatheter arterial chemoembolization (TACE) plus lenvatinib, as opposed to TACE plus sorafenib, was an effective and promising treatment for patients with advanced hepatocellular carcinoma (HCC) having portal vein thrombus (PVTT) and large tumor burden. However, no propensity score matching retrospective studies on TACE with drug-eluting beads (DEB-TACE) plus lenvatinib (DEB-TACE+LEN) versus DEB-TACE plus sorafenib (DEB-TACE+SOR) for advanced HCC has been reported to date. The medical records of consecutive patients with advanced HCC who underwent DEB-TACE+LEN or DEB-TACE+SOR between January 2017 and December 2020 were retrospectively reviewed. Mutation genes (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by whole-exome sequencing (WES). Adverse events (AEs), objective response rate (ORR), disease c ontrol rate (DCR), overall survival (OS) and time to progression (TTP) were compared between patients who underwent DEB-TACE+LEN and DEB-TACE+SOR. In total, 150 patients were enrolled in this study. The DEB-TACE+LEN group (n=50) showed significantly better ORR (64.0% vs. 33.3%; P=0.008), OS (hazard ratio [HR]=0.63, 95% confidence interval (CI): 0.41-0.98; P=0.043), and TTP (HR=0.65, 95% CI: 0.45-0.94; P=0.023) than that in the DEB-TACE+SOR group (n=100). Subgroup analyses showed that in patients with portal vein tumor thrombus (PVTT), OS and TTP were significantly longer in the DEB-TACE+LEN group than in the DEB-TACE+SOR group (HR=0.59, 95% CI: 0.36-0.98; P=0.043; HR=0.89, 95% CI: 0.35-2.29; P=0.035). In patients with FGF21 amplification, OS was also significantly longer in the DEB-TACE+LEN group than that in the DEB-TACE+SOR group (HR=0.19, 95% CI: 0.06-0.66; P=0.003). The patients in DEB-TACE+LEN group had a significantly lower incidence o f hand-foot skin reaction (32.0% vs. 49.0%; P=0.048), but a higher incidence of proteinuria (26.0% vs. 10.0%; P=0.010) than that in the DEB-TACE+SOR group. In conclusion, DEB-TACE+LEN conferred better ORR, OS and TTP than did DEB-TACE+SOR in patients with advanced HCC, especially those with PVTT and FGF21 amplification, with acceptable AEs; thus making it a superior treatment modality for these patients. PMID:35018245 | PMC:PMC8727795 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer

xlomafota13 shared this article with you from Inoreader Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):5992-6003. eCollection 2021. ABSTRACT Venous thromboembolism is the most common complication and the secondary cause of death in pancreatic cancer. Moreover, the hypercoagulable state induces microcirculation dysfunction, acidosis and hypoxia, and further enhances tumor immune evasion, tumor growth and metastasis. Numerous studies have revealed that patients with malignant tumors have high levels of IL-6, which stimulates hepatocytes to synthesize thrombopoietin, causing an increase in platelets. This study found that the concentration of IL-6 in pancreatic cancer patient sera was higher than that in healthy donors, while pancreatic cancer cells had low expression levels of IL-6, which was different from other types of cancer. This contradictory result prompted us to uncover the underlying mechanism. Our data revealed that pancreatic cancer enhanced IL-6 production in fibroblasts via the Jagged/Notch axis, while IL-6 further elevated Jagged-1/2 expression in a paracrine positive feedback loop in pancreatic cancer. Inhibition experiments and RNAi studies demonstrated that IL-6-induced Jagged-1/2 production in pancreatic cancer depended on STAT3 and that Jagged-1/2 enhanced IL-6 mRNA expression in HSFs through the NF-κB pathway. Finally, the animal study showed that knockdown of Jagged-1/2 or blockade of the Jagged/Notch pathway by Nirogacestat could alleviate pancreatic cancer-induced hypercoagulability. Accordingly, our findings clarified the key role of the Jagged/Notch/IL-6/STAT3 feedback loop in the development of a hypercoagulable state in pancreatic cancer, which also provides new therapeutic strategies for pancreatic cancer patients who suffer from hypercoagulability. PMID:35018238 | PMC:PMC8727799 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Therapeutic opportunities in cancer therapy: targeting the p53-MDM2/MDMX interactions

xlomafota13 shared this article with you from Inoreader Therapeutic opportunities in cancer therapy: targeting the p53-MDM2/MDMX interactions Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):5762-5781. eCollection 2021. ABSTRACT Ubiquitination is a key enzymatic post-translational modification that influences p53 stability and function. p53 protein regulates the expression of MDM2 (mouse double-minute 2 protein) E3 ligase and MDMX (double-minute 4 protein), through proteasome-based degradation. Exploration of targeting the ubiquitination pathway offers a potentially promising strategy for precision therapy in a variety of cancers. The p53-MDM2-MDMX pathway provides multiple molecular targets for small molecule screening as potential therapies for wild-type p53. As a result of its effect on molecular carcinogenesis, a personalized therapeutic approach based on the wild-type and mutant p53 protein is desirable. We highlighted the implications of p53 mutations in cancer, p53 ubiquitination mechanistic details, targeting p53-MDM2/MDMX interactions, significant discoveries related to MDM2 inh ibitor drug development, MDM2 and MDMX dual target inhibitors, and clinical trials with p53-MDM2/MDMX-targeted drugs. We also investigated potential therapeutic repurposing of selective estrogen receptor modulators (SERMs) in targeting p53-MDM2/MDMX interactions. Molecular docking studies of SERMs were performed utilizing the solved structures of the p53/MDM2/MDMX proteins. These studies identified ormeloxifene as a potential dual inhibitor of p53/MDM2/MDMX interaction, suggesting that repurposing SERMs for dual targeting of p53/MDM2 and p53/MDMX interactions is an attractive strategy for targeting wild-type p53 tumors and warrants further preclinical research. PMID:35018225 | PMC:PMC8727821 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.