SERMs suppresses the growth of ERalpha positive cervical cancer xenografts through predominant inhibition of extra-nuclear ERalpha expression

xlomafota13 shared this article with you from Inoreader SERMs suppresses the growth of ERalpha positive cervical cancer xenografts through predominant inhibition of extra-nuclear ERalpha expression Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):3335-3353. eCollection 2021. ABSTRACT The role of estrogens and estrogen receptors (ER) in cervical cancer (CC) is not well established. However, epidemiological studies and abundant evidence from genetically engineered mouse models support such hypothesis. In this study, we have addressed estrogen responsiveness in a human CC cell line xenograft mouse model. We assessed the sensitivity of Ethynyl Estradiol (EE), SERMs (fulvestrant, MPP) and a non-SERM (EGCG) to competitively modulate the growth of ERα+ve MS751 CC xenografts. We also checked the agonistic-antagonistic propensity of the above treatments to alter the histology of ovariectomised mouse uterine cervix. Chronic EE treatment encouraged the growth of ERα+ve MS751 CC xenografts, while SERMs and EGCG significantly decreased tumor formation. SERMs were found to inhibit ERα expression, localized within cytoplasmic and mem brane compartments. Conversely, ERα was not inducible and EE administration suppressed the growth of ERα-ve HeLa CC xenografts. SERMs competitively induced atrophic features to uterine cervix, with MPP giving rise to mucinous metaplasia in the ectocervix. We have demonstrated that, estrogen sensitivity mediated through ERα has promoted CC tumorigenesis. This in turn was modulated by SERMs, predominantly through inhibition of extra-nuclear ERα expression. Though, induction of hyper-estrogenic status in the ectocervix, might underrate the utility of SERMs in ERα+ve CC. PMID:34249466 | PMC:PMC8263693 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

HP1BP3 promotes tumor growth and metastasis by upregulating miR-23a to target TRAF5 in esophageal squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader HP1BP3 promotes tumor growth and metastasis by upregulating miR-23a to target TRAF5 in esophageal squamous cell carcinoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):2928-2943. eCollection 2021. ABSTRACT HP1BP3, an ubiquitously expressed nuclear protein belonging to the H1 histone family of proteins, plays an important role in cell growth and viability. Recently, it was reported that HP1BP3 exclusively regulates miRNA biogenesis by enhancing transcriptional miRNA processing. Although HP1BP3 has previously been implicated in common cancer types, the mechanistic functions and effects of HP1BP3 and its role in the prognosis of esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we report that ESCC tissues and cell lines show increased endogenous expression of HP1BP3. Knockdown of HP1BP3 in TE-1 cells significantly inhibited tumor growth and metastasis in vivo emphasizing its role in cell proliferation and invasion. In contrast, overexpression of HP1BP3 significantly enhanced tumor growth and metastasis in Eca-109 cells. Further, we found that HP1BP 3 regulates these functions by upregulating miR-23a, which directly binds to the 3'UTR region of TRAF5 downstream to alter cell survival and proliferation. Our findings describe a role for HP1BP3 in promoting tumor growth and metastasis by upregulating miR-23a to target TRAF5 in esophageal cancer. This study provides novel insights into the potential of targeting miRNAs for therapy and as clinical markers for cancer progression. PMID:34249436 | PMC:PMC8263663 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DLX5 promotes osteosarcoma progression via activation of the NOTCH signaling pathway

xlomafota13 shared this article with you from Inoreader DLX5 promotes osteosarcoma progression via activation of the NOTCH signaling pathway Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):3354-3374. eCollection 2021. ABSTRACT The distal-less (dlx) homeobox transcription factors have been implicated roles in bone development. DLX5, in particular, was shown to play essential roles in osteoblast differentiation by targeting RUNX2, a master transcription factor for bone development. Interestingly, DLX5 has also been shown to play an oncogenic role in lung and other cancers, possibly via regulation of MYC expression. Given its dual roles in bone and cancer, this study aimed to investigate the effect of DLX5 on progression of osteosarcoma (OS), the primary bone cancer that is characterized by abnormal bone formation and osteoblast activity. Expression of DLX5 in OS cell lines was detected by quantitative real-time PCR (qRT-PCR) and western blot (WB). In vitro and in vivo assays were performed to investigate the oncogenic function of DLX5 in OS cells and xenograft models. Luciferase reporter assay was performed to determine the underlying mechanism of DLX5-mediated OS aggressiveness. The results showed that DLX5 was differentially expressed in OS cell lines, with significantly upregulated levels in HOS and MG-63 and relatively low levels in U2OS and 143B cell lines, compared with the normal bone cell line. DLX5 knockdown in HOS and MG-63 cell lines by siRNA inhibited OS cell growth and progression, and induced cell apoptosis and cell cycle changes both in vitro and in vivo. Meanwhile, DLX5 overexpression had the opposite effect on U2OS and 143B cell lines. Notably, a positive correlation between the expression patterns of NOTCH1 and DLX5 was also observed. The expression levels of NICD (NOTCH1 intracellular domain) and HES1 (classical target of NOTCH) were closely associated with DLX5 expression. Whereas knockdown of DLX5 in OS cells resulted in decreased expression of NOTCH1 and reduced cell proliferation and migration, which were rescued by overexpression of NOTCH1. W e further analyzed DLX5 and NOTCH1 genes using JASPAR software and found two potential DLX5 binding sites within the NOTCH1 promoter. Dual-luciferase assay demonstrated that DLX5 specifically activates the NOTCH1 promoter and controls its expression. Taken together, our results support that DLX5 plays an oncogenic role in OS development, which can at least partially, be attributed to activation of the NOTCH signaling pathway. PMID:34249467 | PMC:PMC8263696 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Predicting early recurrence for resected pancreatic ductal adenocarcinoma: a multicenter retrospective study in China

xlomafota13 shared this article with you from Inoreader Predicting early recurrence for resected pancreatic ductal adenocarcinoma: a multicenter retrospective study in China Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):3055-3069. eCollection 2021. ABSTRACT A precise classification of early recurrence (ER) after radical surgery of pancreatic ductal adenocarcinoma (PDAC) has not been standardized. We aim to develop an optimal cut-off based on scientific evidence to distinguish early and late recurrence (LR) for PDAC after radical surgery and develop a predictive model for ER of PDAC. The best threshold for recurrence-free survival (RFS) was assessed with a minimum P-value method, and patients were categorized into ER and LR groups. We used a logistic regression model to assess potential risk factors for ER and develop a predictive model for ER risk. The best threshold between high-risk and intermediate-high-risk groups was identified by using the receiver operating characteristic curve. Among 3,279 patients included, 1,234 (37.6%) experienced ER. The RFS of 9 months is the optimal threshold to distinguish ER an d LR. Univariable and multivariable analysis identified four preoperative risk factors for ER, including larger tumor maximal diameter on computed tomography (CT), enlarged lymph nodes on CT, carbohydrate antigen (CA) 125 > 35 U/ml, and CA19-9 > 235 U/ml. The concordance index (C-index) for the predictive model in the training cohort and the validation cohort was 0.651 (95% confidence interval (CI): 0.624-0.678), and 0.636 (95% CI: 0.593-0.679), respectively, showing promising predictive ability. The high-risk group had a score above 203, and the corresponding risk of ER for this group was 56.7%. An RFS of 9 months is the best threshold to distinguish ER and LR. The model can accurately predict the risk of ER in PDAC after radical resection, and risk grouping can predict the patients who could benefit from upfront surgery. PMID:34249444 | PMC:PMC8263647 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-613 suppresses proliferation, migration and invasion of osteosarcoma by targeting c-MET [Retraction]

xlomafota13 shared this article with you from Inoreader MicroRNA-613 suppresses proliferation, migration and invasion of osteosarcoma by targeting c-MET [Retraction] Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):3375. eCollection 2021. ABSTRACT [This retracts the article on p. 2869 in vol. 6, PMID: 28042506.]. PMID:34249468 | PMC:PMC8263675 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A heptamethine cyanine dye serves as a potential marker for myeloid-derived suppressor cells

xlomafota13 shared this article with you from Inoreader A heptamethine cyanine dye serves as a potential marker for myeloid-derived suppressor cells Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):2853-2866. eCollection 2021. ABSTRACT Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with inhibitory effects on T cell-mediated immune response. MDSCs accumulate under many pathological conditions, including cancers, to avoid anticancer immunity. Unlike mouse MDSCs, common specific surface markers for human MDSCs are not clearly defined, mainly due to the complexity of MDSC subsets. In this study, we investigate specific responses of the infrared dye MHI-148 to MDSCs. Mice bearing 4T1 breast cancer cells were established, and splenocytes were isolated. Flow cytometric analyses demonstrated that MHI-148 was reactive to over 80% of MDSC-specific cells manifesting CD11b+/Gr-1+ acquired from both tumor-bearing mice and naive mice. Cells sorted positive for either CD11b/Gr-1 or MHI-148 were also identical to their counterparts (99.7% and 97.7%, respectively). MHI-148, however, was not reactive to lymphocyte or monocyte populations. To determine whether MHI-148-reactive cells exert inhibitory effects on T cell proliferation, an EdU-based T cell assay was performed. MHI-148 reactive cells significantly reduced T cell proliferation with increased arginase activity and nitrite production. In an attempt to test MHI-148 as a marker for human MDSCs, MHI-148 was specifically reactive to CD11b+/CD33+/CD14- granulocytic MDSCs acquired from selected cancer patients. This study demonstrates that the near-infrared dye MHI-148 specifically reacts to mouse splenocytes with known MDSC-specific markers that have T cell suppressive functions. The dye also selectively binds to a subpopulation of immature myeloid cells acquired from cancer patients. While it is not clear how MHI-148 specifically stains MDSCs, this dye can be a novel tool to detect MDSCs and to predict the prognosis of human cancer p atients. PMID:34249432 | PMC:PMC8263665 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-122 inhibits proliferation and invasion in gastric cancer by targeting CREB1 [Retraction]

xlomafota13 shared this article with you from Inoreader MicroRNA-122 inhibits proliferation and invasion in gastric cancer by targeting CREB1 [Retraction] Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):3376. eCollection 2021. ABSTRACT [This retracts the article on p. 323 in vol. 7, PMID: 28337380.]. PMID:34249469 | PMC:PMC8263659 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel mechanism driving poor-prognostic gastric cancer: overexpression of the transcription factor Kruppel-like factor 16 promotes growth and metastasis of gastric cancer through regulating the Notch pathway

xlomafota13 shared this article with you from Inoreader A novel mechanism driving poor-prognostic gastric cancer: overexpression of the transcription factor Kruppel-like factor 16 promotes growth and metastasis of gastric cancer through regulating the Notch pathway Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):2717-2735. eCollection 2021. ABSTRACT Gastric cancer (GC) is one of the most common malignant tumors worldwide and has high rates of morbidity and mortality. This study investigated the role of Krüppel-like factor 16 (KLF16) in GC. Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to examine the expression of KLF16 in gastric cells and tissues. Gene overexpression and silencing were applied to study the involvement of KLF16 in GC cell growth and metastasis along with its underlying mechanism. The results indicate that KLF16 overexpression is significantly associated with nodal status, distant metastasis, staging, degree of differentiation, vascular invasion, and patient survival. Multivariate Cox proportional hazards regression model analysis revealed that the overexpression of KLF16 is an independent prognostic biomarker of GC. The in vitro study revealed that up-regulated KLF16 accelerates cell growth and metastasis, whereas the inhibition of KLF16 suppresses these cellular activities. The results of an animal study also indicated that the overexpression and silencing of KLF16 accelerate and repress xenograft proliferation and metastasis. Further studies of affected cell growth and metastasis revealed that KLF16 modulates the cell cycle and epithelial-mesenchymal transition through transcriptional regulation of microfibrillar-associated protein 5. Collectively, these results reveal that KLF16 overexpression is a potential prognostic biomarker and therapeutic target for the treatment of GC. PMID:34249424 | PMC:PMC8263687 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Muscle weakness caused by cancer and chemotherapy is associated with loss of motor unit connectivity

xlomafota13 shared this article with you from Inoreader Muscle weakness caused by cancer and chemotherapy is associated with loss of motor unit connectivity Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):2990-3001. eCollection 2021. ABSTRACT Skeletal muscle wasting and weakness caused by cancer and its treatments (known as "cachexia") drastically impair quality of life and worsen survival outcomes in cancer patients. There are currently no approved treatments for cachexia. Hence, further investigation into the causes of cachexia induced by cancer and chemotherapy is warranted. Here, we sought to investigate skeletal muscle wasting, weakness and loss of motor unit function in mice bearing cancers or administered chemotherapeutics. Mice bearing colorectal cancers, including C26, MC38 and HCT116, and mice receiving the chemotherapeutics folfiri and cisplatin were assessed for in vivo and ex vivo muscle force, and for in vivo electrophysiological indices of motor unit connectivity, including compound muscle action potential and motor unit number estimation (MUNE). In vivo and < i>ex vivo muscle force, as well as MUNE were reduced in C26, MC38, HCT116 hosts, and in mice receiving folfiri and cisplatin compared to their respective experimental controls. In addition, MUNE was correlated with muscle force and muscle mass in all experimental conditions, while assessment of neuromuscular junction (NMJ) protein expression and changes in presynaptic morphology suggested that cancer and chemotherapy significantly alter muscle innervation. The present results demonstrate that the loss of motor unit connectivity may contribute to skeletal muscle wasting and weakness that occur with cancer and chemotherapy. PMID:34249440 | PMC:PMC8263661 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The cost of cure: Examining objective and subjective financial toxicity in head and neck cancer survivors

xlomafota13 shared this article with you from Inoreader The cost of cure: Examining objective and subjective financial toxicity in head and neck cancer survivors Via Head & Neck Abstract Background Little is documented regarding objective financial metrics and their impact on subjective financial toxicity in head and neck cancer (HNC) survivors. Methods In a cross-sectional analysis, 71 survivors with available claims data for HNC-specific out-of-pocket expenses (OOPE) completed a survey including patient-reported, subjective financial toxicity outcome tools: the Comprehensive Score for financial Toxicity (COST) and the Financial Distress Questionnaire (FDQ). Results Worse COST scores were significantly associated with lower earnings at survey administration (coefficient = 3.79; 95% CI 2.63–4.95; p < 0.001); loss of earnings after diagnosis (coefficient = 6.03; 95% CI 0.53–11.52; p = 0.032); and greater annual OOPE as a proportion of earnings [log10(Annual OOPE:Earnings at survey): coefficient = −5.66; 95% CI −10.28 to −1.04; p = 0.017]. Similar results were found with FDQ. Conclusion Financial toxicity is associated with particular socioeconomic characteristics which, if understood, would assist the development of pre-treatment screening tools to detect at-risk individuals and intervene early in the HNC cancer survivorship trajectory. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Otolaryngologists Trail Other Specialties in Industry Payments From Dermal Filler Companies

xlomafota13 shared this article with you from Inoreader Otolaryngologists Trail Other Specialties in Industry Payments From Dermal Filler Companies Via The Laryngoscope Objectives/Hypothesis Dermal filler (DF) is a widely used nonsurgical option for facial rejuvenation with a rapidly expanding market. Physician payments by DF industry leaders have yet to be characterized. We sought to investigate trends in physician-industry payments by DF companies over 6 years. Differences in payments based on physician specialty and time were characterized. Study Design Database review. Methods The Open Payments Database was queried from 2013 to 2018. Payments made by the three largest DF companies by market share to otolaryngologists, plastic surgeons, and dermatologists were analyzed. Total dollars paid, number of payments made, type of payments made, and total number of specialists paid were recorded. One-way ANOVA was used for statistical analysis. Results Otolaryngologists, plastic surgeons, and dermatologists received average annual payments of $0.36 million, $6.3 million, and $6.6 million respectively (P < .001). An average of 330 otolaryngologists, 2,128 plastic surgeons, and 5,980 dermatologists were paid annually (P < .001). Accredited speaking arrangements, consulting fees, and royalty/licensing fees comprised the majority of dollars paid to physicians. Conclusions Average physician payment by DF companies exceeds $12 million annually, with otolaryngologists receiving significantly less compared to plastic surgeons and dermatologists. Level of Evidence Not applicable Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.