Natural killer cells: of-the-shelf cytotherapy for cancer immunosurveillance

xlomafota13 shared this article with you from Inoreader Natural killer cells: of-the-shelf cytotherapy for cancer immunosurveillance Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1770-1791. eCollection 2021. ABSTRACT Natural killer (NK) cells are advantaged innate cytotoxic lymphocytes with characteristics of tumor immunosurveillance and microorganism elimination. Distinguish from the adaptive T and B lymphocytes, the autologous or allogeneic NK cells efficaciously fulfil the function of combating transformed hematological malignancies and metastatic solid tumors via the proverbial mechanisms including direct cytolytic effect and antibody-dependent cell-mediated cytotoxicity (ADCC) as well as paracrine effects dispense with antigen presentation. Herein, we review the candidate sources (e.g., peripheral blood, umbilical cord blood, placental blood, cell lines and stem cells) for large-scale and clinical-grade NK cell manufacturing, ex vivo cultivation (feeder-, cytokine cocktail- or physicochemical irritation-dependent strategies) for NK cell persistence and activation. Further more, we also figure out the promising prospects as well as the accompanied challenges of NK cell- or chimeric antigen receptor-transduced NK (CAR-NK) cell-based adoptive immunotherapy in standardizations for industrialized preparation and clinical practices. PMID:33948388 | PMC:PMC8085843 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Costunolide suppresses melanoma growth via the AKT/mTOR pathway in vitro and in vivo

xlomafota13 shared this article with you from Inoreader Costunolide suppresses melanoma growth via the AKT/mTOR pathway <em>in vitro</em> and <em>in vivo</em> Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1410-1427. eCollection 2021. ABSTRACT Melanoma is the most common type of skin cancer and its incidence is rapidly increasing. AKT, and its related signaling pathways, are highly activated in many cancers including lung, colon, and esophageal cancers. Costunolide (CTD) is a sesquiterpene lactone that has been reported to possess neuroprotective, anti-inflammatory, and anti-cancer properties. However, the target and mechanism underlying its efficacy in melanoma have not been identified. In this study, we elucidated the mechanism behind the anti-cancer effect of CTD in melanoma in vitro and in vivo by identifying CTD as an AKT inhibitor. We first verified that p-AKT and AKT are highly expressed in melanoma patient tissues and cell lines. CTD significantly inhibited the proliferation, migration, and invasion of melanoma cells including SK-MEL-5, SK-MEL-28, and A375 that are overexpressed p- AKT and AKT proteins. We investigated the mechanism of CTD using a computational docking modeling, pull-down, and site directed mutagenesis assay. CTD directly bound to AKT thereby arresting cell cycle at the G1 phase, and inducing the apoptosis of melanoma cells. In addition, CTD regulated the G1 phase and apoptosis biomarkers, and inhibited the expression of AKT/mTOR/GSK3b/p70S6K/4EBP cascade proteins. After reducing AKT expression in melanoma cells, cell growth was significantly decreased and CTD did not showed further inhibitory effects. Furthermore, CTD administration suppressed tumor growth and weight in cell-derived xenograft mice models in vivo without body weight loss and inhibited the expression of Ki-67, p-AKT, and p70S6K in tumor tissues. In summary, our study implied that CTD inhibited melanoma progression in vitro and in vivo. In this study, we reported that CTD could affect melanoma growth by targeting AKT. Therefore, CTD has considerable potentia l as a drug for melanoma therapy. PMID:33948365 | PMC:PMC8085867 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways

xlomafota13 shared this article with you from Inoreader AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1185-1205. eCollection 2021. ABSTRACT This study aimed to investigate the interaction of A-kinase-interacting protein 1 (AKIP1) with C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, and their effects on regulating glioblastoma multiforme (GBM) malignant behaviors. AKIP1 expression was modified by pcDNA and pGPH1 vectors in U-87 MG and U-251 MG cells. Subsequently, multiple compensative experiments were conducted via adding CXCL1, CXCL2 and CXCL8 in the pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells, respectively. Furthermore, AKIP1, CXCL1/2/8 expressions in 10 GBM and 10 low-grade glioma (LGG) tumor samples were detected. AKIP1 was elevated in various GBM cell lines compared to normal human astrocytes. AKIP1 overexpression promoted U-87 MG and U-251 MG cell proliferation and invasion while inhibited apoptosis; and it enhanced chemoresistance to temozolomide (but not cisplatin) and radiation resistance; then AKIP1 knockdown showed the opposite effects. Meanwhile, AKIP1 positively regulated CXCL1/2/8, NF-κB pathway, AKT pathway and PD-L1 expression. Further multiple compensative experiments uncovered that CXCL1 and CXCL8 promoted proliferation, invasion, chemoradiation resistance, NF-κB pathway, AKT pathway and PD-L1 expression in U-87 MG and U-251 MG cells, also in pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells; although CXCL2 exhibited similar treads, but its effect was much weaker. Besides, NF-κB pathway inhibitor and AKT pathway inhibitor attenuated the effect of CXCL1&CXCL8 on promoting GBM cell malignant behaviors. Clinically AKIP1 and CXCL1/8 were elevated in GBM compared to LGG tumor samples, and they were inter-correlated. AKIP1 promotes GBM viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways. PMID:33948353 | PMC:PMC8085855 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

LncRNAs link cancer stemness to therapy resistance

xlomafota13 shared this article with you from Inoreader LncRNAs link cancer stemness to therapy resistance Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1051-1068. eCollection 2021. ABSTRACT Cancer stem cells (CSCs) are a cellular subpopulation accelerating cancer cell growth, invasion and metastasis and survival. After chemoradiotherapy, CSCs are enriched because of their survival advantages and lead to tumor relapse and metastasis. Elimination of CSCs is critically important for the radical treatment of human cancers. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides and have no protein-coding potential. Aberrant expressions of lncRNAs are associated with human diseases including cancer. LncRNAs function as cancer biomarkers, prognostic factors and therapeutic targets. They induce cancer stemness by chromatin modification, transcriptional regulation or post-transcriptional regulation of target genes as a sponge or through assembling a scaffold complex. Several factors caused aberrant expressions of lncRNAs in CSCs such a s genes mutations, epigenetic alteration and environmental stimuli. Targeting of lncRNAs has been demonstrated to significantly reverse the chemoradioresistance of CSCs. In this review, we have summarized the progress of studies regarding lncRNAs-mediated therapy resistance of CSCs and clarified the molecular mechanisms. Furthermore, we have for the first time analyzed the influences of lncRNAs on cell metabolism and emphasized the effect of tumor microenvironment on lncRNAs functions in CSCs. Overall, the thorough understanding of the association of lncRNAs and CSCs would contribute to the reversal of therapy resistance. PMID:33948345 | PMC:PMC8085841 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Establishment and verification of prognostic model for gastric cancer based on autophagy-related genes

xlomafota13 shared this article with you from Inoreader Establishment and verification of prognostic model for gastric cancer based on autophagy-related genes Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1335-1346. eCollection 2021. ABSTRACT Autophagy played a significant role in the development of cancer. In this study, we explored the value of autophagy-associated genes in gastric cancer. RNA sequencing and clinical information containing 375 gastric cancer and 32 normal tissues were gathered from the TCGA portal. Then we stochastically allocated the autophagy-associated genes (AAGs) to training and testing groups. Next, we screened the discrepantly expressed AAGs and the prognostic AAGs by Cox regression analysis and Lasso regression analysis. Afterwards, we structured the model by using the prognostic AAGs and plotted Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves to verify the performance of models in both groups. Besides, we utilized Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecul ar mechanisms of AAGs in gastric cancer. Finally, we demonstrated discrepant expression of AAGs within gastric cancer and non-tumor tissues at protein level with immunohistochemistry. 28 discrepantly expressed AAGs were screened from the TCGA database which contained 375 gastric cancer and 32 non-tumor samples. Cox and Lasso regression analyses were performed in training group and then we got 5 prognostic AAGs to establish the prognostic model. The patients who had high risk possessed worse overall survival (OS) both in training group (5-year OS, 47.6% vs 23.1%; P < 0.0001) and test group (5-year OS, 49.2% vs 0%, P=0.019). The proportion under ROC curves (AUC) were significant both in training group and test group (5-year AUC, 0.736 vs 0.809). Through this study, we constructed a model for gastric cancer patients which may provide individual treatment and superior prognosis. PMID:33948361 | PMC:PMC8085875 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The clinical significance of fHIT in migraine patient without vertigo symptom

xlomafota13 shared this article with you from Inoreader Correction to: The clinical significance of fHIT in migraine patient without vertigo symptom 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. 2021 May 5. doi: 10.1007/s00405-021-06852-z. Online ahead of print. NO ABSTRACT PMID:33950357 | DOI:10.1007/s00405-021-06852-z View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Soluble P-selectin levels in patients with obstructive sleep apnea: a systematic review and meta-analysis

xlomafota13 shared this article with you from Inoreader Soluble P-selectin levels in patients with obstructive sleep apnea: a systematic review and meta-analysis 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. 2021 May 5. doi: 10.1007/s00405-021-06831-4. Online ahead of print. ABSTRACT PURPOSE: Obstructive sleep apnea (OSA) patients are at increased risk for cardiovascular disease, stroke, atherosclerosis, hypertension, and venous thromboembolism. Elevated soluble P-selectin (sP-selectin) levels are also associated with increased risk of above diseases. But whether sP-selectin levels in OSA patients are higher than their counterparts remain unclear, since previous studies yielded inconsistent results. Therefore, a meta-analysis is warranted. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies. Studies were included if they reported sP-selectin levels of both OSA patients and non-OSA controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to determine the effect sizes. RESULTS: Nine eligible studies were fin ally evaluated. When all the studies were pooled, sP-selectin levels in OSA patients were significantly higher than that in controls (SMD = 0.54, 95% CI 0.29-0.78, I2 = 66%, p < 0.0001). In the subgroup analysis based on BMI matched groups, sP-selectin levels were significantly higher in OSA patients than that in controls (SMD = 0.52, 95% CI 0.27-0.76, I2 = 23%, p < 0.0001). In the subgroup analysis stratified by blood source, either serum sP-selectin levels or plasma sP-selectin levels in OSA patients were higher than that in controls. Moderate-to-severe OSA patients had significant higher sP-selectin levels (SMD = 0.80, 95% CI 0.45-1.15, I2 = 67%, p < 0.00001), while mild OSA patients showed no significant difference with controls. CONCLUSION: The pooled results reveal that OSA patients have higher sP-selectin levels than non-OSA controls. This conclusion remains unaltered in all subgroups other than the subgroup of mild OSA patients . Additional studies are warranted to better identify the role of sP-selectin as a potential biomarker in OSA patients. PMID:33950356 | DOI:10.1007/s00405-021-06831-4 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The mini incision approach to the facial artery as a recipient vessel in head and neck reconstruction

xlomafota13 shared this article with you from Inoreader The mini incision approach to the facial artery as a recipient vessel in head and neck reconstruction Via Journal of plastic, reconstructive & aesthetic surgery : JPRAS J Plast Reconstr Aesthet Surg. 2021 Apr 18:S1748-6815(21)00173-X. doi: 10.1016/j.bjps.2021.03.072. Online ahead of print. NO ABSTRACT PMID:33941471 | DOI:10.1016/j.bjps.2021.03.072 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anterior tibial artery injury is not the contraindication of medial plantar flap: digital subtraction angiography evidence and clinical application

xlomafota13 shared this article with you from Inoreader Anterior tibial artery injury is not the contraindication of medial plantar flap: digital subtraction angiography evidence and clinical application Via Journal of plastic, reconstructive & aesthetic surgery : JPRAS J Plast Reconstr Aesthet Surg. 2021 Mar 30:S1748-6815(21)00144-3. doi: 10.1016/j.bjps.2021.03.054. Online ahead of print. ABSTRACT The medial plantar artery (MPA) is often sacrificed as the vascular pedicle of the medial plantar flap (MPF). However, for patients with ankle soft tissue defect caused by traffic accident, the anterior tibial artery (ATA) could be damaged and the blood supply of the distal foot would only come from the MPA and the lateral plantar artery (LPA). In this case, sacrificing the MPA for the MPF means that the LPA will become the mainly source of blood supply of the distal foot. Whether the blood supply of the distal foot is adequately guaranteed remains to be discussed. A total of seven patients with ankle soft tissue defect and ATA injury were enrolled in the study. The digital subtraction angiography (DSA) was performed to observe the hemodynamics of the ipsilateral foot. The MPF was harvested only when the fo ot arterial network consisting of the MPA, the LPA, the deep plantar arch, and the deep plantar artery of DPA, and the blood redistribution existed. DSA results showed the blood from the posterior tibial artery was redistributed to the ipsilateral foot and the MPA is not the dominant artery in the foot. Seven MPFs were harvested, and all flaps survived completely. No complications, such as pain, ulcer, and necrosis, occurred in the ipsilateral toes. The DSA could accurately and intuitively evaluate the hemodynamics of foot in patients with ATA injury. The DSA data and clinical practice proved that the ATA injury is not the contraindication of the MPF. PMID:33941474 | DOI:10.1016/j.bjps.2021.03.054 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Revisiting the unrepaired unilateral cleft lip and nasal deformity using 3D surface image analysis: A data-driven model and its implications

xlomafota13 shared this article with you from Inoreader Revisiting the unrepaired unilateral cleft lip and nasal deformity using 3D surface image analysis: A data-driven model and its implications Via Journal of plastic, reconstructive & aesthetic surgery : JPRAS J Plast Reconstr Aesthet Surg. 2021 Mar 30:S1748-6815(21)00116-9. doi: 10.1016/j.bjps.2021.03.026. Online ahead of print. ABSTRACT BACKGROUND: Current descriptions of the unilateral cleft lip and nasal deformity (uCLND) are based upon limited sample sets and subjective observations. While those descriptions are inconsistent and contradictory, theoretical models, including Hogan's "tilted tripod" and Fisher's "nasal arch forms", have never been tested. Given that favorable outcomes of treatment remain elusive, detailed study of the deformity is critical in devising better treatments. The purpose of this study was to develop a data-driven three-dimensional (3D) model of uCLND that spans the spectrum of presentation and involves a pervasive underlying mechanism. METHODS: We studied 3D images of 100 infants with unrepaired cleft lip at 6 months of age. Objective assessment included the landmark positions, anthropometric dimensions, a nd shape-based measures. Cleft severity was stratified by the lateral displacement of subnasale, so that a model could be developed using linear regression. RESULTS: With progressive deviation of subnasale, the non-cleft alar base moved lateral, the cleft alar base was left posterior, and the nasal dorsum followed the caudal septum (deviating towards the non-cleft side). The "twist" resulted in opposing cleft alar dome collapse, non-cleft alar ring constriction (the non-cleft nasal sill narrowed, lateral genu rose, and alar-cheek junction became more acute), and displacement of the philtrum from midline. CONCLUSIONS: Our study not only supports theoretical models of uCLND but also clarifies vectors of change and reveals significant non-cleft side alterations. On the basis of our findings, the objectives of treatment should involve centralization of the columella and philtrum and rebalancing the nose by untwisting the orthogonal displacement of the alar bases. PMID: 33941472 | DOI:10.1016/j.bjps.2021.03.026 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Rare Laryngeal Presentation of Stevens‐Johnson Syndrome

xlomafota13 shared this article with you from Inoreader A Rare Laryngeal Presentation of Stevens‐Johnson Syndrome Via The Laryngoscope Stevens‐Johnson syndrome (SJS) is a rare but severe mucocutaneous epidermolysis commonly triggered by medications. SJS is characterized by mucocutaneous lesions of the trunk, face, and limbs, as well as the oral cavity, gastrointestinal tract, and respiratory tract. Although uncommon, laryngeal involvement in SJS can lead to severe respiratory, phonatory and deglutitive complications. Providers caring for patients with SJS should maintain a high index of suspicion for laryngeal involvement and low threshold to solicit Otolaryngology consultation. Laryngeal complications can be more expediently managed when anticipated early in the course of disease. Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.