Chronic stress promotes an immunologic inflammatory state and head and neck cancer growth in a humanized murine model

xlomafota13 shared this article with you from Inoreader Chronic stress promotes an immunologic inflammatory state and head and neck cancer growth in a humanized murine model Via Head & Neck Abstract Background Despite the importance of immune response and environmental stress on head and neck cancer (HNC) outcomes, no current pre-clinical stress model includes a humanized immune system. Methods We investigated the effects of chronic stress induced by social isolation on tumor growth and human immune response in subcutaneous HNC tumors grown in NSG-SGM3 mice engrafted with a human immune system. Results Tumor growth (p < 0.0001) and lung metastases (p = 0.035) were increased in socially isolated versus control animals. Chronic stress increased intra-tumoral CD4+ T-cell infiltrate (p = 0.005), plasma SDF-1 (p < 0.0001) expression, and led to tumor cell dedifferentiation toward a cancer stem cell phenotype (CD44+/ALDHhigh, p = 0.025). Conclusions Chronic stress induced immunophenotypic changes, increased tumor growth, and metastasis in HNC in a murine model with a humanized immune system. This model system may provide further insight into the immunologic and oncologic impact of chronic stress on patients with HNC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Robotic‐Assisted Partial Cystectomy for Muscle Invasive Bladder Cancer: Contemporary Experience

xlomafota13 shared this article with you from Inoreader Robotic‐Assisted Partial Cystectomy for Muscle Invasive Bladder Cancer: Contemporary Experience Via The International Journal of Medical Robotics and Computer Assisted Surgery Abstract Objective To report our contemporary experience with robotic-assisted partial cystectomy (RAPC) for muscle invasive bladder cancer Methods This is a retrospective review of patients who underwent robotic-assisted partial cystectomy with us between 2013 and 2020 and provided ≥ 12 months of follow up. Results and limitations: The median operative time for our 35 patients was 190 min (Interquartile range (IQR) 155–280). Four patients developed grade 3 or higher complications (ileus, pneumonia, and urethral stricture). At 12 months follow-up, the median IPSS score was 10 (IQR 7-11), and recurrence happened in seven patients (recurrence-free survival 80%). Five of the patients who developed recurrence died because of their disease, and two other patients died of causes unrelated to their cancer. Conclusions We describe our technique, functional outcomes, and short-term follow up results in highly selected patients with muscle-invasive bladder cancer treated with RAPC. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Concomitance or consequence? Stevens-Johnson syndrome in COVID-19: A case report

xlomafota13 shared this article with you from Inoreader Concomitance or consequence? Stevens-Johnson syndrome in COVID-19: A case report Via Experimental and therapeutic medicine Exp Ther Med. 2022 Apr;23(4):257. doi: 10.3892/etm.2022.11182. Epub 2022 Feb 2. ABSTRACT The novel coronavirus infection has been, and still is, a pressing medical problem with a catastrophic effect, not only from a medical point of view, but also from an economic and social one. The cutaneous manifestations of the disease have a diverse morphology and can signal the presence of the infection. The present article reports the case of a 77-year-old male patient admitted at The Sf. Parascheva Clinical Hospital of Infectious Diseases in Iasi (Romania) after testing positive for SARS CoV-2 infection. Initially, the patient presented a pruriginous generalized maculopapular-erythematous eruption with a tendency towards confluence, peri-oro-nasal meliceric crusts and desquamation of the skin on the third anterosuperior and posterior thorax, scalp and forehead, which was accompanied by low back pain, headache and orbital pain. The suspicion of Stevens-Johnson syndrome (SJS) was raised, and treatment was given according to the recommendation of the hospital dermatologist. This association raises multiple questions regarding whether SJS is a cutaneous manifestation of COVID-19 or if there was a concomitance between the viral infection and the immune reaction. The combination of SJS and COVID-19 can have a fatal outcome if not recognized and promptly treated. To our knowledge, this is the first case of SJS in a patient diagnosed with SARS CoV-2 infection in Romania. PMID:35261629 | PMC:PMC8855504 | DOI:10.3892/etm.2022.11182 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cofilin-1 as a potential biomarker for Mycobacterium tuberculosis infection

xlomafota13 shared this article with you from Inoreader Cofilin-1 as a potential biomarker for <em>Mycobacterium tuberculosis</em> infection Via Experimental and therapeutic medicine Exp Ther Med. 2022 Apr;23(4):253. doi: 10.3892/etm.2022.11178. Epub 2022 Feb 1. ABSTRACT Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tb), is one of the deadliest human infections worldwide. Our previous studies demonstrated cofilin-1 (CFL1) expression was significantly increased in exosomes from Mycobacterium avium (M. avium)-infected macrophages. The expression of CFL1 protein in M. tb infected hosts was investigated in the present study to predict whether CFL1 could have potential as a biomarker for M. tb infection. In the present study, the mRNA and protein expression levels of CFL1 in M. avium-infected macrophages and supernatants were analyzed via reverse transcription-quantitative PCR and western blotting. Furthermore, CFL1 expression in macrophages was knocked down in vivo, and then CFL1 expression levels in M. avium-infected macrophages and supernata nt were detected via western blotting and ELISA. In addition, CFL1 was detected in the peripheral blood mononuclear cells and plasma of patients with TB using western blotting and ELISA. The specificity and sensitivity of CFL1 as a biomarker and the association between TB infection and normal individuals were compared and analyzed using GraphPad Prism 5. CFL1 protein expression levels were significantly increased in M. avium-infected macrophages and supernatant. Meanwhile, CFL1 was upregulated in patients with TB. Bioinformatics statistics indicated the high specificity and sensitivity of CFL1 in patients with TB. Thus, these results suggest that CFL1 may act as a potential biomarker of TB infection. PMID:35261625 | PMC :PMC8855514 | DOI:10.3892/etm.2022.11178 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Serum metabonomics as a diagnostic approach for cancer-related fatigue

xlomafota13 shared this article with you from Inoreader Serum metabonomics as a diagnostic approach for cancer-related fatigue Via Experimental and therapeutic medicine Exp Ther Med. 2022 Apr;23(4):256. doi: 10.3892/etm.2022.11181. Epub 2022 Feb 2. ABSTRACT In the present study, differences in metabolic pathways between patients with and without cancer-related fatigue (CRF) were examined to identify metabolic serum biomarkers of CRF. In this preliminary study, metabolic profiling was applied to analyze the serum samples from 14 patients with CRF and 11 non-CRF individuals (non-fatigue cancer survivors) by ultra-performance liquid chromatography coupled with mass spectrometry. Orthogonal partial least-squares discriminant analysis was adopted to evaluate the differences between the CRF and non-CRF groups. The CRF group was characterized by increases in phosphatidylethanolamine (PE; 18:0/0:0), LysoPE (0:0/20:4 and 0:0/16:0), lysophosphatidylcholine (LysoPC; 20:4, 22:4 and 16:0) and LysoPC/PC, phosphatidylserine (21:0/0:0), glycerophosphocholine and N-docosahexaenoyl γ-aminobutyric acid. Furthermore, de creases in anandamide, uric acid, dihydrouracil, LysoPE (0:0/22:5), 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman, 19(R)-hydroxy-prostaglandin F1α, N-(3α,12α-dihydroxy-5β-cholan-24-oyl)-glycine, ketoleucine, indoxyl sulfate, α-N-phenylacetyl-L-glutamine and 1-linoleoyl-glycerophosphocholine were detected. These data indicate a possible disturbance in the metabolism of phospholipids and adjustments in the endocannabinoid system. The metabonomic approach may be helpful to determine the pathophysiological mechanisms of CRF and the identification of potential biomarkers for the accurate diagnosis of CRF. All clinical data were obtained from the 'Research on the efficacy of traditional Chinese medicine comprehensive intervention in cancer-related fatigue' (TCM-CRF) project. Medical Ethical Approval for TCM-CRF was approved by the Chinese Ethics Committee of Registering Clinical Trials. The approval number for the TCM-CRF study was ChiECRCT-2013038, and the TCM-CRF study wa s completed. PMID:35261628 | PMC:PMC8855500 | DOI:10.3892/etm.2022.11181 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

PBX4 functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the PBX gene family

xlomafota13 shared this article with you from Inoreader PBX4 functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the PBX gene family Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):585-600. eCollection 2022. ABSTRACT Pre-B-cell leukaemia (PBX) is a transcription factor family (PBX1, PBX2, PBX3 and PBX4) that regulates important cellular functions and has been identified to be involved in human cancers. This study aimed to explore the expression of PBX genes and their clinical significance in colorectal cancer (CRC). We analysed the differential expression of PBX genes in CRC vs. normal tissue, using the Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) and ONCOMINE platform (https://www.oncomine.org/). The UALCAN (http://ualcan.path.uab.edu/) interactive OMICS web-server was used to evaluate the epigenetic regulation of PBX genes via their promoter methylation status. We found that only PBX4 was upregulated whereas PBX1 and PBX3 were downregulated (644 tumour vs. 51 normal samples) (P<0.001). The methylation st atus of PBX4 promoter appeared to be decreased (P=1.4e-07) whereas the methylation status of PBX1 and PBX3 promoters was increased (P=3.8e-04 and P=3.2e-07, respectively) in cancer vs. normal samples. To determine the prognostic value of PBXs, we conducted a Kaplan-Meier survival analysis and multivariable COX regression. We observed that high PBX4 expression was associated with increased risk for a worse overall survival (OS) in the TCGA CRC patient cohort (n=639), (HR 1.46, 95% CI 1.14-1.88, P=0.003) adjusted for age, gender, tumour location and metastases. We conducted in vitro gene expression modulation experiments to investigate the impact of PBX4 overexpression in CRC cell (HCT116) growth. Additionally, we evaluated the RNA expression of epithelial-mesenchymal transition (EMT) and angiogenesis markers. In vitro studies showed that PBX4 overexpression increased CRC cell proliferation (P<0.001) and upregulated the expres sion of EMT markers VIM, CDH1, CDH2, ZEB1, SNAI1 (P<0.05) and angiomarker VEGFA (P<0.0001). Lastly, through the Cistrome data browser (http://dbtoolkit.cistrome.org/) we investigated putative transcriptional regulators and we performed gene set enrichment analysis in Enrichr server (https://maayanlab.cloud/Enrichr/) to identify related biological processes. Nineteen factors were identified to be putative regulators of PBX4 and gene set enrichment analysis showed that biological processes related to cell cycle and cell proliferation were enriched (GO:0051726: CDK8, JUN, JUND, and IRF1, P=0.001). In conclusion, our study identified PBX4 as a potential novel oncopromoter in CRC and its overexpression was found to be associated with increased risk for worse survival rate. PMID:35261789 | PMC:PMC8899996 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Semaphorin 4C promotes motility and immunosuppressive activity of cancer cells via CRMP3 and PD-L1

xlomafota13 shared this article with you from Inoreader Semaphorin 4C promotes motility and immunosuppressive activity of cancer cells via CRMP3 and PD-L1 Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):713-728. eCollection 2022. ABSTRACT Semaphorins (SEMAs) are membrane-bound or soluble proteins that participate in organ development and cancer progression, however, the detailed role of SEMAs in carcinogenesis is not fully elucidated yet. Our in silico analysis showed among the differentially expressed SEMAs in colon cancer tissues, patients with higher SEMA4C expression tumors had worse survival. The migration and invasion of the HCT116 and CT26 colon cancer cells were significantly suppressed by SEMA4C neutralizing antibody treatment; while enhanced by ectopic expression of SEMA4C. Subsequently, RNA sequencing study revealed microtubule polymerization- and nucleation-related genes are highly enriched in SEMA4C overexpression HCT116 cells. Western blotting showed the negative correlation between the levels of SEMA4C expression and tubulin acetylation. Mechanistic study showed SEMA4C interacte d with and stabilized collapsin response mediator protein 3 (CRMP3), a novel deacetylase, to increase α-tubulin deacetylation and cell motility, which could be effectively attenuated after HDAC inhibitors treatment. We also found that a tumor-suppressive miRNA let-7b can target SEMA4C and act synergistically with SEMA4C neutralizing antibody to suppress the motility of colon cancer cells. In addition, blockade of SEMA4C could attenuate the expression of program death ligand 1 (PD-L1). Collectively, our results highlight that SEMA4C may promote colon cancer progression through modulating CRMP3-mediated tubulin deacetylation and PD-L1-mediated immunosuppression. PMID:35261797 | PMC:PMC8899990 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma

xlomafota13 shared this article with you from Inoreader Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):562-573. eCollection 2022. ABSTRACT In this study, we aimed to investigate how homologous recombinant (HR)-related genomic instability is involved in ionizing radiation (IR)-induced thymic lymphoma in mice. We divided five-week-old Rosa26 Direct Repeat-GFP (RaDR-GFP) transgenic mice into non-IR control and IR groups and exposed the mice in the IR group to a 7.2 Gy dose of γ-rays, delivered in 1.8 Gy fractions, once a week for four weeks. We then estimated mouse survival and recorded their body, thymus, and spleen weights. The frequency of HR events in the chromosomes of the thymus, bone marrow, and spleen cells and the phenotype of thymic lymphoma cells were analyzed using fluorescence-activated cell sorting (FACS). We found that most mice in the IR group developed thymic lymphoma, their survival rate decreasing to 20% after 180 days of IR exposure, whereas no mice died in the non-IR control group un til day 400. The thymus and spleen weighed significantly more in the IR-4-month group than that in the non-IR group; however, we observed no significant differences between the body weights of the control and IR mice. FACS analysis indicated that the frequency of HR events significantly increased at two and four months after the last IR dose in the bone marrow and thymus cells, but not in the spleen cells of RaDR-GFP transgenic mice, suggesting that recombinant cells accumulated in the thymus upon IR exposure. This suggests that IR induces genome instability, revealed as increased HR, that drives the development of thymic lymphoma. Additionally, phenotypic analysis of lymphoma cells showed an increase in the CD4-/CD8+ (CD8SP) cell population and a decrease in the CD4+/CD8- (CD4SP) cell population in the IR-4-month group compared to that in the non-IR group, indicating that IR induces an aberrant cell phenotype characteristic of lymphoma. I n conclusion, we observed a significant increase in HR events and abnormal phenotype in thymic lymphoma cells at two and four months after IR exposure in both the thymus and bone marrow tissues, suggesting that genomic instability is involved in the early stages of thymic lymphomagenesis. Our study indicates that HR-visualizing RaDR-GFP transgenic mice can help explore the links between the molecular mechanisms of genome instability and IR-induced tumorigenesis. PMID:35261787 | PMC:PMC8899999 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Negative correlations of psychological distress with quality of life and immunotherapy efficacy in patients with advanced NSCLC

xlomafota13 shared this article with you from Inoreader Negative correlations of psychological distress with quality of life and immunotherapy efficacy in patients with advanced NSCLC Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):805-815. eCollection 2022. ABSTRACT To evaluate the relationships between psychological distress and immunotherapy efficacy, adverse reactions and quality of life scores in patients with advanced non-small cell lung cancer (NSCLC). A total of 104 NSCLC patients who received 4-6 cycles of standard immunotherapy were enrolled and evaluated with the Distress Thermometer (DT) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The aim was to analyze the correlation between psychological distress and quality of life and to analyze whether psychological distress affects the efficacy of and adverse reactions to immunotherapy. The objective response rate (ORR) and disease control rate (DCR) of the psychological distress group were 6% and 50%, respectively, and those of the no psychological distress group were 18.5% and 83.3%, respectively. The differen ces were statistically significant (χ2=14.131, P<0.05). The progression-free survival (PFS) of advanced NSCLC patients who received comprehensive immunotherapy and had no psychological distress was significantly better than that of the psychological distress group (HR, 0.338; 95% CI, 0.192-0.592; P<0.05). The PFS of advanced NSCLC patients who received immunotherapy combined with chemotherapy in the no psychological distress group was significantly better than that in the psychological distress group (HR, 0.458; 95% CI, 0.296-0.709; P<0.05). Psychological distress in advanced NSCLC patients affects the efficacy of immunotherapy, and psychological distress is negatively correlated with quality of life during immunotherapy. PMID:35261803 | PMC:PMC8899984 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The expression of cancer-testis antigen in ovarian cancer and the development of immunotherapy

xlomafota13 shared this article with you from Inoreader The expression of cancer-testis antigen in ovarian cancer and the development of immunotherapy Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):681-694. eCollection 2022. ABSTRACT Ovarian cancer is a relatively common tumor in women with the highest mortality among female reproductive system tumors. The lack of apparent early symptoms and effective screening strategies often leads to ovarian cancer being diagnosed at an advanced stage. Immunotherapy relying on tumor-associated antigens might improve the treatment of ovarian cancer. Cancer-testis antigens (CTAs) are ideal tumor-associated antigens, and MAGE-A, NY-ESO-1, CT45, and Sp17 are classic CTAs highly expressed in ovarian cancer. Here, we review the research on CTAs in ovarian cancer, including prognostic value and advances in immunotherapy, all of which are essential for developing a theoretical basis for targeted therapy strategies. PMID:35261795 | PMC:PMC8899981 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ONC206 has anti-tumorigenic effects in human ovarian cancer cells and in a transgenic mouse model of high-grade serous ovarian cancer

xlomafota13 shared this article with you from Inoreader ONC206 has anti-tumorigenic effects in human ovarian cancer cells and in a transgenic mouse model of high-grade serous ovarian cancer Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):521-536. eCollection 2022. ABSTRACT ONC206, a dopamine receptor D2 (DRD2) antagonist and imipridone, is a chemically modified derivative of ONC201. Recently, ONC206 and other imipridones were identified as activators of the mitochondrial protease ClpP, inducing downstream pathways that allow them to selectively target cancer cells. Clinical trials showed that ONC201, the first in class imipridone, was well tolerated and exhibited tumor regression in some solid tumors. Our goal was to evaluate the effect of ONC206 on cell proliferation and tumor growth in ovarian cancer cell lines and in a transgenic mouse model of high grade serous ovarian cancer (KpB model). ONC206 was more potent than ONC201 in inhibiting cell proliferation, as evidenced by a 10-fold decrease in IC50 for the SKOV3 and OVCAR5 cell lines. This was accompanied by the results that ONC206 significantly inhibited cellular proliferation, i nduced cell cycle G1 arrest and apoptosis, caused cellular stress, and inhibited adhesion and invasion in vitro. Treatment of obese and non-obese KpB mice with ONC206 elevated Bip and ClpP expression and reduced KI67, BCL-XL and DRD2 expression in the ovarian tumors. Our findings demonstrate that ONC206 has anti-tumorigenic effects in ovarian cancer as previously demonstrated by ONC201 but appears to be as well tolerated and more potent. Thus, ONC206 deserves further evaluation in clinical trials. PMID:35261784 | PMC:PMC8900003 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.