Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is a severe, but potentially reversible autoimmune encephalitis, dominantly affecting children and young adult women [1]. Approximately 60% of patients with NMDA encephalitis have tumors containing nervous tissue, such as ovarian teratoma [2].
Nonfunctional paragangliomas are perioperatively hemodynamically unstable and prone to lethal complications, making anesthesia a high surgical risk. We report the perioperative management of an unanticipated paraganglioma of the bladder over two surgical procedures. The patient developed a hypertensive crisis during the first intraoperative electrodesiccation of the tumor, and the surgeon stopped the operation and sent intraoperative cryopreservation, which was considered a paraganglioma of the bladder. Postoperative histopathological and immunohistochemical results confirmed the case as a paraganglioma of the bladder. Because of the high risk of continuing the surgery, a second surgery was performed after perfecting the preoperative preparation. The patient’s vital signs were stable during the second surgery and the patient’s prognosis was good after the surgery. An unanticipated intraoperative paraganglioma is a major perioperative challenge for anesthesiologists, and the improvement of its outcome is mainly due to good preoperative preparation, intraoperative hemodynamic monitoring, and the application of rapid, potent, and short-acting vasoactive drugs.
Background and Aims: In recent years, exquisite diagnostic techniques are stringent demands in Medical Laboratory Science (MLS). The reviews discuss ways to improve clinical laboratory techniques under the current level of medical care in China. Materials and Methods: With a focus on China’s current situation and development direction of clinical detection technology, journal literature was reviewed; reforms in the educational concepts were studied. Herein, reforms in the management practices of clinical medical testing departments as well as the development and production status of medical testing instruments are discussed. Results: Medical schools should change the educational concept from the traditional “indoctrination” teaching method to a diversified teaching method. Hospitals should strengthen the daily management of laboratories and improve professional of the laboratory personnel. The government should strategically set up regional inspection centers to provide medical inspection services for small hospitals at the township and community levels. Manufacturers should be encouraged to develop and produce advanced instruments to continuously improve the efficiency and accuracy of the instrumental test results. Conclusions: Diversity teaching method in hight medical schools, daily management improvement of laboratories and government supporting will cultivate excellent medical laboratory personnel, improve clinical laboratory techniques.
Objective: Our study aimed to observe the dynamic epidemiological characteristics of high-risk human papillomavirus (HR-HPV) infection among women in Beijing, China, between 2015 and 2020. Methods: A retrospective analysis was performed on all collected cervical specimens from women who underwent HR-HPV examination in the outpatient clinic, ward, and physical examination center of Beijing Chao yang Hospital, Capital Medical University, from April to December 2015, and from April to December 2020. Real-time polymerase chain reaction (PCR) was applied to detect 15 HR-HPV genotypes. Results: A total of 26003 patients were enrolled in the study. No statistical difference was detected in the HR-HPV infection rate between the two years (22.1% versus 23.1%, P>0.05). The top five genotypes were HPV52/58, 16, 56 and 51, in descending order in both years. Single HR-HPV infection was the most frequent infection type in both years. The proportion of single infection in 2015 and 2020 were 73.32% (2218/3025) and 76.22% (2167/2843), respectively. There was no significant difference in infection rates across age groups in 2015, but the infection rate curve of 2020 was “bimodal”, with two peaks in young women (≤24 years-old group) group and the 60-64 years-old (y) group, with the trough in the 45-49y group. Conclusions: There was no significant change in the overall HR-HPV infection rate of women in Beijing, and the genotype distribution of HR-HPV seldom changed except for the age-related infection rate during the last 5 years. These findings may provide baseline information for local administrations topromote targeted HPV screening and HPV vaccination.
Objective: Stereotactic body radiotherapy is suitable for most pulmonary oligometastasis, but there is little data that reported the different values of SBRT combined with systemic therapy between NP and non-NP cancers. Method: This was a retrospective study on patients with pulmonary oligometastatic HNC treated with SBRT at Zhejiang Cancer Hospital. Main Results: A total of 43 patients with 65 pulmonary metastatic lesions were included in the study.24 cases originated from NP cancer, and 19 originated from non-NP cancer. The median follow-up time was 29.7 months. The 1-year local control rate was 95.4%, and 3-year PFS and OS2 were 68.7% and 46.0% in the whole group. Subgroup analysis showed local control rates were 95.1% and 95.8% in the NP group and non-NP group (p=1.000). Median PFS times were 47.0 months and 13.3months (p=0.006), and 3-year OS2 was 87.1% and 47.9% in the two groups (p=0.011). Primary tumor location, time to metastasis, number of pulmonary lesions, BED, and systemic therapy were found to be significant predictors for PFS and (or) OS2 in univariate analysis. Systemic therapy and the number of pulmonary lesions were maintained in Cox regression analysis. No SBRT-related toxicity above grade 3 was observed. Conclusion: SBRT is an effective and tolerable therapy for patients with pulmonary oligometastasis from HNC. On the basis of systemic treatment, radical curative-intent with SBRT could be achieved in selected HNC patients.
Background: Alternative splicing is an important process associated with disease including tumors. PRPF8 is a conserved protein in splice some component U5 snRNP that plays an important role in tumor cell growth. Materials and Methods: The data in The Cancer Genome Atlas was downloaded and analyzed by R Studio. The box plots showed the expression pattern of PRPF8. The chi-square test was used to manifest the association between PRPF8 expression and clinical parameters. The diagnostic value was assessed using ROC curve. The Kaplan-Meier curves and the Cox regression analysis elucidated the difference of overall survival and relapse-free survival between high expression and low expression and the prognostic value. Results: We downloaded the PRPF8 expression and the clinical data of 50 healthy individuals and 537 patients from TCGA database. We found PRPF8 expression is lower in tumor tissues than that in normal tissues and is related to age, histologic grade, pathologic stage, M classification, T classification and vital status. The Kaplan Meier curves showed the patients with lower PRPF8 expression has a poorer overall survival and relapse-free survival. The Univariate and Multivariate analysis suggested PRPF8 expression was an independent prognostic factor for overall survival and relapse-free survival in kidney renal clear cell carcinoma. Conclusion: Low PRPF8 expression is an independent predictor for overall survival and relapse-free survival in kidney renal clear cell carcinoma.
Immunomodulators play an important role in combination chemotherapy of multiple myeloma. Besides, it has been reported that leukotriene-D4 receptors play an important role in carcinogenesis. The current study was carried out to assess the possible antitumor effects of montelukast (both an immunomodulator and a CysLT1R antagonist) both in single and in combination with carfilzomib in multiple myeloma cells and the potential mechanisms. We performed our experiment using cell apoptosis assay, cell cycle assay, western blot analysis, mitochondrial transmembrane potential, and chemical proteomics based on protein activity. The results showed that montelukast inhibits cell proliferation and leads to cell apoptosis in multiple myeloma cell lines. Then we performed combination of montelukast and carfilzomib on multiple myeloma cells to explore whether they are synergistic. We demonstrated that the combination treatment leads to stronger effect of cell apoptosis. Furthermore, we demonstrated the combination effect is performed independent of the leukotriene-D4 receptors inhibition. Given that protesome inhibitor leads to accumulation of ubiquitin by inhibiting the degradation of these proteins, we tested ubiquitin levels of different groups. We found that montelukast induces ubiquitin accumulation by inhibiting Ubiquitin-Specific Protease UCHL1. All of these lead to the activity of indoplasmic reticulum stress and therefore result in cell apoptosis. This brings us a new idea in the treatment of multiple myeloma. Since montelukast is cheap and widely used in clinic, if it is proved to be effective in the treatment of multiple myeloma, it will greatly reduce the economic pressure of patients and bring new hope to patients.
Renal cell carcinoma is a common malignant urinary tumor and CXCR4 plays an important role in the development of renal cell carcinoma. However, the role of c-Src gene in the development of renal cell carcinoma is still unclear. In this study, we found that CXCR4 can directly bind to SRC and CXCR4 is involved in the regulation of c-Src expression. C-Src is highly expressed in renal cell carcinoma and promotes cell division, proliferation, invasion and reduces apoptosis in renal cell carcinoma. Highly expressed c-Src is associated with poor prognosis in patients with RCC, and affects the infiltration of CD4+ T cells and macrophages in the tumor microenvironment. In addition, high SRC expression is associated with the expression of multiple immune checkpoints, high tumor mutation burden and high microsatellite instability which indicates the potential of SRC to predict the response to the immune checkpoint block therapy.
Cancer therapy has been at the centre stage for decades in the scientific fraternity. Several chemical and biochemical actives have been studied for their effect on cancer therapy. In the present study, we have studied the therapeutic effects of a herbal formulation, Immusante, containing bioactive compounds such as Apigenin, Quercetin, Betulinic Acid, and Oleanolic Acid on cancer cell proliferation, angiogenesis and survival. The immunomodulatory effects of Immusante were incorporated in a cancer-specific mathematical model to quantify the therapeutic effects. Cancer model simulation with Immusante showed a significant reduction of tumour proliferation, reduction of immunosuppressive species, and increase in the CD8 effector T cell function. The effect of the Immusante, along with a chemotherapy drug, 5-fluorouracil (5-FU), was simulated to assess the effect of combination therapy. The addition of 5-FU as a monotherapy showed a 28% increase in the population with no/ very low tumorigenesis. A combination of 5-FU and Immusante showed a 44% increase in the population with no/very low tumorigenesis. A similar trend was seen for population size with low immune suppression, where 5-FU monotherapy showed a 26% increase, Immusante showed 12%, and a combination of 5-FU and Immusante showed a 43% increase in the population with low immune suppression, indicating increased efficiency of effector species in the presence of Immusante. Similar results were obtained for other drugs such as Cyclophosphamide, Platinum-based drugs, Vincristine, Taxane, Irinotecan, and Anthracyclines combined with Immusante. It is observed that chemotherapy alone can bring clearance in the tumour, further augmented by incorporating Immusante as a herbal adjuvant. Simulations suggest that combination enhances effectiveness and reduces the side effects of chemotherapy. It was observed that Immusante could effectively counter side-effects and adaptive response of cancer cells to improve efficacy and normalize immune response. The immunomodulatory properties of Immusante have been shown to restore balance in immune response and reduce the cytotoxic effects of drugs on healthy organs. These characteristics make Immusante a promising adjuvant during cancer management and improve the quality of the treatment.
Patients with Cancer (C) have an important risk of developing Post Traumatic Stress Disorder (PTSD), but few studies have assessed the efficiency of psychological interventions to treat it. Also, it is known that the presence of unprocessed traumatic experiences prior to diagnosis, represents a risk of the onset of a PTSD. Furthermore, no studies have analyzed the quality of such traumatic experiences during C patients life. The study has the threefold objective of assessing the effectiveness of Eye Movement Desensitization and Reprocessing therapy (EMDR) in C patients diagnosed with PTSD, examining the presence of unprocessed traumatic experiences in the pre-diagnosis lives of C patients and analyzing these clinical experience in relation to the localization of the primary cancer. Patients with C diagnosis at any stage of the disease were included, receiving either EMDR. Patients were assessed before and after (follow-up) treatments with clinical questionnaires. Patients at the first diagnosis undergo 10 sessions of psychotherapy, while patients with recurrence are subjected to 16 sessions. We had 3 patients, 2 at second stage of disease (just before to start therapy) and 1 at his third recurrence. Localization of primary cancer: Shoulder, breast, skin. Results show complete remission of PTSD in all patients, the presence of unprocessed traumatic experiences in the pre-diagnosis lives (mourning). Confirming the efficiency of EMDR in PTSD in C patients, would mean being able to rely on a powerful psychological tool in an area where the emotional aspect plays a key role in recovery patients’ psychophysical and quality of life. It is also impressive to assess the relationship between the presence of raw traumatic events prior to the communication of the diagnosis and onset of PTSD, as well as the nature of these experiences. These clinical data are essential both to plan increasingly detailed and specific treatments in terms of quality and time, and to think of a psychological prevention perspective dedicated to the person understood as a totality.
Stem cells are undifferentiated, immature, and unspecialized cells having huge potential for differentiation and proliferation into the specialized functionalized cells. More recently, CSC has been described in breast cancer and brain tumors where they make up as few as 1% of the cells in a tumor. The features of cancer stem cells are just like normal stem cells but their replication rate many times faster than normal cells. Regenerative medicines are based on stem cells, are potentially useful to regenerate damaged cells, tissues, organs and replace cancer cells with normal cells. Induced pluripotent stem cells are the most important candidates for regenerative medicines, tissue engineering, cell reprogramming, and 3D printing. Cancer Stem Cells (CSCs) have a tumorinitiating capacity and play crucial roles in tumor metastasis, relapse and chemo/ radioresistance. Because CSCs are resistant to chemotherapeutic drugs and cause recurrence of cancer and also have the ability to be regenerated; they can cause serious problems in the treatment of various cancers. Numerous biocompatible biomaterials, miRNAs, nanomaterial, artificial intelligence, and machine learning are uses to reprograms stem cells into regenerative medicines for the treatment of cancer. The present paper describes the applications and importance of stem cells in regenerative medicines, cancer stem cells targeting therapies, and the role of miRNAs in cancer stem cells targeting.
Cancer immunotherapy has emerged as a promising treatment that utilizes the innate or adaptive immunity to generate a robust killing of malignant cells. However, only a limited number of cancer patients showed responsiveness to immunotherapies such as checkpoint inhibitors, suggesting the need for potent alternative strategies. In the present study, we explored the therapeutic potentials of costimulatory molecules including TNF superfamily member 4 (TNFSF4), member 9 (TNFSF9), and member 18 (TNFSF18). In tumor samples from human colorectal and lung cancer patients, expression of these factors positively correlated with lymphocyte infiltration and expression of several immune effector genes. In syngeneic mouse tumor models, overexpression of the TNF superfamily costimulatory factors in murine colorectal or lung cancer cells significantly suppressed tumor progression. Especially, TNFSF9 and 18 showed stronger antitumor effects than TNFSF4. Together, our study demonstrated the great potential of cancer immunotherapy targeting these immune costimulatory molecules.
Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
Purpose: The MYBL1 gene is a strong transcriptional activator, associated with cell cycle signaling and differentiation. Data show the gene is overexpressed in triple negative breast cancers. Considering the possibility that MYBL1 might be involved in events associated with the pathogenesis of these cancers, we sought to identify genes associated with MYBL1 expression in triple negative breast cancer. Methods: shRNA lentiviral knockdown was used to down-regulate the MYBL1 gene. Microarray analyses were used to identify genes either directly or indirectly affected by targeting MYBL1 knockdown. Data analyses was performed utilizing Affymetrix TAC 4.0, Chip X transcription factor analyses, Target Scan miRNA analyses, and STRING analyses was used to determine protein: protein interaction and pathway analyses. Web Gestalt and Gene Ontology were used to determine pathway and gene-set enrichments. Publicly available patient and cell line datasets were retrieved and processed using resources available in Gene Expression Omnibus and Oncomine. The polymerase chain reaction and western analyses were used to determine transcript and protein levels, respectively. Results: Knockdown of MYBL1 in a triple negative breast cell line led to down-regulation of MYBL2, TCF19, KIF18b along with an enrichment of cell cycle signaling genes. Gene expression analyses show that MYBL1, MYBL2, TCF19 and KIF18b display a similar pattern of expression in breast cell lines and many of the archival patient datasets examined. Conclusion: TNBC is a heterogeneous subtype, so these data suggest that cancers that over-express MYBL1, express MYBL2, TCF19 and KIF18b. Bioinformatic analyses suggest MYBL1 regulates MYBL2 which leads to regulation of TCF19 and KIF18b.
GSK-3β is a key regulator in insulin, Wnt and NF-κB signaling pathways. Dysregulation of GSK-3β is often related to tumors and diabetes. Inhibiting it might provide cure for diabetes, tumors, neurodegeneration and brain ischemia. Although there are a number of reported GSK-3β inhibitors, the scaffold is limited. Herein we report a discriminatory analysis-based molecular docking on the Specs database, and identified 3 novel GSK-3β inhibitors with moderate IC50 (ranging from 17.42 μM to 6.74 μM) in the following in vitro biological test. Further dynamic simulations and docking pose analysis were performed to give a better understanding on the binding conformation of 3 hit compounds AK- 777/09836064, AK-968/37185006 and AN-698/41607072, which would provide basis for further optimization.
Anti-Hu syndrome is a rare autoantibody associated paraneoplastic disease of the central and peripheral nervous system resulting in a variety of neurological symptoms. In pediatric patients it is described in the context of (ganglio) neuroblastoma associated Opsoclonus-Myoclonus Syndrome (OMS) and other paraneoplastic syndromes. The timely diagnosis of paraneoplastic autoimmunity in childhood is hampered by its rarity as well as by the diversity of clinical symptoms that may occur. We report a 4-year-old boy with gastrointestinal disorder and neurological symptoms due to neuroblastomaassociated anti-Hu syndrome. The patient stabilized under a multimodal oncologic, immunosuppressive and antiepileptic treatment regimen. Treatment of neuroblastoma was individually modified and especially the specific anti- GD2 post-consolidation therapy was substituted by oral cyclophosphamide maintenance therapy in order not to aggravate autoimmune encephalitis. At the age of 8 years, the boy has been in ongoing complete oncologic remission for two years after end of relapse treatment. However, he suffers from neurologic symptoms like focal epilepsy and late sequelae of the oncologic disease. This case shows that treatment of paraneoplastic anti-Hu syndrome is challenging, encephalitis may persist long after oncologic remission and may lead to developmental delay and a variety of physical sequelae.
Regular Physical Activity (PA) improves the outcomes of patients with cancer mainly by enhancing the immune system. The relationship of PA and the derived Neutrophil-to-Lymphocyte Ratio (dNLR) with the evolution of 31 consecutive patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck (R/M SCCHN) treated with immunotherapy was determined in this retrospective study. Seventeen patients (55%) performed PA and 14 (45%) did not. The time to progression and Overall Survival (OS) was significantly better in the first compared to the second group (p=0.002 and 0.0019, respectively). In patients with a dNLR less than 3.5 the survival was significantly longer than in patients with a higher dNLR (p=0.004). Our results suggest that there is an association between PA and improved outcomes in R/M SCCHN patients treated with immunotherapy and that the dNLR is a predictive marker of good response to treatment.
Proline metabolism plays an essential role in tumor development; however, its underlying mechanism in CRC remains elusive. B7-H3, an immune checkpoint member of the B7 immunoregulatory family, is aberrantly overexpressed in a wide variety of malignancies and is associated with a poor prognosis. In this study, we found that overexpression of B7-H3 effectively enhanced proline consumption rate and reduced glutamate production, while knockout of B7-H3 had inverse effects. Moreover, we also identified that B7-H3 increased proline consumption and decreased glutamate production by promoting the expression of Pyrroline- 5-carboxylate reductase 1 (PYCR1) in CRC cells and that PYCR1 is a crucial mediator of B7-H3-induced CRC proliferation and migration. Overexpression of PYCR1 or treatment of cells with PYCR1 inhibitors could reverse B7-H3-induced proline metabolism and B7-H3-induced tumor cell proliferation and migration. Furthermore, we confirmed the positive correlation between B7-H3 and PYCR1 expression in tumor tissues of CRC patients. Collectively, the present study highlighted a previously unrecognized mechanism of B7-H3-mediated rewiring of proline metabolism through increased expression of PYCR1 in CRC cells. These findings suggested that B7-H3 may serve as a novel prognostic factor and a promising therapeutic target for CRC.
Terminal sugar-alteration in carbohydrate chains such as GalNAc replacing Gal in prostate and pancreatic cancers and Gal3-O-sulfation in breast, colon and gastric tumors could play a crucial role in cancer pathogenesis. We found the activities of cancer cell GalNAc transferases (GalNAc-Ts) as 0%, 0% <20%, 20-50% and 20-120% respectively towards Galβ1-3GalNAcα-OBn, 4-FGlcNAcβ1-6 (Galβ1-3)GalNAcα-O-Bn, LacNAcβ-O-Bn, GlcNAcβ1-4 GlcNAcβ-O-Bn and GlcNAcβ1-6GalNAcα-O-Bn as compared to GlcNAcβ-OBn. α-[6-³H]GalNAc-ylated endogenous cancer cells Ser/Thr polypeptides by the corresponding cancer cell αGalNAc-T were at variable levels, heterogenous, and exhibited complete binding to VVL-agarose and non-binding to WGA-, WFL- and ConA- agarose. PNA-agarose binding and non-binding radioactive products from [6-³H] GalNAc-ylated exogenous acceptor GlcNAcβ1-6(Galβ1-3) GalNAcα-O-Al indicated cancer type variable β1-3Galactosidase activities at neutral pH. TLC analysis identified two radioactive products by confirming PNA-agarose data. WGA-agarose tight binding and VVL-agarose weak binding respectively of the products [6-³H] GalNAcβ1-4 and β1-3GlcNAcβ-OBn isolated from the exogenous acceptor GlcNAc-β-O-Bn by Sep-Pak C18 method were used to quantitate β1-4 and β1- 3GalNAc-T activities in cancer cells. DU4475, MDA-MB-435S, PA-1, LNCaP, PC3, DU145, EG7 and GL261- OVA over-expressed β1-3GalNAc-T activity. Tumorigenic MDA-MB-435/LLC6 as compared to non-tumorigenic MDA-MB-435S contained ~2-fold each of αGalNAc-T and β1-4GalNAc-T. The breast cancer DU4475 uniquely expressed 10-fold β1-3GalNAc-T with respect to β1-4GalNAc-T. HPLC identified negligible β1-6GalNAc-T in cancer cells and high-level β1-3GalNAc-T in pancreatic and gastric tumors. It is known that Tn epitopes correlate with cancer progression and metastasis and β-galactosidase is a senescence-biomarker and moleculartarget for ovarian cancer. It is apparent that βGalNAc-T, Tn polypeptides, αGalNAc-T and neutral β1-3galactosidase could play a crucial role in cancer pathogenesis.
Objective: Bone suppression of chest radiograph holds great promise to improve the localization accuracy in Image-Guided Radiation Therapy (IGRT). However, data scarcity has long been considered as the prime culprit of developing Convolutional Neural Networks (CNNs) models for the task of bone suppression. In this study, we explored the effectiveness of various data augmentation techniques for the task of bone suppression. Methods: In this study, chest radiograph and bone-free chest radiograph are derived from 59 high-resolution CT scans. Two CNN models (U-Net and Generative Adversarial Network (GAN)) were adapted to explore the effectiveness of various data augmentation techniques for bone signal suppression in the chest radiograph. Lung radiograph and bone-free radiograph were used as the input and target label, respectively. Impacts of six typical data augmentation techniques (flip, cropping, noise injection, rotation, shift and zoom) on model performance were investigated. A series of statistical evaluating metrics, including Peak Signal-To-Noise Ratio (PSNR), Structural Similarity (SSIM) and Mean Absolute Error (MAR), were deployed to comprehensively assess the prediction performance of the two networks under the six data augmentation strategies. Quantitative comparative results showed that different data augmentation techniques exhibited a varying degree of influence on the performance of CNN models in the task of CR bone signal suppression. Results: For the U-Net model, flips, rotation (10 to 20 degrees), all the shifts, and zoom (1/8) resulted in improved model prediction accuracy. By contrast, other studied augmentation techniques showed adverse impacts on the model performance. For the GAN model, it was found to be more sensitive to the studied augmentation techniques than the U-Net. Vertical flip was the only augmentation method that yielded enhanced model performance. Conclusion: In this study, we found that different data augmentation techniques resulted in a varying degree of impacts on the prediction performance of U-Net and GAN models in the task of bone suppression in CR. However, it remains challenging to determine the optimal parameter settings for each augmentation technique. In the future, a more comprehensive evaluation is still warranted to evaluate the effectiveness of different augmentation techniques in task-specific image synthesis.
