Survival Of Certain Types Research Articles

The preoperative systemic inflammation response index (SIRI) independently predicts survival in postmenopausal women with breast cancer

The recently developed preoperative systemic inflammation response index (SIRI) was reported as a useful biomarker that could predict survival in certain types of malignant tumors. However, the prognostic value of preoperative SIRI in postmenopausal breast cancer remains unclear. This study aimed to explore the relationship between SIRI and survival in postmenopausal patients with breast cancer. A total of 390 postmenopausal patients with breast cancer who underwent a mastectomy at Sun Yat-sen University Cancer Center were retrospectively studied. SIRI was based on peripheral neutrophil, monocyte, and lymphocyte counts, calculated as: neutrophil count × monocyte count/lymphocyte count. The best cut-off value for SIRI was determined using receiver operating characteristic curve analysis. Patients were divided into 2 groups:Low SIRI < 0.54 and high SIRI > 0.54. High SIRI was significantly related to progesterone receptor status. Kaplan-Meier survival analysis showed that T stage, N stage, clinical stage, carcinoembryonic antigen, estrogen receptor, progesterone receptor, endocrinotherapy, and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI could also independently predict OS. Preoperative SIRI may be a reliable predictor of OS in postmenopausal patients with operable breast cancer to provide personalized prognostication and to assist in the formulation of a clinical treatment strategy.

Distant reading as a strategy of an exact study of bibliography

In recent times marked by the offensive and largescale advancement of computer technol-ogy numerous libraries, scientific and educational centers in the world are creating their own extensive databases of literary and bibliographic texts. Facing such databases the close reading method designed to work with specific texts would seem to lose its meaning. The Italian sociolo-gist and literary critic Franco Moretti became the main critic of the close reading. He presented his ideas in the book «Distant Reading». This book can be viewed as a program to update the methodology of studying world literature. Moretti believes that the world literature should be studied not by looking at the details, but by examining it from a long distance: studying hudreds and thousands of texts. He suggest to use the Digital Humanities (DH) methods, i.e. to ap-ply digital (computer) methods in the humanities. To show the reasons for the survival of certain types of texts, Moretti compares literary processes with biological ones and draws an anology between natural selection and reader selection. Moretti’s predecessor, who first used quantitative methods in literary studies and saw common ground between literary and biological processes, was the author of the fundamental monograph “Methodology of an exact study of literature” B. I. Yarkho (18891942).Moretti’s book “Distant Reading” shatters stereotypes of the bibliographic environment. It is directed no to the study of close (slow) reading, but to the study of the entire world docmentary flow. This approach opens the way to the use of quantitative methods in the study of world bibliography. A new research strategy “exact study of bibliography” will be formed as part of digital and automated text processing.

Fyn is recruited to specialized clathrin coated pits and regulates EGF receptor signaling

The Epidermal Growth Factor (EGF) Receptor (EGFR) is a key receptor tyrosine kinase that controls many facets of cell physiology, including proliferation, survival and migration. EGF stimulation elicits EGFR phosphorylation and/or membrane recruitment of Grb2, Gab1 and phosphatidylinositol‐3‐kinase (PI3K), resulting in production of phosphatidylinositol‐3,4,5‐trisphosphate (PIP3), leading to Akt activation. Concomitantly upon ligand binding, EGFR is simultaneously recruited to clathrin‐coated pits (CCPs), eventually leading to receptor endocytosis. We previously uncovered that perturbation of clathrin, but not of receptor endocytosis, impairs EGF‐stimulated activation of Akt signaling (Garay et al. 2015. Mol Biol Cell.26:3504–19). Moreover, we found that some key EGFR signaling intermediates such as phosphorylated Gab1 are enriched with some CCPs. We thus proposed that in addition to their function as endocytic portals, some CCPs have a direct role in controlling EGFR signaling. How CCPs and clathrin directly control the spatiotemporal properties of EGFR signaling at the plasma membrane prior to receptor endocytosis had remained poorly understood. We uncovered that perturbations of TOM1L1 (a clathrin‐binding regulator of Src‐family kinases) and the TOM1L1‐binding Src‐family kinase Fyn impaired EGF‐stimulated Akt phosphorylation, similarly to the effects of clathrin perturbations. We found that TOM1L1 and Fyn are enriched within a subset of CCPs that also contain EGFR, and that perturbation of TOM1L1 prevented Fyn recruitment to CCPs. Importantly, TOM1L1‐ or Fyn‐positive CCPs exhibit unique properties, such as distinct lifetimes, compared to other CCPs. Thus, our results indicate that a subset of CCPs is specialized by enrichment with key signaling regulators to control EGFR signaling, a phenomenon required for subsequent Akt activation. Given the importance of EGFR in driving growth and survival of certain types of cancer, obtaining a better understanding of how CCPs organize key EGFR signals in space and time within the PM may lead to the development of novel anti‐cancer treatments.Support or Funding InformationFunding for this research was provided by an Operating Grant (no. 125854), a Project Grant and a New Investigator Salary Award from the Canadian Institutes of Health Research, as well as an Early Researcher Award (Ontario Ministry of Research, Innovation and Science) to C.N.A., and an Ontario Graduate Scholarship to S.L.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Single institution experience on cancer among adolescents 15-19 years of age.

Yağcı-Küpeli B, Akyüz C, Yalçın B, Varan A, Kutluk T, Büyükpamukçu M. Single institution experience on cancer among adolescents 15-19 years of age. Turk J Pediatr 2017; 59: 1-5. Adolescent cancers differ from other age groups in terms of cancer types, treatment and outcome. We aimed to present our institutional data on survival of certain types of cancer in adolescents. Hospital files were retrospectively evaluated for distribution of tumor types, clinical features, and overall and event-free survival (OS and EFS) rates in adolescents with malignant tumors. Two hundred ninety-three cases between 15-19 years who were diagnosed with malignant tumor at our department in the last 38 years were included in the study. Mean age was 15.3 and median age was 15 years at time of diagnosis. Male/female ratio was found to be 1.8/1. The most common cancers were non-Hodgkin lymphoma (NHL) (20.5%), Hodgkin's lymphoma (HL) (19.8%), central nervous system (CNS) tumors (10.9%), osteosarcoma (10.6%), Ewing sarcoma/primitive neuroectodermal tumors (EWN/PNET (9.9%) nasopharyngeal carcinoma (NPC) (9.6%). Non-compliance to medical treatment was observed in 10.9% of cases with significantly high non-compliance in NHL and osteosarcoma (p=0.02). Overall survival was 57.6% and EFS was 45.7% at a median follow-up time of 8.75 years. In adolescents, lower OS and EFS rates than the younger age group are observed. The most appropriate management plan should be made according to the physical and psychosocial needs of patients in this age group.

The sky is falling: evidence of a negativity bias in the social transmission of information

The method of serial reproduction has revealed that the social transmission of information is characterized by the gradual transformation of the original message. This transformation results from the preferential survival of certain types of information and the resolution of ambiguity. Here we present evidence of a bias favoring the social transmission of negatively-valenced information across multiple transmission episodes. Ninety-two, four-person chains transmitted a story containing unambiguously positive and unambiguously negative story events, along with ambiguous story events that could be interpreted positively or negatively. Analysis using mixed-effects modeling revealed the preferential survival of unambiguously negative events over positive events, and the increasingly negative resolution of ambiguous events across successive transmission episodes. Contrary to predictions, elevated state anxiety did not enhance the social transmission of negatively-valenced information. We also found that the survival of unambiguously negative story events was positively correlated with the negative resolution of ambiguous story events, reflecting a general negativity-bias in the social transmission of information.

Concurrent radiotherapy and weekly chemotherapy of 5-fluorouracil and platinum agents for postoperative locoregional recurrence of oesophageal squamous cell carcinoma

The most optimal management for postoperative locoregional recurrence of oesophageal squamous cell carcinoma is still controversial. Several studies have reported the feasibility and efficacy of concurrent chemoradiotherapy (CCRT), mostly with three-weekly or four-weekly schedule of chemotherapy. However, treatment compliance was not quite satisfactory, probably due to treatment-related toxicities. Since CCRT with weekly chemotherapy regimens have demonstrated a favorable toxicity profile as well as promising survival in certain types of cancer, we aimed to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly chemotherapy with 5-fluorouracil (5-FU) and platinum agents for patients with postoperative locoregional recurrence of oesophageal squamous cell carcinoma in our center. Twenty-seven consecutive patients who were diagnosed with postoperative locoregional recurrence of oesophageal squamous cell carcinoma and received CCRT with weekly chemotherapy of 5-FU and platinum agents were retrospectively analyzed. Our data showed that the present protocol of radiotherapy combined concurrently with weekly chemotherapy of 5-FU and platinum agents was a safe and effective salvage treatment for postoperative locoregional recurrence of oesophageal squamous cell carcinoma.

Evaluating the Role of EUS-FNA in the Diagnosis of Metastasis to the Pancreas: Results From a Tertiary Cancer Center

Introduction: Metastasis to the pancreas is less than 5% of all tumors detected in the pancreas. Accurate diagnosis of isolated metastasis to the pancreas can lead to metastatectomy with improvement in survival in certain types of primary cancers. Furthermore, in patients with more than 1 malignancy, identifying the source of the metastasis is important for further management. To evaluate the role of EUS-FNA in the diagnosis of metastasis to the pancreas. Methods: The study was approved by the institutional review board. Retrospective chart review was conducted to identify all patients suspected to have a metastatic lesion to the pancreas on imaging (CT, MRI, PET) and confirmed on FNA (EUS-FNA or IR-guided biopsy) between 2002 and 2014. Results: A total of 70 patients (median age: 64 years [range: 35-83]; males: 43 [61%]) were found to have metastatic pancreatic lesions. EUS-FNA was performed in 54 patients and detected the pancreatic lesions in all patients with one mild pancreatitis. Among the 54 patients who had an EUS-FNA, 22 patients had multiple lesions, 32 patients had single lesions (head [15], body [9], tail [8]). A 22 G needle was used in 17 patients, and 25 G needle was used in 29 patients, and both needles used in 1 patient (missing information on needle size in 7 patients). A median of 3 passes (range:1-7) were done. Rapid onsite evaluation was performed on all patients for specimen adequacy. Specimens obtained via EUS-FNA were diagnostic in 53/54 patients. Specimens obtained via IR-guided biopsy were diagnostic in 17/19 patients. EUS-FNA was diagnostic in 2 patients who had previously undergone a non-diagnostic IR-guided biopsy. IRguided biopsy was diagnostic in 2 patients who had previously undergone a non-diagnostic EUS-FNA. Thus the accuracy was 98% for EUS-FNA and 89% for IR-guided biopsy. Immunoperoxidase stains were performed and contributory to the diagnosis on 35 patients (26 with a cellblock and 9 with cell smears). Cytomorphologic comparison with the primary tumor was used to make a diagnosis on the other 35 patients (13 with a cellblock and 22 with cell smears). There were 7 patients with more than 1 primary cancer, with diagnosis provided by immunostaining in 6 patients (5 with cellblock and 1 with cellsmear) and cytomorphologic comparison with primary tumors in 1 patient. Conclusion: EUS-FNA has a high diagnostic yield and low complication rate in patients with metastasis to the pancreas. Immunocytochemistry and comparison of the cytomorphology with the primary cancer when possible enable accurate diagnosis especially in patients with more than one primary cancer.

The association between pre-treatment serum 25-hydroxyvitamin D and survival in stage IV prostate cancer.

5036 Background: Emerging evidence in the literature suggests a positive association between serum 25-hydroxyvitamin D [25(OH)D], a standard indicator of vitamin D status, and survival in certain types of cancer. We investigated this relationship in newly diagnosed stage IV prostate cancer patients. Methods: A case series of 54 newly diagnosed stage IV prostate cancer patients underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between Jan 2008 and Dec 2010. We defined vitamin D insufficiency as serum 25(OH)D levels of &lt;=32 ng/ml. Patient survival was defined as the time between date of first patient visit and date of death from any cause/date of last contact. Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for age, prostate specific antigen (PSA) and functional status. Results: Mean age at diagnosis was 59.6 years. During a median follow-up of 23.6 months, 16 deaths occurred. The mean serum 25(OH)D was 30.1 ng/ml, among whom 38 (70.4%) were insufficient in vitamin D (&lt;=32 ng/ml). Mean overall survival was 49.4 months (95% CI: 38.1-60.7). Mean survival was 32.6 months and 62.4 months for patients in &lt;=32 ng/ml and &gt;32 ng/ml groups respectively (p = 0.02). On univariate analysis, patients with levels &gt;32 ng/ml had a significantly lower risk of mortality compared to those with levels &lt;=32 ng/ml (HR=0.19; 95% CI: 0.04-0.87; p=0.03). On multivariate analysis controlling for age, performance status and PSA, patients with levels &gt;32 ng/ml demonstrated significantly lower mortality (HR=0.13; 95% CI: 0.02-1.0; p=0.05) compared to those with levels &lt;=32 ng/ml. Conclusions: Higher circulating levels of serum 25(OH)D were positively associated with survival in patients with metastatic prostate cancer. While these results need to be confirmed in prospective clinical trials, our study adds to the growing body of literature on the prognostic role of serum vitamin D in cancer. Given the high prevalence of vitamin D insufficiency in prostate cancer and the fact that this insufficiency is easily correctable by supplementation, we recommend early vitamin D assessment and intervention for a potential impact on patient survival.

RNA-Binding Protein Musashi1 Modulates Glioma Cell Growth through the Post-Transcriptional Regulation of Notch and PI3 Kinase/Akt Signaling Pathways

Musashi1 (MSI1) is an RNA-binding protein that plays critical roles in nervous-system development and stem-cell self-renewal. Here, we examined its role in the progression of glioma. Short hairpin RNA (shRNA)-based MSI1-knock down (KD) in glioblastoma and medulloblastoma cells resulted in a significantly lower number of self renewing colony on day 30 (a 65% reduction), compared with non-silencing shRNA-treated control cells, indicative of an inhibitory effect of MSI1-KD on tumor cell growth and survival. Immunocytochemical staining of the MSI1-KD glioblastoma cells indicated that they ectopically expressed metaphase markers. In addition, a 2.2-fold increase in the number of MSI1-KD cells in the G2/M phase was observed. Thus, MSI1-KD caused the prolongation of mitosis and reduced the cell survival, although the expression of activated Caspase-3 was unaltered. We further showed that MSI1-KD glioblastoma cells xenografted into the brains of NOD/SCID mice formed tumors that were 96.6% smaller, as measured by a bioluminescence imaging system (BLI), than non-KD cells, and the host survival was longer (49.3±6.1 days vs. 33.6±3.6 days; P<0.01). These findings and other cell biological analyses suggested that the reduction of MSI1 in glioma cells prolonged the cell cycle by inducing the accumulation of Cyclin B1. Furthermore, MSI1-KD reduced the activities of the Notch and PI3 kinase-Akt signaling pathways, through the up-regulation of Numb and PTEN, respectively. Exposure of glioma cells to chemical inhibitors of these pathways reduced the number of spheres and living cells, as did MSI1-KD. These results suggest that MSI1 increases the growth and/or survival of certain types of glioma cells by promoting the activation of both Notch and PI3 kinase/Akt signaling.

Autocrine TGF-β protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim

Cancer cells undergo multi-step processes in obtaining the ability to metastasize, and are constantly exposed to signals that induce apoptosis. Acquisition of anti-apoptotic properties by cancer cells is important for metastasis, and recent studies suggest that transforming growth factor (TGF)-β promotes the survival of certain types of cancer cells. Here, we found that in highly metastatic breast cancer cells, JygMC(A), JygMC(B) and 4T1, TGF-β ligands were produced in autocrine fashion. Pharmacological inhibition of endogenous TGF-β signalling by a TGF-β type I receptor kinase inhibitor in serum-free conditions increased the expression of BH3-only protein, Bim (also known as Bcl2-like 11) in JygMC(A) and JygMC(B) cells, and caused apoptotic cell death. We also found that induction of Bim by TGF-β was not observed in Foxc1 knocked-down cancer cells. These findings suggest that TGF-β plays a crucial role in the regulation of survival of certain types of cancer cells through the TGF-β-Foxc1-Bim pathway, and that specific inhibitors of TGF-β signalling might be useful as apoptosis inducers in breast cancer cells.

Apes, lice and prehistory

Although most epidemic human infectious diseases are caused by recently introduced pathogens, cospeciation of parasite and host is commonplace for endemic infections. Occasional host infidelity, however, provides the endemic parasite with an opportunity to survive the potential extinction of its host. Such infidelity may account for the survival of certain types of human lice, and it is currently exemplified by viruses such as HIV.

Autocrine motility factor receptor expression in patients with stage I non–small cell lung cancer

Background. Expression of autocrine motility factor receptor (AMFR) associates with increased cell migration and poor survival in certain types of human cancers. We assessed the possible correlation between AMFR, clinicopathologic features, and survival in stage I non–small cell lung cancer (NSCLC). Methods. AMFR expression was analyzed immunohistochemically, using a monoclonal antibody (3F3A) in tumor specimens from 97 patients with curative resection. Vascular endothelial growth factor (VEGF) expression was also examined after accounting for AMFR expression. Results. Out of 97 tumors, 38 (39.2%) were positively stained with AMFR. The AMFR expression was significantly associated with histologic type of tumor, mainly in adenocarcinoma. Overall survival of patients with AMFR-positive tumors was significantly worse than that of AMFR-negative tumors ( p = 0.0050). The AMFR expression appears to be associated with VEGF expression. Patients who were AMFR positive and had high VEGF expression had a worse prognosis compared with the AMFR-negative and low VEGF-expression group ( p < 0.0001). Multivariate analysis revealed an independent prognostic impact of AMFR on survival ( p = 0.0039). Conclusions. These results indicate that evaluation of AMFR expression may provide useful guidance in follow-up of patients with NSCLC.

Biological significance of the expression of urokinase-type plasminogen activator receptors (uPARs) in brain tumors.

The urokinase-type plasminogen activator receptor (uPAR) plays a critical role in the regulation of cell-surface plasminogen activation in several physiological and pathological conditions. Recent evidence suggests that the uPAR is also involved in processes that are not related to plasminogen activation, including cell adhesion and transmission of extracellular signals across the plasma membrane. The uPAR influences cell migration and spreading both in vivo and in vitro through the cell-surface activation of plasminogen. The uPAR can bind to vitronectin, an adhesive extracellular matrix protein that contains the Arg-gly-Asp (RGD) cell adhesion domain and that serves as a ligand for several integrin receptors. uPAR also forms complexes with (1, (2, and (3 integrins, thereby allowing mutual interactions and regulation between cell adhesion and proteolysis. Recently, uPAR has been shown to have strong prognostic value for predicting disease recurrence and overall survival in certain types of cancer. We discuss here the biological significance of uPAR in the glioblastoma invasion process. Strong correlations found between elevated uPAR levels in glioblastoma cells and tumor invasiveness have led to uPAR being selected as a target for therapy in experimental animal models. Using antisense vectors to down regulate uPAR expression at the level of the mRNA and protein in glioblastoma cells, has been shown to inhibit tumor formation in nude mice. These results provide a potential basis from which to develop novel therapeutic strategies to direct the expression of antisense uPAR and to evaluate the efficiency of this technique for cancer gene therapy in patients with brain tumor.

The effect of microcolony size, at time of irradiation, on colony forming ability

Purpose: To investigate the effect of irradiating microcolonies of various sizes on their subsequent ability to form colonies. Materials and methods: The location of individual HPV-G cells in tissue culture flasks was recorded using computerized microscopy. This allowed the cells' positions to be continually revisited, which enabled manual sizing of individual microcolonies both at the time of irradiation (between 0-5Gy) and following an incubation period during which the microcolonies were assessed for cologenic survival. Results: The experiments indicate that when irradiated as microcolonies, cells have plating e ciencies (PE) that are lower than expected when compared with the prediction from the PE values of cells irradiated individually. Conclusion: These data support the conclusions of Mothersill and Seymour (1997b) which challenge the concept of independent survival of certain types of cells following irradiation. The results indicate that interactions between cells can occur even in small aggregates.

Neutrophil apoptosis is delayed by the diadenosine polyphosphates, Ap5A and Ap6A: synergism with granulocyte-macrophage colony-stimulating factor.

In addition to ATP, platelets and other cell types can secrete high quantities of diadenosine polyphosphates Ap3A, Ap4A, Ap5A and Ap6A. There is increasing evidence to show that these molecules can function as novel modulators of cell function. For this report we have measured the effects of the diadenosine polyphosphates Ap5A and Ap6A on neutrophil apoptosis. These molecules can themselves delay neutrophil apoptosis (as assessed by morphology, function. CD16 expression and chromatin integrity), and are as effective on a molar basis as ATP, Ap3A and Ap4A. Moreover, these dinucleotides act synergistically with granulocyte-macrophage colony-stimulating factor (GM-CSF) to delay neutrophil apoptosis. Thus, diadenosine polyphosphates may act, in concert with cytokines, as novel modulators of neutrophil function and survival in certain types of inflammatory conditions.

Synaptic transmission between rat superior cervical ganglion neurons in dissociated cell cultures

The principal neurons of the rat superior cervical ganglion (SCGN) when established as dissociated cells in tissue culture form synapses among themselves. In the present study we have examined this synaptic interaction when these neurons are co-cultured with several other types of tissues. Dissociated SCGN were prepared from perinatal rats and studied, after 3–4 weeks maturation, with intracellular recording techniques. Synaptic interactions between sympathetic neurons were demonstrated when these cells were: (a) grown with explants from newborn rat thoratic spinal cord, (b) when the SCGN had survived for several weeks subsequent to removal of hte spinal cord explants, and (c) when the SCGN were grown in the presence of an adrenergic target (interscapular brown fat cells). Unidirectional, reciprocal, recurrent and complex chemical synaptic networks, consisting of conergence and divergence, characterized connections between SCGN. All synaptic responses were cholinergic since they were reversibly blocked by hexamethonium or mecamylamine but were not sensitive to 10 −5 M phenoxybenzamine. Removal of the spinal cord explants did not significantly alter the proportion of chemical synaptic interactions between SCGN (more than 25%) from matched cultures. Anatomical observations established that in cultures with brown fat, innevating neurites appeared on the fat cells: these neurites frequently expanded to form varicosities that resembled the adrenergic terminals normally seen on brown fat in the animal. Synaptic profiles also occured on the neurons in these cultures and some of these were shown to be cholinergic. The proportion of neuronal interactions in the combined SCGN + fat cultures was low, however, suggesting that co-culture with target tissue might influence the frequency of interconnections developed between SCGN in culture. Other factors, such as the presence of non-neuronal cells, degree of dissociation, cellular density, culture age and the survival of certain types of SCGN in culture are discussed as variables related to the formation of synapses between SCGN. Non-retified electrical coupling between SCGN was also observed in 17 out of 679 pairs (2.5%) of neurons. Attenuation factor for electrically coupled action potentials ranged between 1 and 43.5.