Lower Median Survival Time Research Articles

Analysis of Risk Factors for Death from Melanoma and Genitourinary Diseases in Male Patients with Cutaneous Melanoma: A Cohort Propensity Score Matching Study.

To analyze the influencing factors of male cutaneous melanoma (CM) patients dying from genitourinary diseases (GUD). We searched the surveillance, epidemiology, and end results (SEER) database and extracted data on male CM patients according to the inclusion and exclusion criteria, including male patients whose cause of death was CM (cohort A) or GUD (cohort B). Comparisons between the two cohorts were performed before and after propensity score matching (PSM). An interaction analysis between age and year of diagnosis was also conducted. Cox regression analysis were performed to find the risk factors for death from GUD. Seven thousand seventy-eight CM patients were included, including 6415 (90.6%) in cohort A and 663 (9.4%) in cohort B. Compared with cohort A, cohort B patients were older (median age 74 ys. vs 65 ys.) and were more under the localized stage and had longer survival time no matter before or after PSM (all p<0.001). The stage was an inhibitory factor for cohort B (p <0.001). After PSM, only age and year of diagnosis were found to be cohort B's promoting factors (p<0.001). The interaction analysis showed that older patients diagnosed in later years (2009-2020) had a higher risk of dying from GUD compared to those diagnosed earlier (p<0.05). Patients with a later year of diagnosis (2009-2020) had a lower median survival time than patients with an earlier year of diagnosis (2000-2008) (p<0.001). When the patient's year of diagnosis was earlier (2000-2008), older patients (>75 ys.) had a higher risk of dying from GUD than younger patients (≤75 ys.) (p<0.001). We first reported a significant interaction between age and year of diagnosis in male CM patients dying from GUD, highlighting the increased risk in older patients diagnosed more recently. We may pay attention to the possibility of dying from genitourinary diseases for CM patients.

High-Grade Gliomas from Subventricular Zone: Proteomic Drivers of Aggressiveness Using Fluorescence-Guided Multiple Sampling.

High-grade gliomas (HGGs) are among the most aggressive brain tumors and are characterized by dismally low median survival time. Of the many factors influencing the survival of patients with HGGs, proximity to the subventricular zone (SVZ) is one of the key influencers. In this context, 5-amino levulinic acid fluorescence-guided multiple sampling (FGMS) offers the prospect of understanding patient-to-patient molecular heterogeneity driving the aggressiveness of these tumors. Using high-resolution liquid chromatography-mass spectrometry (MS)/MS proteomics for HGGs from seven patients (four SVZ associated and three SVZ nonassociated), this study aimed to uncover the mechanisms driving the aggressiveness in SVZ-associated (SVZ+) HGGs. Differential proteomics analysis revealed significant dysregulation of 11 proteins, of which 9 proteins were upregulated and 2 were downregulated in SVZ+ HGGs compared to SVZ-non-associated (SVZ-) HGGs. The gene set enrichment analysis (GSEA) of the proteomics dataset revealed enrichment of MYC targets V1 and V2, G2M checkpoints, and E2F targets in SVZ+ HGGs. With GSEA, we also compared the pathways enriched in glioma stem cell subpopulations and observed a similar expression trend for most pathways in our data. In conclusion, this study reveals new and emerging insights on pathways that may potentially contribute to greater aggressiveness in SVZ+ HGGs. Future studies using FGMS in larger cohorts are recommended to help uncover the proteomics and molecular basis of aggressiveness and stemness in HGGs.

Clinical Features of Patients With Hematological Malignancies Treated at the Palliative Care Unit.

In Japan, the number of patients with aggressive hematological malignancies (PHMs) admitted at the palliative care unit (PCU) in their end-of-life (EOL) stage was fewer than that of patients with solid tumors due to several reasons. The assessment of patient characteristics and the methods of survival prediction among PHMs in the EOL stage are warranted. This study aimed to identify the current medical status and the method of survival prediction among PHMs treated at the PCU. We retrospectively analyzed the clinical data of 25 PHMs treated at our PCU between January 2017 and December 2020. The association between survival time and the palliative prognostic score (PAP) and palliative prognostic index (PPI) was analyzed. The average age of the PHMs was higher than that of patients with lung cancer as a control. The median survival time of the PHMs was shorter than the control group. Most PHMs could not receive standard chemotherapy, and the most common cause of death was disease-related organ failure. Significant associations were observed between the survival time and each PAP/PPI value in patients with malignant lymphoma, but not in those with leukemia. The PHMs in the PCU had a lower median survival time than the control group. These results were induced by the result of patient selection to avoid treatment-related severe toxicity. The survival prediction using the PAP and PPI was less accurate in patients with leukemia.

Quantification of circulating tumour cells over time in dogs with appendicular osteosarcoma.

Enumeration of circulating tumour cells (CTC) has shown promise for prognostication and guidance of therapeutic decisions in human cancers. The objective of this study was to enumerate CTC over time in dogs with naturally occurring osteosarcoma (OSA), and to determine correlation with patient outcome. Twenty-six dogs with OSA and no evidence of metastatic disease at the time of amputation were enrolled. Dogs were assessed for lung metastases and CTC prior to and following amputation, and at each chemotherapy visit. Twenty-one dogs completed the study. Nineteen dogs were euthanized and two were alive and free of metastases. Overall survival time ranged from 88 to 1058 days (median survival time (MST) 374 days). Increased serum alkaline phosphatase activity, advanced age, and higher body weight were significantly associated with lower MST. Dogs with OSA had a mean of 356 (0 to 4443) CTC/106 leukocytes. In 12 of 15 dogs that developed radiographic evidence of metastasis, a pre-metastatic CTC spike was retrospectively detectable on average 36.5 (1-100 days) days prior to metastasis and was associated with significantly shorter MST (301 ± 64 vs. 626 ± 55 days; p = .0107). In a multivariable analysis, dogs with a CTC spike were 10× more likely to die compared with those without. These results suggest that a spike in CTC frequency precedes detection of metastasis in dogs with OSA and is associated with shorter survival. More frequent enumeration of CTC in a larger cohort of dogs with OSA may be warranted.

Pediatric carcinoid tumors of the lungs: A descriptive analysis.

e22017 Background: From 1973 to 2012, the prevalence of neuroendocrine tumors in children was found to have increased by approximately 6-fold when using the Surveillance Epidemiology, and End Results. While carcinoid tumors in adults are mostly indolent, pediatric carcinoid tumors tend to carry worse prognoses. Our goal for this study is to describe the population of pediatric patients with pulmonary carcinoid tumors. Methods: We used the National Cancer Database to identify pediatric patients diagnosed with carcinoid tumors of the lungs between 2004-2020. Analysis was conducted with SPSS to determine frequency of cases in different demographics. Survival was assessed using Kaplan-Meier curves with significance set at p &lt; 0.05. Results: Of the 125 patients identified, 55% of the patients were male and 45% female. Pulmonary carcinoid tumor patients were predominately white accounting for 80% of all cases. Black patients accounted for 14% of cases. The ages of diagnosis ranged from 3-17 years of age with the mean being 14.5 years of age. The majority of patients were diagnosed during their teenage years–84% were between the ages of 13 and 17 at diagnosis. Only one case was observed in a patient of age 6 or under. The median survival was 89 months. Univariate analysis revealed no significant difference in survival was seen in sex, race, or insurance groups. Charlson-Deyo score, however, did impact survival, where patients with a score of 2 had lower median survival time (36 months) compared to patients with a score of 1 (121 months) or 0 (87 months). Conclusions: Pediatric pulmonary carcinoid tumors are more commonly seen in white patients with most diagnoses occurring during patients’ teenage years (13-17). Age, sex, and race did not have a significant effect on survival although a Charlson-Deyo score of 2 was indicative of a worse prognosis when compared to a score of 1 or 0.

Effects of Postoperative Intravenous Cyclosporine Treatment on the Survival and Functional Performance Status of Patients With Glioblastoma: A Randomized, Triple-Blinded, Placebo-Controlled Clinical Trial

Glioblastoma is associated with low median survival time irrespective of maximal treatment. Previous invitro studies have revealed tumor inhibitory effect of cyclosporine A. However, whether the addition of cyclosporine could improve survival among patients with glioblastoma is unknown. This study aimed to determine the impact of postoperation treatment with cyclosporine on the survival and performance status. In this randomized, triple-blinded, placebo-controlled trial, 118 patients with glioblastoma who underwent surgery were treated with standard chemoradiotherapy regimen. Patients were randomized to receive intravenous cyclosporine for 3days postoperatively or placebo during the same period. The primary endpoint was the short-term effect of intravenous cyclosporine on survival and Karnofsky performance scores. Secondary endpoints were chemoradiotherapy toxicity and neuroimaging features. The overall survival (OS) in the cyclosporine (17.03 ± 5.8, 95% confidence interval: 11-17.37months) group was statistically lower than in the placebo (30.53 ± 4.9, 95% confidence interval: 8-32.3months) groups (P=0.049). However, compared to the placebo group, a statistically higher percentage of patients in the cyclosporine group were alive at 12months follow-up. Also, progression-free survival in the cyclosporine group was significantly prolonged than in the placebo group (6.3 ± 4.07months vs. 3.4 ± 2.98months, P < 0.001). In the multivariate analysis, age <50years (P= 0.022) and gross total resection (P= 0.03) were significantly associated with OS. Our study results demonstrated that administering postoperative cyclosporine does not improve OS and functional performance status. Notably, the survival rate was significantly dependent on the patient age and the extent of glioblastoma resection.

Palliative repeated electroporations of oral tumours in dogs: A case series.

Electrochemotherapy (ECT) is a highly developed treatment for many solid tumours that provides good local control in 80% of neoplasms in dogs. ECT can be used to treat different types of tumours, particularly as an innovative approach for non-resectable masses. As reported in the literature, electroporation-based treatments are safe, simple, fast and cost-effective treatment alternatives for selected oral and maxillofacial tumours not involving the bone in dogs (e.g., small squamous cell carcinoma or malignant melanoma). In this descriptive retrospective paper, the authors describe the outcome of various types of oral tumours treated with ECT as a palliative first line treatment or as a rescue treatment in dogs with local tumour recurrence. Nineteen dogs were included and treated with at least one session of three electroporations coupled with intravenous administration of bleomycin every 21 days. Tumour size, localization, histotype, stage, recurrence, solid tumour response evaluation criteria (RECIST), local toxicity, progression free survival (PFS) and median survival time (MST) were evaluated. The small population did not allow the analysis of the ECT response by comparing different tumour types; further studies with a larger caseload are needed. However, all dogs, despite the low MST, showed a good local response to treatment with a rapid improvement in quality of life from the first ECT application; no side effects attributable to chemotherapy have been detected and toxicity due to the electroporation was minimal and well tolerated in all dogs.

Canine Gastric Cancer: Current Treatment Approaches.

Simple SummaryHuman gastric cancer is a prevalent cancer worldwide with a high mortality rate. Although sharing many other features, the incidence of gastric cancer is lower in dogs than in humans. Surgery is the first-line treatment; however, it is associated with several complications. Nevertheless, chemotherapy to treat canine gastric cancer has not received much attention, probably due to its late diagnosis, fast progression, low median survival time, and very high mortality rate, along with the lack of publications with concrete scientific results. In this review, we explore the pharmacological approach used in treatment of this often-fatal disease. Human gastric cancer (GC) ranks as the fifth most prevalent cancer worldwide, and is the third leading cause of cancer-related death. The incidence of GC is lower in dogs than in humans, accounting for less than 1% of all canine malignancies. In recent years, efforts have been made to understand the pathogenesis of GC and in find an appropriate therapy to maximize curative results, such as adjuvant chemotherapy treatments in addition to surgery. Although surgery is the first-line treatment, it is associated with several complications. In terms of chemotherapeutic intervention, canine gastric cancer has not received much attention, probably due to its late diagnosis, fast progression, low median survival time, and very high mortality rate, along with the lack of publications with concrete scientific results. In this review, we explore canine GC and the pharmacological approach used in the treatment of this often-fatal disease.

Diffusion-weighted imaging as an imaging biomarker for assessing survival of patients with intrahepatic mass-forming cholangiocarcinoma.

Mass-forming cholangiocarcinoma is the most common form of intrahepatic cholangiocarcinoma and is associated with a worse prognosis. This study aimed to assess the role of diffusion-weighted imaging and other imaging features as prognostic markers to predict the survival of patients with intrahepatic mass-forming cholangiocarcinoma (IMCC). The study included patients with pathologically proven IMCC from January 2011 to January 2018. Two radiologists retrospectively reviewed various imaging findings and manually estimated the area of diffusion restriction. Patients were grouped according to their restriction area into (group 1) restriction ≥ 1/3 of the tumor and (group 2) restriction < 1/3 of the tumor. Statistical analysis was performed to assess the relationship between various imaging features and patients' survival. Seventy-three patients were included in the study. IMCC patients with tumor size ≥ 5cm had increased intrahepatic- and peritoneal metastases (p = 039 and p = 0.001 for reader 1 and p = 0.048 and p = 0.057 for reader 2). There was no significant relationship between the diffusion restriction area and tumor size, enhancement pattern, vascular involvement, lymph node metastasis, peritoneal- and distant metastasis. The number of deaths was significantly higher in patients with group 2 restriction (63.6% for group 1 vs. 96.6% for group 2; p = 0.001 for reader 1)(68.2% for group 1 vs. 89.7%% for group 2; p = 0.030 for reader 2). Patients with group 2 restriction had shorter 1- and 3-year survival rates and lower median survival time. Multivariable survival analysis showed two independent prognostic factors relating to poor survival outcomes: peritoneal metastasis (p = 0.04 for reader 1 and p = 0.041 for reader 2) and diffusion restriction < 1/3 (p = 0.011 for reader 1 and p = 0.042 for reader 2). Lymph node metastasis and intrahepatic metastasis were associated with shorter survival in the univariate analysis. However, these factors were non-significant in the multivariate analysis. Restriction diffusion of less than 1/3 and peritoneal metastasis were associated with shorter overall survival of IMCC patients. Other features that might correlate with the outcome are suspicious lymph nodes and multifocal lesions.

Identifying novel mediators of glioblastoma invasion in a hyaluronic acid-based microscale platform with CRISPR screening

Glioblastoma (GBM) is the most common and aggressive form of primary brain cancer, with a devastatingly low median survival time of 15 months despite surgical resection and chemoradiotherapy. GBM is characterized by rapid and highly invasive growth in which individual or collective cancer cells migrate away from the central tumor into the surrounding healthy brain tissue. The diffuse invasion pattern of GBM makes complete surgical resection nearly impossible and inevitably leads to tumor recurrence.

Association of MLH1-93G>A polymorphisms toward lung cancer susceptibility and its association with clinical outcome in North Indian patients treated with platinum-based chemotherapy.

Lung cancer is one of the most prevalent and main causes of malignancy-related deaths worldwide, especially in developed countries. Epidemiological studies have demonstrated that individuals having alterations in a particular gene may have a high risk of developing certain types of cancer. In the present study, 500 Indian lung cancer patients and 500 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism method was used to identify the genotype of enrolled individuals and MedCalc statistical package was used for carrying out statistical analysis. In this study, we found a reduced risk of developing adenocarcinoma in patients harboring variant (P = 0.0007) and combined type genotype (P = 0.008), whereas an increased risk for small-cell lung carcinoma (SCLC) development for those subject harboring GA genotypes (P = 0.03) was also observed. Further, heterozygous type and combined type genotype of heavy smokers for MLH1 polymorphism reported a 2-fold (P = 0.001) and 1.8-fold increased risk toward lung cancer development, respectively (P = 0.007). In case of females, the subjects harboring a variant allele have a significantly reduced risk for lung cancer development (P = 0.0001). For MLH1 polymorphism, reduced risk of developing tumor to T3 or T4 stage was observed (P = 0.04). Moreover, this is the first study reporting overall survival (OS) association for north Indian lung cancer patients with platinum-based doublet chemotherapy; for docetaxel, a three-fold increase in hazard ratio and corresponding low median standard survival time (8.4 months) for mutant and combined type genotype (P = 0.04) was observed. These results suggest that MLH1-93G>A polymorphism is involved in modulating the risk toward lung cancer. Our study also concluded a negative association of OS in patients undergoing carboplatin/cisplatin and docetaxel chemotherapy.

A three serum miRNA panel as diagnostic biomarkers of radiotherapy-related metastasis in non-small cell lung cancer.

Serum microRNAs (miRNAs) have been implicated as noninvasive biomarkers for lung cancer diagnosis. However, there are no sensitive and specific biomarkers for the detection of radiotherapy-related non-small cell lung cancer (NSCLC) metastasis. The present study aimed to investigate the role of three serum miRNAs, namely miRNA (miR)-130a, miR-25 and miR-191*, in diagnosing NSCLC, and their biological functions in radiation-mediated development of metastatic properties in A549 cells. To determine this, serum samples were collected from 84 patients with NSCLC and 42 age- and sex-matched healthy controls. Differential expression of serum miRNAs was analyzed by quantitative PCR. Significant associations between miRNA expression and overall survival of patients with NSCLC were identified using the Cox proportional regression model. A receiver operating characteristic curve was generated to evaluate diagnostic accuracy. The functions of miR-130a, miR-25 and miR-191* in lung cancer cells were studied by transfecting A549 cells with miRNA mimics and inhibitors. The results of the present study demonstrated that the expression levels of miR-130a, miR-25 and miR-191* in the serum of patients with NSCLC were increased compared with those in healthy controls, and these increases were associated with advanced age (≥60 years), radiotherapy, histological type (squamous carcinoma), low survival rate and low median survival time. Additionally, irradiation induced the upregulation of miR-130a, miR-25 and miR-191* expression in A549 cells in vitro and in a xenograft mouse model. Irradiation also promoted the invasiveness of A549 cells in vitro and metastasis in vivo. In conclusion, miR-130a, miR-25 and miR-191* may be potential biomarkers for the diagnosis of patients with NSCLC and may serve oncogenic roles in radiation-mediated metastasis of NSCLC.

Application prospect of peptide-modified nano targeting drug delivery system combined with PD-1/PD-L1 based immune checkpoint blockade in glioblastoma

Glioblastoma (GBM) is a type of primary malignant brain tumor with low median survival time, high recurrence rate and poor prognosis. The blood-brain barrier (BBB) and the diffuse infiltration of invasive GBM cells lead to a lower efficacy of traditional treatment. Recently, nanocarriers have become a promising method of brain drug delivery due to their ability to effectively cross the BBB. Especially, the peptide-modified nanocarriers can enhance the permeability, targeting and efficacy of chemotherapeutic agents against GBM. Moreover, the clinical application of immune checkpoint blockade (ICB) therapy in cancer treatment has attracted increasing attention, and the programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) monoclonal antibodies are considered to be a possible therapy for GBM. Consequently, we review the advances both in peptide-modified nano targeted drug delivery system and PD-1/PD-L1 based ICB in GBM treatment, and propose a new strategy combining the two methods, which may provide a novel approach for GBM treatment.

Comparing Total Medical Costs between Patients Receiving Direct Oral Anticoagulants Versus Warfarin for the Treatment of Atrial Fibrillation: Evidence from the VA

Atrial fibrillation (AFib) is the second most common cardiovascular condition affecting up to 6.1 million individuals in the United States. Treatment of AFib focuses on preventing blood clots to reduce stroke risk. Traditionally, warfarin, a vitamin‐k antagonist, has been used to reduce stroke risk by two‐thirds. However, warfarin requires regular laboratory monitoring to ensure safety and efficacy, and may be cumbersome for patients. Newer direct oral anticoagulants (DOACs) are an alternative treatment and do not require laboratory monitoring due to their more predictable pharmacokinetics. DOACs are either noninferior or superior to warfarin on a variety of outcomes and may be cost‐effective for certain patient populations. Much of the evidence demonstrating benefits of DOACs over warfarin have been in clinical trial settings, which may have limited generalizability to real‐world practice. For example, patients enrolled in the Veterans Affairs (VA) Health care System have increased burden of illness and greater socioeconomic challenges relative to other populations. This study examined whether advantages of DOACs found in prior trials translated to the VA population by comparing total downstream costs between AFib patients treated with warfarin and DOACs.Using administrative data from VA and Medicare, we examined total medical costs (inpatient and outpatient costs incurred in VA and Medicare) over three years following initiation of pharmacological treatment for AFib. To address potential informative censoring, we applied a multipart estimator that extends traditional two‐part models to separate differences between groups due to effects on survival and cost accumulation. This estimator requires modeling the probability of surviving to each time period, hazard probability, expected patient‐level costs over period t conditional on death and expected costs over period t conditional on surviving the full period. We applied inverse probability weighting to address imbalance in characteristics between patients treated with warfarin and DOACs. Weights were estimated as a function of 99 baseline patient and clinic characteristics using boosted regression trees allowing for complex interactions between predictors.75 547 veterans dually enrolled in VA and fee‐for‐service Medicare who had a new diagnosis for AFib and initiated warfarin or DOAC treatment between 2011 and 2015The majority of patients initiated warfarin (64%) with the remainder initiating the DOACs apixaban (14%), dabigatran (12%), and rivaroxaban (9%). Mean annual costs in the first through third years of the follow‐up period were $33 364 (SD = $64 493), $18 379 (SD = $38 089), and $17 081 (SD = $38 725), respectively. In adjusted analysis, patients receiving warfarin had lower median survival time (−0.107 years, 95% confidence interval (CI) = −0.213 to −0.011) and higher annual cost conditional on death ($12 873, 95% CI = $8681 to $17 065) and surviving the full year ($9163, 95% CI = $8311 to $10 015). Total three‐year costs were higher among patients receiving warfarin ($22 718, 95% CI = $19 851 to $25 478).VA AFib patients initiating warfarin compared to DOACs incurred significantly higher downstream costs, even after accounting for a greater likelihood of death.The benefits of DOACs found in prior clinical trials appear to also be present among this patient population, suggesting these drugs may be the preferred option for treatment of AFib in elderly VA patients.Department of Veterans Affairs.

Clinical significance of lymph node micrometastasis in T1N0 early gastric cancer.

To investigate the significance of lymph node micrometastasis in T1N0 early gastric cancer. Lymph node micrometastasis may be a key mechanism in the recurrent T1N0 EGC patients after surgical treatment. It's unknow whether it is safe to leave the lymph nodes with micrometastasis untreated after ESD. A total of 106 T1N0 EGC patients were enrolled in this study. Immunohistochemical technique with CAM5.2 was employed to detect lymph node micrometastasis, and Immunohistochemical with D2-40 was used to detect the lymphatic vessels. Prognostic significance of lymph node micrometastasis and the relationship of lymph nodes micrometastasis with Clinicopathological features were analyzed. Twenty-two of the 106 T1N0 EGC cases were detected with lymph nodes micrometastasis, with the detection rate of 20.8%. The median survival time of the group with positive lymph nodes micrometastasis was lower than that of the group with negative micrometastasis, 48 vs 60 months. The incidence of lymph nodes micrometastasis in submucosal T1N0 EGC was 23.9%, while no micrometastasis was found in the mucosal T1N0 EGC. Of all the 30 cases according with the expanded ESD indications, six patients were found with lymph nodes micrometastasis. The occurrence of lymph node micrometastasis was common in T1N0 EGC. The cases with positive lymph nodes micrometastasis showed a lower median survival time than those with negative micrometastasis. lymph nodes micrometastasis incidence was higher in the submucosal ECG than in the mucosal ECG. lymph nodes micrometastasis was also found in the cases according to the expanded ESD indications.

Outcomes of duodenal stenting: Experience in a French tertiary center with 220 cases

IntroductionEndoscopic stenting for malignant gastroduodenal outlet obstruction (MGOO) is described as ineffective and not long-lasting despite a few favorable studies. This study aimed to evaluate the clinical outcomes of a large series of patients in a tertiary center. MethodsA single-center retrospective study was performed using data collected from all patients who received palliative duodenal self-expandable metal stents between January 2011 and December 2016. The primary endpoints were patient diet after the first duodenal procedure (Gastric Outlet Obstruction Scoring System, GOOSS) and clinical success. The secondary endpoints were the median patency duration (calculated according to the Kaplan–Meier method) and the cumulative incidence of reintervention. ResultsTwo-hundred twenty patients were included. The increase in the GOOSS score was significant (p < 0.001), and the clinical success rate was 86.3%. The median estimated patency duration was 9.0 months [6.5–29.1]. Patients with pancreatic adenocarcinoma had significantly longer patency durations (p = 0.02). The estimated cumulative probability of a second duodenal procedure after 4 months was 13%. ConclusionsIn this large series of patients who underwent duodenal stenting for MGOO, we observed significant changes in GOOSS scores, a relatively long patency duration compared to findings in previous series, and a low probability of subsequent duodenal procedures, primarily due to a low median overall survival time (4 months).

Pilot study evaluating the monitoring of canine diabetes mellitus in primary care practice

ObjectivesThis study aimed to describe how canine diabetes mellitus (CDM) is monitored in primary care practice (PCP) and to report outcomes.DesignRetrospective case review.SettingPCP.Participants40 dogs of 22 different pedigrees and five...

AMPK Inhibition Suppresses the Malignant Phenotype of Pancreatic Cancer Cells in Part by Attenuating Aerobic Glycolysis.

Pancreatic cancer is a highly aggressive tumor characterized by enhanced aerobic glycolysis. AMP-activated protein kinase (AMPK), which is identified as a well-known regulator of glycolysis, plays an essential role in tumorigenesis. In the present study, we aim to explore the function of AMPK in pancreatic cancer cells and attempt to clarify the possible underlying mechanism. The Cancer Genome Atlas (TCGA) data showed that elevated AMPK expression highly correlated with lower median survival time. In an in vitro study, inhibition of AMPK blocked the proliferation, migration, and invasion ability of four cell lines under normoxia and hypoxia. Additionally, AMPK suppression led to cell cycle arrest and remarkably induced apoptosis. Furthermore, the lactic acid content, ATP content, and the glucose consumption rate were significantly reduced in all four cell lines under different conditions, accompanied by down-regulation of glycolytic biomarkers including phosphorylated mammalian target of rapamycin (p-mTOR)/total mTOR (t-mTOR), Pyruvate kinase M2 (Pkm2), and Hexokinase 2 (Hk2). Collectively, our data showed that AMPK activation is highly involved in pancreatic cancer progression and exerts its pro-tumorigenic functions partly by sustaining glycolytic activity. Hence, AMPK is expected to be a potential therapeutic target for pancreatic cancer.

Clinical characteristics and prognostic factors of esophageal carcinoma associated with multiple primary carcinomas: a report of 268 cases

Background: To evaluate the clinical characteristics and prognostic factors of esophageal carcinoma (EC) with multiple primary carcinomas (ECWMPC). Methods: Clinical and survival data of 268 ECWMPC patients with two different primary carcinomas and 9,101 individual EC patients taken from hospital records dating from January 1996 to December 2012 were analyzed retrospectively. Results: There were a total of 11,066 EC patients treated over this period of which 330 patients met the diagnostic criteria of ECWMPC. Two hundred and sixty-eight patients who had two different primary carcinomas and survival data were recruited in this analysis. The median age of the first carcinoma occurrence was 59 (31 to 85) years old, and the median age of the second carcinoma occurrence was 62 (32 to 86) years old, with a male to female ratio of 6:1. The predilection sites were located in the head and neck, followed by the gastric-esophageal junction. For the subgroup of synchronous ECWMPC (S-ECWMPC) and metachronous ECWMPC (M-ECWMPC), head and neck remain the popular site of S-ECWMPC but cardiac became the top of the M-ECWMPC. More breast and colon rectum disease were found in S-ECWMPC patients. The ECWMPC patients had a significantly lower median survival time (MST) and 1, 3, and 5 years overall survival (OS) than the single EC patients [12.4 months and 51.8%, 21.9%, 14.7% vs . 17.0 months and 59.4%, 31.3%, and 23.9% (P vs . 13.9 months and 56.2%, 25.6%, 19.5% (P=0.001)]. Within the S-ECWMPC group, patients who only received radiotherapy and/or chemotherapy (RoC) (n=52) had a shorter/poorer survival time (MST and 1, 3, and 5 years OS are 9.8 months, 44.2%, 8.7%, 3.2%) compared to patients who received surgery (n=43) (MST and 1, 3, and 5 years OS are 16.4 months, 64.8%, 33.3%, 18.6%) (P=0.031), but a longer survival time compared to patients who had no treatment (n=20) (MST and 1, 3, and 5 years OS are 4.1 months, 10.0%, 5.0%, and 0%)(P=0.002). Within the M-ECWMPC group, patients who had received surgery (n=103) had a longer survival time than patients who had only received RoC (n=38) (MST 22.5 vs . 10.6 months, P=0.026). Among the 103 M-ECWMPC patients who had received surgery, 55 of them had an esophagus resection, whose OS was similar to those 3,633 operated EC patients (MST 31 months vs . 30 months, P=0.905). Within the M-ECWMPC group, patients with greater than 3 years interval time of diagnosis (ITD) had a better prognosis compared to patients with less than 3 years ITD (MST 24.8 vs . 13.2 months, P=0.021) There is no statistical difference in the prognosis between M-ECWMPC patients and Single EC patients (P=0.585). Conclusions: ECWMPC is not rare among EC patients. There is more cardiac in the M-ECWMPC patients and more Breast and Colon rectum disease were found in S-ECWMPC patients. Prognosis of M-ECWMPC patients was better than that of the S-ECWMPC patients. M-ECWMPC patients with a more than 3 years ITD had a better prognosis. In M-ECWMPC patients, esophageal surgery can acquire better survival benefits than other treatments. Surgery is highly recommended for ECWMPC patients.

Endophytic colonisation of tomato by the entomopathogenic fungus Beauveria bassiana: the use of different inoculation techniques and their effects on the tomato leafminer Tuta absoluta (Lepidoptera: Gelechiidae)

Abstract Fungal entomopathogens can naturally regulate populations of various insects. The entomopathogen Beauveria bassiana (Bals.-Criv.) Vuill. is also able to endophytically colonize different plants. Endophytic colonization by entomopathogens may provide a source of indirect interactions between fungi and insects and has been associated with the ability of the fungus to control insect pests. The tomato leaf miner, Tuta absoluta (Meyrick) is considered one of the most devastating pests of tomato (Solanum lycopersicum L.) and its difficult control is due to its miner habit, short life cycle, and high reproductive capacity. The aims of this study were: (i) to use three different techniques, i.e. leaf spraying, seed immersion and root dipping, for the endophytic inoculation of B. bassiana in tomato plants; and (ii) to assess the effect of B. bassiana on tomato leaf consumption and mortality of T. absoluta after inoculation. The percentage of colonization by B. bassiana was assessed 7, 14 and 28 days after inoculation. All inoculation techniques employed allowed the recovery of B. bassiana, although our results showed significant differences between techniques. Leaf spraying was the most effective, with the highest percentage of colonization recorded 7 days after inoculation. We also evaluated (i) the effect on the mortality of T. absoluta by direct contact with conidia of B. bassiana, and (ii) the effect on tomato leaf consumption and mortality by indirect contact through ingestion of inoculated plant tissues with B. bassiana. Mortality bioassays showed that B. bassiana infected T. absoluta, either by direct contact or indirectly, via ingestion of inoculated tomato leaves. Direct contact showed a higher percentage of mortality and a lower median survival time (MST) than indirect contact. Significant differences in the mortality percentages of T. absoluta after exposure with B. bassiana were found among the treatments and the control. Our results suggest that the endophytic inoculation of B. bassiana in tomato crops provides the basis for further investigation, which should focus on the virulence of the endophytic B. bassiana against T. absoluta.