Dissecting the Lymphatic System to Predict Melanoma Metastasis

Melanoma is the most lethal form of skin cancer in the United States. Current American Joint Committee on Cancer (AJCC) staging uses Breslow depth and ulceration as the two primary tumor factors that predict metastatic risk in cutaneous melanoma. Early disease stages are generally associated with high survival rates. However, in some cases, patients with thin melanomas develop advanced disease, suggesting other factors may contribute to the metastatic potential of an individual patient’s melanoma. This review focuses on the role of the lymphatic system in the metastasis of cutaneous melanoma, from recent discoveries in mechanisms of lymphangiogenesis to elements of the lymphatic system that ultimately may aid clinicians in determining which patients are at highest risk. Ultimately, this review highlights the need to integrate pathological, morphological, and molecular characteristics of lymphatics into a “biomarker” for metastatic potential.

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Standards for Resuscitation After Cardiac Surgery

Critical Care Nurse ◽

10.4037/ccn2015652 ◽

2015 ◽

Vol 35 (2) ◽

pp. 30-38 ◽

Cited By ~ 5

Author(s):

S. Jill Ley

Keyword(s):

United States ◽

Cardiac Arrest ◽

Cardiac Surgery ◽

Heart Surgery ◽

Life Support ◽

Survival Rates ◽

Advanced Life Support ◽

The United States ◽

High Survival ◽

Essential Components

Of the 250 000 patients who undergo major cardiac operations in the United States annually, 0.7% to 2.9% will experience a postoperative cardiac arrest. Although Advanced Cardiac Life Support (ACLS) is the standard approach to management of cardiac arrest in the United States, it has significant limitations in these patients. The European Resuscitation Council (ERC) has endorsed a new guideline specific to resuscitation after cardiac surgery that advises important, evidence-based deviations from ACLS and is under consideration in the United States. The ACLS and ERC recommendations for resuscitation of these patients are contrasted on the basis of the essential components of care. Key to this approach is the rapid elimination of reversible causes of arrest, followed by either defibrillation or pacing (as appropriate) before external cardiac compressions that can damage the sternotomy, cautious use of epinephrine owing to potential rebound hypertension, and prompt resternotomy (within 5 minutes) to promote optimal cerebral perfusion with internal massage, if prior interventions are unsuccessful. These techniques are relatively simple, reproducible, and easily mastered in Cardiac Surgical Unit–Advanced Life Support courses. Resuscitation of patients after heart surgery presents a unique opportunity to achieve high survival rates with key modifications to ACLS that warrant adoption in the United States.

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Prediction and Analysis of Skin Cancer Progression using Genomics Profiles of Patients

Scientific Reports ◽

10.1038/s41598-019-52134-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 9

Author(s):

Sherry Bhalla ◽

Harpreet Kaur ◽

Anjali Dhall ◽

Gajendra P. S. Raghava

Keyword(s):

Cancer Progression ◽

Cutaneous Melanoma ◽

Prediction Models ◽

Survival Rates ◽

Validation Dataset ◽

Support Vector ◽

Melanoma Metastasis ◽

Primary Tumors ◽

Genomic Features ◽

Optimal Therapeutic Strategy

Abstract The metastatic Skin Cutaneous Melanoma (SKCM) has been associated with diminished survival rates and high mortality rates worldwide. Thus, segregating metastatic melanoma from the primary tumors is crucial to employ an optimal therapeutic strategy for the prolonged survival of patients. The SKCM mRNA, miRNA and methylation data of TCGA is comprehensively analysed to recognize key genomic features that can segregate metastatic and primary tumors. Further, machine learning models have been developed using selected features to distinguish the same. The Support Vector Classification with Weight (SVC-W) model developed using the expression of 17 mRNAs achieved Area under the Receiver Operating Characteristic (AUROC) curve of 0.95 and an accuracy of 89.47% on an independent validation dataset. This study reveals the genes C7, MMP3, KRT14, LOC642587, CASP7, S100A7 and miRNAs hsa-mir-205 and hsa-mir-203b as the key genomic features that may substantially contribute to the oncogenesis of melanoma. Our study also proposes genes ESM1, NFATC3, C7orf4, CDK14, ZNF827, and ZSWIM7 as novel putative markers for cutaneous melanoma metastasis. The major prediction models and analysis modules to predict metastatic and primary tumor samples of SKCM are available from a webserver, CancerSPP (http://webs.iiitd.edu.in/raghava/cancerspp/).

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Survival and persistence of tricolored bats hibernating in Arkansas mines

Journal of Mammalogy ◽

10.1093/jmammal/gyaa016 ◽

2020 ◽

Vol 101 (2) ◽

pp. 535-543 ◽

Cited By ~ 1

Author(s):

Roger W Perry ◽

Phillip N Jordan

Keyword(s):

United States ◽

Endemic Area ◽

Survival Rates ◽

The United States ◽

Abandoned Mines ◽

Eastern North America ◽

High Survival ◽

Ouachita Mountains ◽

Apparent Survival ◽

White Nose Syndrome

Abstract White-nose syndrome (WNS) has caused large declines in bat populations across eastern North America, making information on demographics of affected species critical to determining their risk for extinction. We used Cormack–Jolly–Seber models to estimate apparent survival rates of hibernating tricolored bats (Perimyotis subflavus) for 5 years in four small abandoned mines in the Ouachita Mountains of Arkansas, located within the WNS endemic area of the United States. Populations in individual mines varied greatly in survival rates, with one mine displaying annual survival rates as high as 0.706 and another as low as 0.101. Differences in survival among bats in different mines could not definitively be attributed to WNS, but may have varied based on a combination of WNS, disturbance, mine climate, and other unknown factors. Further, some hibernacula may have served as temporary winter shelter for young transient males. Sites housing small colonies of hibernating bats may result in high survival rates despite WNS, and protecting these smaller sites may be important for overall species perseverance.

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Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma

JCO Precision Oncology ◽

10.1200/po.20.00119 ◽

2021 ◽

pp. 589-601

Author(s):

Eddy C. Hsueh ◽

James R. DeBloom ◽

Jonathan H. Lee ◽

Jeffrey J. Sussman ◽

Kyle R. Covington ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profile ◽

Expression Profile ◽

Distant Metastasis ◽

Cutaneous Melanoma ◽

Stage I ◽

Free Survival ◽

Metastatic Risk ◽

Ajcc Staging

PURPOSE Current guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many of these patients develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment of these patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high (class 2). Prospective analysis of CM outcomes was performed to test the hypotheses that the 31-GEP provides prognostic value for patients with stage I-III CM, and that patients with stage I-IIA melanoma and class 2 31-GEP results have metastatic risk similar to patients for whom surveillance is recommended. MATERIALS AND METHODS Two multicenter registry studies, INTEGRATE (ClinicalTrials.gov identifier: NCT02355574 ) and EXPAND (ClinicalTrials.gov identifier: NCT02355587 ), were initiated under institutional review board approval, and 323 patients with stage I-III CM and median follow-up time of 3.2 years met inclusion criteria. Primary end points were 3-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS The 31-GEP was significant for RFS, DMFS, and OS in a univariate analysis and was a significant, independent predictor of RFS, DMFS, and OS in a multivariable analysis. GEP class 2 results were significantly associated with lower 3-year RFS, DMFS, and OS in all patients and those with stage I-IIA disease. Patients with stage I-IIA CM and a class 2 result had recurrence, distant metastasis, and death rates similar to patients with stage IIB-III CM. Combining 31-GEP results and AJCC staging enhanced sensitivity over each approach alone. CONCLUSION These data provide a rationale for using the 31-GEP along with AJCC staging, and suggest that patients with stage I-IIA CM and a class 2 31-GEP signature may be candidates for more intense follow-up.

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MyoD-Cre driven alterations in K-Ras and p53 lead to a mouse model with histological and molecular characteristics of human rhabdomyosarcoma with direct translational applications

10.1101/2021.06.15.448607 ◽

2021 ◽

Author(s):

Kengo Nakahata ◽

Brian W. Simons ◽

Enrico Pozzo ◽

Ryan Shuck ◽

Lyazat Kurenbekova ◽

...

Keyword(s):

Mouse Model ◽

Survival Rates ◽

Metastatic Potential ◽

Human Cell Line ◽

Genetically Engineered ◽

Treatment Modalities ◽

Molecular Characteristics ◽

Term Survival ◽

Primary Tumors ◽

Genetically Engineered Mouse Model

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, with overall long-term survival rates of about 65-70%. Thus, additional molecular insights and representative models are critical for further identifying and evaluating new treatment modalities. Using MyoD-Cre mediated introduction of mutant K-RasG12D and perturbations in p53 we have developed a novel genetically engineered mouse model (GEMM) for RMS. Specifically, we directly crossed mice expressing MyoD promoter-regulated Cre-recombinase with germline p53Flox or Lox-Stop-Lox (LSL) knock-in alleles expressing oncogenic p53R172H and/or K-RasG12D mutants. The anatomic sites of primary RMS development observed in these mice recapitulated human disease, with the most frequent sites of tumor growth seen in the head, neck, extremities, and abdomen. We have confirmed RMS histology and diagnosis through hematoxylin and eosin (H&E) staining, as well as positive immunohistochemistry (IHC) staining for desmin, myogenin, and phosphotungstic acid hematoxylin (PTAH). We established cell lines from several of the GEMM tumors with the ability to engraft and develop tumors in immunocompetent mice with similar histological and staining features as the primary tumors. Furthermore, injection of syngeneic RMS lines via tail vein had high metastatic potential to the lungs. Transcriptomic analyses of p53R172H/K-RasG12D GEMM-derived tumors showed evidence of high molecular homology with human RMS. Specifically, we noted alterations in gene ontologies including immune response, metabolism and mRNA processing. Finally, pre-clinical use of these murine RMS lines demonstrated similar therapeutic responsiveness to relevant chemotherapy and targeted therapies as human cell line models.

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Cognitive decline in patients with prostate cancer: study protocol of a prospective cohort, NEON-PC

BMJ Open ◽

10.1136/bmjopen-2020-043844 ◽

2021 ◽

Vol 11 (2) ◽

pp. e043844

Author(s):

Natalia Araujo ◽

Samantha Morais ◽

Ana Rute Costa ◽

Raquel Braga ◽

Ana Filipa Carneiro ◽

...

Keyword(s):

Prostate Cancer ◽

Cognitive Decline ◽

Cognitive Performance ◽

Androgen Deprivation Therapy ◽

Survival Rates ◽

Cardiovascular Complications ◽

Androgen Deprivation ◽

High Survival ◽

The Impact

IntroductionProstate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline.MethodsParticipants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants’ cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist.Ethics and disseminationThe study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.

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Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML

Biochemical Society Transactions ◽

10.1042/bst20190221 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1307-1325 ◽

Cited By ~ 1

Author(s):

Caroline Busch ◽

Helen Wheadon

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Bone Morphogenetic Proteins ◽

Kinase Inhibitor ◽

Survival Rates ◽

High Survival ◽

Bone Marrow Niche ◽

Matrix Deposition ◽

Bmp Receptors ◽

Number Of Patients

Abstract Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, there are BCR-ABL1-independent mechanisms exploited to sustain the survival of a small cell population of leukaemic stem cells (LSCs). In CML, LSCs display many features akin to haemopoietic stem cells, namely quiescence, self-renewal and the ability to produce mature progeny, this all occurs through intrinsic and extrinsic signals within the specialised microenvironment of the bone marrow (BM) niche. One important avenue of investigation in CML is how the disease highjacks the BM, thereby remodelling this microenvironment to create a niche, which enables LSC persistence and resistance to TKI treatment. In this review, we explore how changes in growth factor levels, in particular, the bone morphogenetic proteins (BMPs) and pro-inflammatory cytokines, impact on cell behaviour, extracellular matrix deposition and bone remodelling in CML. We also discuss the challenges in targeting LSCs and the potential of dual targeting using combination therapies against BMP receptors and BCR-ABL1.

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Survival Rate of 1008 Short Dental Implants with 21 Months of Average Follow-Up: A Retrospective Study

Journal of Clinical Medicine ◽

10.3390/jcm9123943 ◽

2020 ◽

Vol 9 (12) ◽

pp. 3943

Author(s):

João Caramês ◽

Ana Catarina Pinto ◽

Gonçalo Caramês ◽

Helena Francisco ◽

Joana Fialho ◽

...

Keyword(s):

Retrospective Study ◽

Survival Rate ◽

Dental Implants ◽

Cox Regression ◽

Survival Rates ◽

High Survival ◽

Implant Survival ◽

Posterior Maxilla ◽

Clinical Records

This retrospective study evaluated the survival rate of short, sandblasted acid-etched surfaced implants with 6 and 8 mm lengths with at least 120 days of follow-up. Data concerning patient, implant and surgery characteristics were retrieved from clinical records. Sandblasted and acid-etched (SLA)-surfaced tissue-level 6 mm (TL6) or 8 mm (TL8) implants or bone-level tapered 8 mm (BLT8) implants were used. Absolute and relative frequency distributions were calculated for qualitative variables and mean values and standard deviations for quantitative variables. A Cox regression model was performed to verify whether type, length and/or width influence the implant survival. The cumulative implant survival rate was assessed by time-to-event analyses (Kaplan–Meier estimator). In all, 513 patients with a mean age of 58.00 ± 12.44 years received 1008 dental implants with a mean follow-up of 21.57 ± 10.77 months. Most implants (78.17%) presented a 4.1 mm diameter, and the most frequent indication was a partially edentulous arch (44.15%). The most frequent locations were the posterior mandible (53.97%) and the posterior maxilla (31.55%). No significant differences were found in survival rates between groups of type, length and width of implant with the cumulative rate being 97.7% ± 0.5%. Within the limitations of this study, the evaluated short implants are a predictable option with high survival rates during the follow-up without statistical differences between the appraised types, lengths and widths.

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