Lumbar disk 3D modeling from limited number of MRI axial slices

This paper studies the problem of clinical MRI analysis in the field of lumbar intervertebral disk herniation diagnosis. It discusses the possibility of assisting radiologists in reading the patients MRI images by constructing a 3D model for the region of interest using simple computer vision methods. We use axial MRI slices of the lumbar area. The proposed framework works with a very small number of MRI slices and goes through three main stages. Namely, the region of interest extraction and enhancement, inter-slice interpolation, and 3D model construction. We use the Marching Cubes algorithm to construct the 3D model of the the region of interest. The validation of our 3D models is based on a radiologist’s analysis of the models. We tested the proposed 3D model construction on 83 cases and We have a 95% accuracy according to the radiologist evaluation. This study shows that 3D model construction can greatly ease the task of the radiologist which enhances the working experience. This leads eventually to more accurate and easy diagnosis process

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Cytotoxicity and Selectivity in Skin Cancer by SapC-DOPS Nanovesicles

Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceed 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using several in vitro and in vivo skin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4 % tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections

Targeting and Cytotoxicity of SapC-DOPS Nanovesicles in Pancreatic Cancer

<div><p>Only a small number of promising drugs target pancreatic cancer, which is the fourth leading cause of cancer deaths with a 5-year survival of less than 5%. Our goal is to develop a new biotherapeutic agent in which a lysosomal protein (saposin C, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS) are assembled into nanovesicles (SapC-DOPS) for treating pancreatic cancer. A distinguishing feature of SapC-DOPS nanovesicles is their high affinity for phosphatidylserine (PS) rich microdomains, which are abnormally exposed on the membrane surface of human pancreatic tumor cells. To evaluate the role of external cell PS, <i>in vitro</i> assays were used to correlate PS exposure and the cytotoxic effect of SapC-DOPS in human tumor and nontumorigenic pancreatic cells. Next, pancreatic tumor xenografts (orthotopic and subcutaneous models) were used for tumor targeting and therapeutic efficacy studies with systemic SapC-DOPS treatment. We observed that the nanovesicles selectively killed human pancreatic cancer cells <i>in vitro</i> by inducing apoptotic death, whereas untransformed cells remained unaffected. This <i>in vitro</i> cytotoxic effect correlated to the surface exposure level of PS on the tumor cells. Using xenografts, animals treated with SapC-DOPS showed clear survival benefits and their tumors shrank or disappeared. Furthermore, using a double-tracking method in live mice, we showed that the nanovesicles were specifically targeted to orthotopically-implanted, bioluminescent pancreatic tumors. These data suggest that the acidic phospholipid PS is a biomarker for pancreatic cancer that can be effectively targeted for therapy utilizing cancer-selective SapC-DOPS nanovesicles. This study provides convincing evidence in support of developing a new therapeutic approach to pancreatic cancer.</p></div

Effect of SapC-DOPS nanovesicles on pancreatic tumor growth.

<p>Subcutaneous tumors (MiaPaCa-2 cell line) treated with SapC-DOPS nanovesicles had significantly reduced tumor end-volume (A) and end-weight (B) compared to controls.</p

Localization of fluorescently labeled SapC-DOPS in normal mouse tissue.

<p>The organ distribution of fluorescently labeled SapC-DOPS 1, 12 and 24 hours after injection is shown in (A), (B), and (C) respectively. The liver and spleen were the only organs that had detectable fluorescent signal 1 and 12 hours post-injection for all animals. This signal was no longer present by 24 hours post-injection. The lung, heart, and kidney showed no detectable fluorescent signal. SapC = 3.2 mg/kg, DOPS = 1.8 mg/kg, CVM = 6 µM.</p

Survival of SapC-DOPS-treated mice with orthotopically implanted pancreatic tumors.

<p>(A) Survival of SapC-DOPS-treated mice was significantly greater than controls. Insert panel: bioluminescence confirms hidden implanted pancreatic tumor on live imaging (mouse on right). (B) Tumor weight at time of death is shown. No tumor was noted in the four surviving mice at post-treatment day 110, as documented by the absence of bioluminescence in those mice (insert panel).</p

Targeting of subcutaneous tumor xenografts by fluorescently labeled SapC-DOPS nanovesicles.

<p>Heterotopic MiaPaCa-2 tumors (circled) were generated by subcutaneous injection in the upper flank of nude mice. (A) Mice 1 & 2 were tumor-bearing mice, injected with fluorescently labeled SapC-DOPS nanovesicles; Mouse 3 was non-tumor-bearing, PBS injected. Mice 1 and 2 both demonstrate localization of the fluorescent label to the tumor site. Fluorescence also localizes to the liver by 2 hours, but is gone by 24 hours. (B) Tumor-bearing mice 4, 5, and 6 were injected with non-complexed SapC and fluorescently labeled DOPS, fluorescently labeled DOPS only, and PBS, respectively. There is no fluorescence localized to tumor in any of these mice. Like the SapC-DOPS (in mice 1 and 2), non-complexed SapC and fluorescently labeled DOPS and fluorescently labeled DOPS alone (in mice 4 and 5, respectively) did localize to the liver, but quickly dissipated (C) Subcutaneous tumors created using cfPac1-Luc3 pancreatic tumor cells that were and were not pretreated with PS-specific binding proteins (Lactadherin-C2 [left upper panel] and Beta-GP-1 [left lower panel]) display bioluminescence on live imaging. After administration of CVM fluorescently labeled SapC-DOPS nanovesicles, the tumors that were not pretreated demonstrated fluorescence, while the tumors that had been pretreated did not demonstrate any fluorescence (right upper and lower panels). (D) Presence of bioluminescence (upper panel) confirms presence of orthotopic pancreatic tumor, and co-localized fluorescence (bottom panel) confirms targeting by fluorescently labeled SapC-DOPS nanovesicles.</p