Dataset Information

A new mild hyperthermia device to treat vascular involvement in cancer surgery.

ABSTRACT: Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature. Herein, we present a novel intra-operative device created to facilitate a uniform and mild heating profile to cause hyperthermic destruction of vessel-encasing tumors while safeguarding the encased vessel. We use pancreatic ductal adenocarcinoma as an in vitro and an in vivo cancer model for these studies as it is a representative model of a tumor that commonly involves major mesenteric vessels. In vitro data suggests that mild hyperthermia (41-46 °C for ten minutes) is an optimal thermal dose to induce high levels of cancer cell death, alter cancer cell's proteomic profiles and eliminate cancer stem cells while preserving non-malignant cells. In vivo and in silico data supports the well-known phenomena of a vascular heat sink effect that causes high temperature differentials through tissues undergoing hyperthermia, however temperatures can be predicted and used as a tool for the surgeon to adjust thermal doses delivered for various tumor margins.

SUBMITTER: Ware MJ

PROVIDER: S-EPMC5595878 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A new mild hyperthermia device to treat vascular involvement in cancer surgery.

Ware Matthew J MJ Nguyen Lam P LP Law Justin J JJ Krzykawska-Serda Martyna M Taylor Kimberly M KM Cao Hop S Tran HST Anderson Andrew O AO Pulikkathara Merlyn M Newton Jared M JM Ho Jason C JC Hwang Rosa R Rajapakshe Kimal K Coarfa Cristian C Huang Shixia S Edwards Dean D Curley Steven A SA Corr Stuart J SJ

Scientific reports 20170912 1

Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature. Herein, we present a novel intra-operative device created to facilitate a uniform and mi ...[more]

PMID: 28900126

Similar Datasets

Project description:The abnormal tumor vasculature presents a major challenge to the adequate delivery of chemotherapeutics, often limiting efficacy. We developed a nanoparticle-based technique to deliver localized mild hyperthermia (MHT) used to transiently alter tumor vascular transport properties and enhance transport of macromolecules into tumor interstitium. The strategy involved administering and localizing accumulation of stealth gold nanorods (GNRs, 103 μg of GNRs/g of tumor), and irradiating tumor with a low-photon laser flux (1 W/cm(2)) to generate MHT. The treatment increased vascular permeability within 24 h after treatment, allowing enhanced transport of macromolecules up to 54 nm in size. A mathematical model is used to describe changes in tumor mass transport properties where the rate of macromolecular exchange between interstitial and vascular region (R) and maximum dye enhancement (Ymax) of 23-nm dextran dye is analytically solved. During enhanced permeability, R increased by 200% while Ymax increased by 30% relative to untreated group in pancreatic CAPAN-1 tumors. MHT treatment also enhanced transport of larger dextran dye (54 nm) as assessed by intravital microscopy, without causing occlusive cellular damage. Enhanced vascular transport was prolonged for up to 24 h after treatment, but reversible with transport parameters returning to basal levels after 36 h. This study indicates that localized mild hyperthermia treatment opens a transient time-window with which to enable and augment macromolecule transport and potentially improve therapeutic efficacy. From the clinical editor: In this study, local intra-tumor mild hyperthermia is induced using a nanoparticle-based approach utilizing stealth gold nanorods and irradiating the tumor with low-photon laser flux, resulting in locally increased vascular permeability enabling enhanced delivery of therapeutics, including macromolecules up to 54 nm in size. Similar approaches would be very helpful in addressing treatment-resistant malignancies in clinical practice.

Project description:Traumatic brain injury (TBI) is one of the leading causes of mortality and disability around the world. Mild TBI (mTBI) makes up approximately 80% of reported cases and often results in transient psychological abnormalities and cognitive disruption. At-risk populations for mTBI include athletes and other active individuals who may sustain repetitive concussive injury during periods of exercise and exertion when core temperatures are elevated. Previous studies have emphasized the impact that increased brain temperature has on adverse neurological outcomes. A lack of diagnostic tools to assess concussive mTBI limits the ability to effectively identify the post-concussive period during which the brain is uniquely susceptible to damage upon sustaining additional injury. Studies have suggested that a temporal window of increased vulnerability that exists corresponds to a period of injury-induced depression of cerebral glucose metabolism. In the current study, we sought to evaluate the relationship between repetitive concussion, local cerebral glucose metabolism, and brain temperature using the Marmarou weight drop model to generate mTBI. Animals were injured three consecutive times over a period of 7 days while exposed to either normothermic or hyperthermic temperatures for 15 min prior to and 1 h post each injury. A 14C-2-deoxy-d-glucose (2DG) autoradiography was used to measure local cerebral metabolic rate of glucose (lCMRGlc) in 10 diverse brain regions across nine bregma levels 8 days after the initial insult. We found that repetitive mTBI significantly decreased glucose utilization bilaterally in several cortical areas, such as the cingulate, visual, motor, and retrosplenial cortices, as well as in subcortical areas, including the caudate putamen and striatum, compared to sham control animals. lCMRGlc was significant in both normothermic and hyperthermic repetitive mTBI animals relative to the sham group, but to a greater degree when exposed to hyperthermic conditions. Taken together, we report significant injury-induced glucose hypometabolism after repetitive concussion in the brain, and additionally highlight the importance of temperature management in the acute period after brain injury.

Dataset Information

A new mild hyperthermia device to treat vascular involvement in cancer surgery.

Publications

A new mild hyperthermia device to treat vascular involvement in cancer surgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets