Optimal temperature control of tissue embedded with gold nanoparticles for enhanced thermal therapy based on two-energy equation model.

PubMed

Wang, Shen-Ling; Qi, Hong; Ren, Ya-Tao; Chen, Qin; Ruan, Li-Ming

2018-05-01

Thermal therapy is a very promising method for cancer treatment, which can be combined with chemotherapy, radiotherapy and other programs for enhanced cancer treatment. In order to get a better effect of thermal therapy in clinical applications, optimal internal temperature distribution of the tissue embedded with gold nanoparticles (GNPs) for enhanced thermal therapy was investigated in present research. The Monte Carlo method was applied to calculate the heat generation of the tissue embedded with GNPs irradiated by continuous laser. To have a better insight into the physical problem of heat transfer in tissues, the two-energy equation was employed to calculate the temperature distribution of the tissue in the process of GNPs enhanced therapy. The Arrhenius equation was applied to evaluate the degree of permanent thermal damage. A parametric study was performed to investigate the influence factors on the tissue internal temperature distribution, such as incident light intensity, the GNPs volume fraction, the periodic heating and cooling time, and the incident light position. It was found that period heating and cooling strategy can effectively avoid overheating of skin surface and heat damage of healthy tissue. Lower GNPs volume fraction will be better for the heat source distribution. Furthermore, the ring heating strategy is superior to the central heating strategy in the treatment effect. All the analysis provides theoretical guidance for optimal temperature control of tissue embedded with GNP for enhanced thermal therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improvement in skin elasticity in the treatment of cellulite and connective tissue weakness by means of extracorporeal pulse activation therapy.

PubMed

Christ, Christophe; Brenke, Rainer; Sattler, Gerhard; Siems, Werner; Novak, Pavel; Daser, A

2008-01-01

Extracorporeal pulse activation therapy (EPAT), also called extracorporeal acoustic wave therapy, seeks to achieve effective and long-lasting improvement of age-related connective tissue weakness in the extremities, especially in the treatment of unsightly cosmetic skin defects referred to as cellulite. The objective of this study was to stimulate metabolic activity in subcutaneous fat tissue by means of EPAT in order evaluate its effectiveness in enhancing connective tissue firmness and improving skin texture and structure. Fifty-nine women with advanced cellulite were divided into 2 groups; one group of 15 patients received planar acoustic wave treatment for 6 therapy sessions within 3 weeks; a second group of 44 patients received 8 therapy sessions within 4 weeks. Changes in connective tissue were evaluated using the DermaScan C ultrasound system (Cortex Technology, Hadsund, Denmark). Skin elasticity measurements were performed using the DermaLab system (Cortex Technology). Photographs of treated areas were taken at each therapy session and at follow-up sessions. Skin elasticity values gradually improved over the course of EPAT therapy and revealed a 73% increase at the end of therapy. At 3- and 6-month follow-ups, skin elasticity had even improved by 95% and 105%, respectively. Side effects included minor pain for 3 patients during therapy and slight skin reddening. This study confirmed the effects of acoustic wave therapy on biologic tissue, including stimulation of microcirculation and improvement of cell permeability. Ultrasound evaluation demonstrated increased density and firmness in the network of collagen/elastic fibers in the dermis and subcutis. Treatment was most effective in older patients with a long history of cellulite.

A practical model for economic evaluation of tissue-engineered therapies.

PubMed

Tan, Tien-En; Peh, Gary S L; Finkelstein, Eric A; Mehta, Jodhbir S

2015-01-01

Tissue-engineered therapies are being developed across virtually all fields of medicine. Some of these therapies are already in clinical use, while others are still in clinical trials or the experimental phase. Most initial studies in the evaluation of new therapies focus on demonstration of clinical efficacy. However, cost considerations or economic viability are just as important. Many tissue-engineered therapies have failed to be impactful because of shortcomings in economic competitiveness, rather than clinical efficacy. Furthermore, such economic viability studies should be performed early in the process of development, before significant investment has been made. Cost-minimization analysis combined with sensitivity analysis is a useful model for the economic evaluation of new tissue-engineered therapies. The analysis can be performed early in the development process, and can provide valuable information to guide further investment and research. The utility of the model is illustrated with the practical real-world example of tissue-engineered constructs for corneal endothelial transplantation. The authors have declared no conflicts of interest for this article. © 2015 Wiley Periodicals, Inc.

Design control for clinical translation of 3D printed modular scaffolds.

PubMed

Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion.

Design Control for Clinical Translation of 3D Printed Modular Scaffolds

PubMed Central

Hollister, Scott J.; Flanagan, Colleen L.; Zopf, David A.; Morrison, Robert J.; Nasser, Hassan; Patel, Janki J.; Ebramzadeh, Edward; Sangiorgio, Sophia N.; Wheeler, Matthew B.; Green, Glenn E.

2015-01-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion. PMID:25666115

Childhood Soft Tissue Sarcoma Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood soft tissue sarcoma treatment options include surgery, radiation therapy, chemotherapy, observation, targeted therapy, immunotherapy and other medications.  Learn more about the diagnosis and treatment of the many types of childhood soft tissue sarcoma in this expert-reviewed summary.

Periodontal and peri-implant wound healing following laser therapy.

PubMed

Aoki, Akira; Mizutani, Koji; Schwarz, Frank; Sculean, Anton; Yukna, Raymond A; Takasaki, Aristeo A; Romanos, Georgios E; Taniguchi, Yoichi; Sasaki, Katia M; Zeredo, Jorge L; Koshy, Geena; Coluzzi, Donald J; White, Joel M; Abiko, Yoshimitsu; Ishikawa, Isao; Izumi, Yuichi

2015-06-01

Laser irradiation has numerous favorable characteristics, such as ablation or vaporization, hemostasis, biostimulation (photobiomodulation) and microbial inhibition and destruction, which induce various beneficial therapeutic effects and biological responses. Therefore, the use of lasers is considered effective and suitable for treating a variety of inflammatory and infectious oral conditions. The CO2 , neodymium-doped yttrium-aluminium-garnet (Nd:YAG) and diode lasers have mainly been used for periodontal soft-tissue management. With development of the erbium-doped yttrium-aluminium-garnet (Er:YAG) and erbium, chromium-doped yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers, which can be applied not only on soft tissues but also on dental hard tissues, the application of lasers dramatically expanded from periodontal soft-tissue management to hard-tissue treatment. Currently, various periodontal tissues (such as gingiva, tooth roots and bone tissue), as well as titanium implant surfaces, can be treated with lasers, and a variety of dental laser systems are being employed for the management of periodontal and peri-implant diseases. In periodontics, mechanical therapy has conventionally been the mainstream of treatment; however, complete bacterial eradication and/or optimal wound healing may not be necessarily achieved with conventional mechanical therapy alone. Consequently, in addition to chemotherapy consisting of antibiotics and anti-inflammatory agents, phototherapy using lasers and light-emitting diodes has been gradually integrated with mechanical therapy to enhance subsequent wound healing by achieving thorough debridement, decontamination and tissue stimulation. With increasing evidence of benefits, therapies with low- and high-level lasers play an important role in wound healing/tissue regeneration in the treatment of periodontal and peri-implant diseases. This article discusses the outcomes of laser therapy in soft-tissue management, periodontal nonsurgical and surgical treatment, osseous surgery and peri-implant treatment, focusing on postoperative wound healing of periodontal and peri-implant tissues, based on scientific evidence from currently available basic and clinical studies, as well as on case reports. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Maggot therapy for gangrene and osteomyelitis].

PubMed

Mumcuoglu, K Y; Lipo, M; Ioffe-Uspensky, I; Miller, J; Galun, R

1997-03-02

5 patients with diabetic-foot were treated by maggot therapy. The most serious case was in a 75-year-old man who had gangrene and osteomyelitis of the right foot. Proteus mirabilis, Enterococcus sp., Providencia stuartii and Staphylococcus spec. (coagulase positive) were isolated from lesions which did not respond to antibiotic therapy. The patient had twice refused amputation but agreed to maggot therapy. Larvae of the sheep blowfly Phoenicia (Lucilia) sericata were used for twice-weekly treatment over a period of 7 months. Sterile larvae were applied to the wound and replaced every 3-4 days. After 4 months of treatment, the necrotic tissue around the toes and on the sole of the foot detached from the healthy tissue. During the last 3 months of treatment the larvae removed the remaining infected tissue. As therapy progressed, new layers of healthy tissue covered the wound. The offensive odor associated with the necrotic tissue and the intense pain in the foot decreased significantly. At the end of therapy, during which there were no complaints of discomfort, he was able to walk. In the 4 other patients who had relatively superficial gangrene, the maggots debrided the wounds within 2-4 weeks. Thereafter treatment was continued with antibiotics. Maggot therapy can be recommended in cases of intractable gangrene and osteomyelitis, when treatment with antibiotics and surgical debridement have failed.

Legal basis of the Advanced Therapies Regulation.

PubMed

Jekerle, V; Schröder, C; Pedone, E

2010-01-01

Advanced therapy medicinal products consist of gene therapy, somatic cell therapy and tissue engineered products. Due to their specific manufacturing process and mode of action these products require specially tailored legislation. With Regulation (EC) No. 1394/2007, these needs have been met. Definitions of gene therapy, somatic cell therapy and tissue engineered products were laid down. A new committee, the Committee for Advanced Therapies, was founded, special procedures such as the certification procedure for small- and medium-sized enterprises were established and the technical requirements for Marketing Authorisation Applications (quality, non-clinical and clinical) were revised.

Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.

PubMed

Jansen, H J; Stienstra, R; van Diepen, J A; Hijmans, A; van der Laak, J A; Vervoort, G M M; Tack, C J

2013-12-01

Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight. We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status. ClinicalTrials.gov: NCT00781495. The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.

A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration.

PubMed

MacIsaac, Rachael L; Khatri, Pooja; Bendszus, Martin; Bracard, Serge; Broderick, Joseph; Campbell, Bruce; Ciccone, Alfonso; Dávalos, Antoni; Davis, Stephen M; Demchuk, Andrew; Diener, Hans-Christoph; Dippel, Diederik; Donnan, Geoffrey A; Fiehler, Jens; Fiorella, David; Goyal, Mayank; Hacke, Werner; Hill, Michael D; Jahan, Reza; Jauch, Edward; Jovin, Tudor; Kidwell, Chelsea S; Liebeskind, David; Majoie, Charles B; Martins, Sheila Cristina Ouriques; Mitchell, Peter; Mocco, J; Muir, Keith W; Nogueira, Raul; Saver, Jeffrey L; Schonewille, Wouter J; Siddiqui, Adnan H; Thomalla, Götz; Tomsick, Thomas A; Turk, Aquilla S; White, Philip; Zaidat, Osama; Lees, Kennedy R

2015-10-01

Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow. This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication. © 2015 World Stroke Organization.

Thermal therapy techniques for skin and superficial tissue disease

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.

2000-01-01

There are numerous diseases and abnormal growths and conditions that afflict the skin and underlying superficial tissues. In addition to cancers such as primary, recurrent, and metastatic melanomas and carcinomas, there are many non-malignant conditions such as psoriasis plaques, port wine stains, warts, and superficial cut and bum wounds. Many of these clinical conditions have been shown responsive to treatment with thermal therapy - either low temperature freezing (cryotherapy),. moderate temperature warming to about 41-45°C (hyperthermia), or high temperature (>50°C) ablation or coagulation necrosis therapy. Because both very low and very high temperature therapies are for the most part non-selectively destructive in nature, they normally are used for applications where therapy can be localized precisely in the desired target and some necrosis of adjacent normal tissues is acceptable. With the exception of precision controlled cryotherapy or laser surgery (e.g. wart, mole, tattoo and port wine stain removal) or focal thermal surgery of small deep-seated nodules, it is generally preferred to use moderate thermal therapy (hyperthermia) in the treatment of skin and subcutaneous tissue disease in order to preserve the protective barrier characteristic of intact skin within the target region while inducing more subtle long term therapeutic improvement in the disease condition. This type of subtle thermal therapy is usually administered in combination with one or more other therapies such as radiation or chemotherapy - something with a differential effect on the target and surrounding normal tissues that can be magnified by the adjuvant use of heat.

Pilot study: whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with lipedema.

PubMed

Herbst, Karen L; Ussery, Christopher; Eekema, Alyna

2017-09-20

Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

An innovative therapy for peri-implantitis based on radio frequency electric current: numerical simulation results and clinical evidence.

PubMed

Cosoli, G; Scalise, L; Tricarico, G; Tomasini, E P; Cerri, G

2016-08-01

Peri-implantitis is a severe inflammatory pathology that affects soit and hard tissues surrounding dental implants. Nowadays, only prevention is effective to contrast peri-implantitis, but, in recent years, there is the clinical evidence of the efficiency of a therapy based on the application of radio frequency electric current, reporting that 81% of the cases (66 implants, 46 patients) were successfully treated. The aim of this paper is to present the therapy mechanism, exploring the distribution of the electric currents in normal and pathologic tissues. A 3D numerical FEM model of tooth root with a dental implant screwed in the alveolar bone has been realized and the therapy has been simulated in COMSOL Multiphysics® environment. Results show that the electric current is focused in the inflamed zone around the implant, due to the fact that its conductivity is higher than the healthy tissue one. Moreover, by means of a movable return electrode, the electric current and field lines can be guided in the most inflamed area, limiting the interference on healthy tissues and improving the therapy in the area of interest. In conclusion, it can be stated that this innovative therapy would make a personalized therapy for peri-implantitis possible, also through impedance measurements, allowing the clinician to evaluate the tissue inflammation state.

Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

NASA Astrophysics Data System (ADS)

Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

2017-05-01

Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

Cell delivery in regenerative medicine: the cell sheet engineering approach.

PubMed

Yang, Joseph; Yamato, Masayuki; Nishida, Kohji; Ohki, Takeshi; Kanzaki, Masato; Sekine, Hidekazu; Shimizu, Tatsuya; Okano, Teruo

2006-11-28

Recently, cell-based therapies have developed as a foundation for regenerative medicine. General approaches for cell delivery have thus far involved the use of direct injection of single cell suspensions into the target tissues. Additionally, tissue engineering with the general paradigm of seeding cells into biodegradable scaffolds has also evolved as a method for the reconstruction of various tissues and organs. With success in clinical trials, regenerative therapies using these approaches have therefore garnered significant interest and attention. As a novel alternative, we have developed cell sheet engineering using temperature-responsive culture dishes, which allows for the non-invasive harvest of cultured cells as intact sheets along with their deposited extracellular matrix. Using this approach, cell sheets can be directly transplanted to host tissues without the use of scaffolding or carrier materials, or used to create in vitro tissue constructs via the layering of individual cell sheets. In addition to simple transplantation, cell sheet engineered constructs have also been applied for alternative therapies such as endoscopic transplantation, combinatorial tissue reconstruction, and polysurgery to overcome limitations of regenerative therapies and cell delivery using conventional approaches.

Minibeam therapy with protons and light ions: physical feasibility and potential to reduce radiation side effects and to facilitate hypofractionation.

PubMed

Dilmanian, F Avraham; Eley, John G; Krishnan, Sunil

2015-06-01

Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulations were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of photodynamic laser therapy in the treatment of marginal chronic periodontitis

NASA Astrophysics Data System (ADS)

Chifor, Radu; Badea, Iulia; Avram, Ramona; Chifor, Ioana; Badea, Mîndra Eugenia

2016-03-01

The aim of this study was to assess the effects of the antimicrobial photodynamic laser therapy performed during the treatment of deep periodontal disease by using 40 MHz high frequency ultrasonography. The periodontal data recorded during the clinical examination before each treatment session were compared with volumetric changes of the gingiva measured on periodontal ultrasound images. The results show a significant decrease of gingival tissue inflammation proved both by a significant decrease of bleeding on probing as well as by a decrease of the gingival tissues volume on sites where the laser therapy was performed. Periodontal tissues that benefit of laser therapy besides classical non-surgical treatment showed a significant clinical improvement of periodontal status. Based on these findings we were able to conclude that the antimicrobial photodynamic laser therapy applied on marginal periodontium has important anti-inflamatory effect. The periodontal ultrasonography is a method which can provide useful data for assessing the volume changes of gingival tissues, allowing a precise monitoring of marginal periodontitis.

Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

PubMed

Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

2017-09-01

Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Redox-Modulated Phenomena and Radiation Therapy: The Central Role of Superoxide Dismutases

PubMed Central

Holley, Aaron K.; Miao, Lu; St. Clair, Daret K.

2014-01-01

Abstract Significance: Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged directly by radiation or indirectly through reactive oxygen species (ROS) formed from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting from altered aerobic metabolism. Recent Advances: ROS are produced as a byproduct of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers. ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs modulate the radioresponsiveness of tissues, thus affecting the efficacy of radiotherapy. Critical Issues: Despite its prevalent use, radiation therapy suffers from certain limitations that diminish its effectiveness, including tumor hypoxia and normal tissue damage. Oxygen is important for the stabilization of radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness of radiation therapy against tumor tissues while minimizing normal tissue injury. Future Directions: Because of the importance of ROS in the response of normal and cancer tissues to ionizing radiation, methods that differentially modulate the ROS scavenging ability of cells may prove to be an important method to increase the radiation response in cancer tissues and simultaneously mitigate the damaging effects of ionizing radiation on normal tissues. Altering the expression or activity of SODs may prove valuable in maximizing the overall effectiveness of ionizing radiation. Antioxid. Redox Signal. 20, 1567–1589. PMID:24094070

Expediting the transition from replacement medicine to tissue engineering.

PubMed

Coury, Arthur J

2016-06-01

In this article, an expansive interpretation of "Tissue Engineering" is proposed which is in congruence with classical and recent published definitions. I further simplify the definition of tissue engineering as: "Exerting systematic control of the body's cells, matrices and fluids." As a consequence, many medical therapies not commonly considered tissue engineering are placed in this category because of their effect on the body's responses. While the progress of tissue engineering strategies is inexorable and generally positive, it has been subject to setbacks as have many important medical therapies. Medical practice is currently undergoing a transition on several fronts (academics, start-up companies, going concerns) from the era of "replacement medicine" where body parts and functions are replaced by mechanical, electrical or chemical therapies to the era of tissue engineering where health is restored by regeneration generation or limitation of the body's tissues and functions by exploiting our expanding knowledge of the body's biological processes to produce natural, healthy outcomes.

Systemic sclerosis-scleroderma.

PubMed

Haustein, U-F

2002-06-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.

21 CFR 5.1100 - Headquarters.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Laboratories Complex Staff. Division of Engineering Services. Environment, Safety And Strategic Initiatives.... Office of Cellular, Tissue, and Gene Therapies. Regulatory Management Staff. Division of Cellular and Gene Therapies. Division of Clinical Evaluation and Pharmacology/Toxicology. Division of Human Tissues...

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

NASA Astrophysics Data System (ADS)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

PubMed

Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

2016-03-01

The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

Regenerative endodontics as a tissue engineering approach: past, current and future.

PubMed

Malhotra, Neeraj; Mala, Kundabala

2012-12-01

With the reported startling statistics of high incidence of tooth decay and tooth loss, the current interest is focused on the development of alternate dental tissue replacement therapies. This has led to the application of dental tissue engineering as a clinically relevant method for the regeneration of dental tissues and generation of bioengineered whole tooth. Although, tissue engineering approach requires the three main key elements of stem cells, scaffold and morphogens, a conductive environment (fourth element) is equally important for successful engineering of any tissue and/or organ. The applications of this science has evolved continuously in dentistry, beginning from the application of Ca(OH)(2) in vital pulp therapy to the development of a fully functional bioengineered tooth (mice). Thus, with advances in basic research, recent reports and studies have shown successful application of tissue engineering in the field of dentistry. However, certain practical obstacles are yet to be overcome before dental tissue regeneration can be applied as evidence-based approach in clinics. The article highlights on the past achievements, current developments and future prospects of tissue engineering and regenerative therapy in the field of endodontics and bioengineered teeth (bioteeth). © 2012 The Authors. Australian Endodontic Journal © 2012 Australian Society of Endodontology.

[Radiation therapy and redox imaging].

PubMed

Matsumoto, Ken-ichiro

2015-01-01

Radiation therapy kills cancer cells in part by flood of free radicals. Radiation ionizes and/or excites water molecules to create highly reactive species, i.e. free radicals and/or reactive oxygen species. Free radical chain reactions oxidize biologically important molecules and thereby disrupt their function. Tissue oxygen and/or redox status, which can influence the course of the free radical chain reaction, can affect the efficacy of radiation therapy. Prior observation of tissue oxygen and/or redox status is helpful for planning a safe and efficient course of radiation therapy. Magnetic resonance-based redox imaging techniques, which can estimate tissue redox status non-invasively, have been developed not only for diagnostic information but also for estimating the efficacy of treatment. Redox imaging is now spotlighted to achieve radiation theranostics.

A Dosimetric Comparison of Proton and Intensity-Modulated Photon Radiotherapy for Pediatric Parameningeal Rhabdomyosarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less

Two complementary strategies to improve cell engraftment in mesenchymal stem cell-based therapy: Increasing transplanted cell resistance and increasing tissue receptivity.

PubMed

Ezquer, Fernando E; Ezquer, Marcelo E; Vicencio, Jose M; Calligaris, Sebastián D

2017-01-02

Over the past 2 decades, therapies based on mesenchymal stem cells (MSC) have been tested to treat several types of diseases in clinical studies, due to their potential for tissue repair and regeneration. Currently, MSC-based therapy is considered a biologically safe procedure, with the therapeutic results being very promising. However, the benefits of these therapies are not stable in the long term, and the final outcomes manifest with high inter-patient variability. The major cause of these therapeutic limitations results from the poor engraftment of the transplanted cells. Researchers have developed separate strategies to improve MSC engraftment. One strategy aims at increasing the survival of the transplanted MSCs in the recipient tissue, rendering them more resistant to the hostile microenvironment (cell-preconditioning). Another strategy aims at making the damaged tissue more receptive to the transplanted cells, favoring their interactions (tissue-preconditioning). In this review, we summarize several approaches using these strategies, providing an integral and updated view of the recent developments in MSC-based therapies. In addition, we propose that the combined use of these different conditioning strategies could accelerate the process to translate experimental evidences from pre-clinic studies to the daily clinical practice.

Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant".

PubMed

Raik, Shalini; Kumar, Ajay; Bhattacharyya, Shalmoli

2018-03-01

Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Minibeam Therapy With Protons and Light Ions: Physical Feasibility and Potential to Reduce Radiation Side Effects and to Facilitate Hypofractionation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilmanian, F. Avraham, E-mail: avraham.dilmanian@stonybrook.edu; Eley, John G.; Krishnan, Sunil

2015-06-01

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Methods and Materials: Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulationsmore » were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. Results: A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Conclusions: Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage.« less

The clinical use of regenerative therapy in COPD

PubMed Central

Lipsi, Roberto; Rogliani, Paola; Calzetta, Luigino; Segreti, Andrea; Cazzola, Mario

2014-01-01

Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. PMID:25548520

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy

PubMed Central

Hipp, Jason; Atala, Anthony

2004-01-01

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. PMID:15588286

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy.

PubMed

Hipp, Jason; Atala, Anthony

2004-12-08

: BACKGROUND: Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

Nano scaffolds and stem cell therapy in liver tissue engineering

NASA Astrophysics Data System (ADS)

Montaser, Laila M.; Fawzy, Sherin M.

2015-08-01

Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

Predicted coreceptor usage at end-stage HIV disease in tissues derived from subjects on antiretroviral therapy with an undetectable plasma viral load.

PubMed

Lamers, S L; Fogel, G B; Liu, E S; Nolan, D J; Salemi, M; Barbier, A E; Rose, R; Singer, E J; McGrath, M S

2017-07-01

HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy. In this study, we pooled 1806 HIV envelope V3 loop sequences from twenty-six tissue types (seventy-one total tissues) of six pre-cART subjects, four subjects with an unknown cART history who died with profound AIDS, and five subjects who died while on cART with an undetectable plasma viral load. A computational approach was used to assess sequences for their ability to utilize specific cellular coreceptors (R5, R5 and X4, or X4). We found that autopsied tissues obtained from virally suppressed cART+ subjects harbored both integrated and expressed viruses with similar coreceptor usage profiles to subjects with no or ineffective cART therapy (i.e., significant plasma viral load at death). The study suggests that tissue microenvironments provide a sanctuary for the continued evolution of HIV despite cART. Copyright © 2017 Elsevier B.V. All rights reserved.

Negative pressure wound therapy for the treatment of infected wounds with exposed knee joint after patellar fracture.

PubMed

Lee, Sang Yang; Niikura, Takahiro; Miwa, Masahiko; Sakai, Yoshitada; Oe, Keisuke; Fukazawa, Takahiro; Kawakami, Yohei; Kurosaka, Masahiro

2011-06-14

Treatment of soft tissue defects with exposed bones and joints, resulting from trauma, infection, and surgical complications, represents a major challenge. The introduction of negative pressure wound therapy has changed many wound management practices. Negative pressure wound therapy has recently been used in the orthopedic field for management of traumatic or open wounds with exposed bone, nerve, tendon, and orthopedic implants. This article describes a case of a patient with a large soft tissue defect and exposed knee joint, in which negative pressure wound therapy markedly improved wound healing. A 50-year-old man presented with an ulceration of his left knee with exposed joint, caused by severe wound infections after open reduction and internal fixation of a patellar fracture. After 20 days of negative pressure wound therapy, a granulated wound bed covered the exposed bones and joint.To our knowledge, this is the first report of negative pressure wound therapy used in a patient with a large soft tissue defect with exposed knee joint. Despite the chronic wound secondary to infection, healing was achieved through the use of the negative pressure wound therapy, thus promoting granulation tissue formation and closing the joint. We suggest negative pressure wound therapy as an alternative option for patients with lower limb wounds containing exposed bones and joints when free flap transfer is contraindicated. Our result added to the growing evidence that negative pressure wound therapy is a useful adjunctive treatment for open wounds around the knee joint. Copyright 2011, SLACK Incorporated.

Method for estimating optimal spectral and energy parameters of laser irradiation in photodynamic therapy of biological tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lisenko, S A; Kugeiko, M M

We have solved the problem of layer-by-layer laser-light dosimetry in biological tissues and of selecting an individual therapeutic dose in laser therapy. A method is proposed for real-time monitoring of the radiation density in tissue layers in vivo, concentrations of its endogenous (natural) and exogenous (specially administered) chromophores, as well as in-depth distributions of the spectrum of light action on these chromophores. As the background information use is made of the spectrum of diffuse light reflected from a patient's tissue, measured by a fibre-optic spectrophotometer. The measured spectrum is quantitatively analysed by the method of approximating functions for fluxes ofmore » light multiply scattered in tissue and by a semi-analytical method for calculating the in-depth distribution of the light flux in a multi-layered medium. We have shown the possibility of employing the developed method for monitoring photosensitizer and oxyhaemoglobin concentrations in tissue, light power absorbed by chromophores in tissue layers at different depths and laser-induced changes in the tissue morphology (vascular volume content and ratios of various forms of haemoglobin) during photodynamic therapy. (biophotonics)« less

Solid Free-form Fabrication Technology and Its Application to Bone Tissue Engineering

PubMed Central

Lee, Jin Woo; Kim, Jong Young; Cho, Dong-Woo

2010-01-01

The development of scaffolds for use in cell-based therapies to repair damaged bone tissue has become a critical component in the field of bone tissue engineering. However, design of scaffolds using conventional fabrication techniques has limited further advancement, due to a lack of the required precision and reproducibility. To overcome these constraints, bone tissue engineers have focused on solid free-form fabrication (SFF) techniques to generate porous, fully interconnected scaffolds for bone tissue engineering applications. This paper reviews the potential application of SFF fabrication technologies for bone tissue engineering with respect to scaffold fabrication. In the near future, bone scaffolds made using SFF apparatus should become effective therapies for bone defects. PMID:24855546

Reduction of thermal damage in photodynamic therapy by laser irradiation techniques.

PubMed

Lim, Hyun Soo

2012-12-01

General application of continuous-wave (CW) laser irradiation modes in photodynamic therapy can cause thermal damage to normal tissues in addition to tumors. A new photodynamic laser therapy system using a pulse irradiation mode was optimized to reduce nonspecific thermal damage. In in vitro tissue specimens, tissue energy deposition rates were measured in three irradiation modes, CW, pulse, and burst-pulse. In addition, methods were tested for reducing variations in laser output and specific wavelength shifts using a thermoelectric cooler and thermistor. The average temperature elevation per 10 J/cm2 was 0.27°C, 0.09°C, and 0.08°C using the three methods, respectively, in pig muscle tissue. Variations in laser output were controlled within ± 0.2%, and specific wavelength shift was limited to ± 3 nm. Thus, optimization of a photodynamic laser system was achieved using a new pulse irradiation mode and controlled laser output to reduce potential thermal damage during conventional CW-based photodynamic therapy.

Maggot therapy in treatment of a complex hand injury complicated by mycotic infection.

PubMed

Bohac, M; Cambal, M; Zamborsky, R; Takac, P; Fedeles, J

2015-01-01

Complex injuries of the hand remain a therapeutic challenge for surgeons. We present the case of a male who suffered a devastating injury of the hand caused by a conveyor belt. The patient developed a progressive Absidia corymbifera infection of the affected soft tissues. Initial treatments with serial surgical debridement and topical and intravenous itraconazole were unsuccessful in eliminating the infection. We decided to use maggot debridement therapy in a new special design to debride all necrotic, devitalized tissue and preserve only healthy tissue and functioning structures. This maneuverer followed by negative pressure therapy allowed progressive healing. In such complex hand injuries, maggot debridement combined with negative pressure therapy could be considered to achieve effective and considerable results, although future functional morbidity may occur (Fig. 4, Ref. 18).

SU-D-BRC-04: Development of Proton Tissue Equivalent Materials for Calibration and Dosimetry Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olguin, E; Flampouri, S; Lipnharski, I

Purpose: To develop new proton tissue equivalent materials (PTEM), urethane and fiberglass based, for proton therapy calibration and dosimetry studies. Existing tissue equivalent plastics are applicable only for x-rays because they focus on matching mass attenuation coefficients. This study aims to create new plastics that match mass stopping powers for proton therapy applications instead. Methods: New PTEMs were constructed using urethane and fiberglass resin materials for soft, fat, bone, and lung tissue. The stoichiometric analysis method was first used to determine the elemental composition of each unknown constituent. New initial formulae were then developed for each of the 4 PTEMsmore » using the new elemental compositions and various additives. Samples of each plastic were then created and exposed to a well defined proton beam at the UF Health Proton Therapy Institute (UFHPTI) to validate its mass stopping power. Results: The stoichiometric analysis method revealed the elemental composition of the 3 components used in creating the PTEMs. These urethane and fiberglass based resins were combined with additives such as calcium carbonate, aluminum hydroxide, and phenolic micro spheres to achieve the desired mass stopping powers and densities. Validation at the UFHPTI revealed adjustments had to be made to the formulae, but the plastics eventually had the desired properties after a few iterations. The mass stopping power, density, and Hounsfield Unit of each of the 4 PTEMs were within acceptable tolerances. Conclusion: Four proton tissue equivalent plastics were developed: soft, fat, bone, and lung tissue. These plastics match each of the corresponding tissue’s mass stopping power, density, and Hounsfield Unit, meaning they are truly tissue equivalent for proton therapy applications. They can now be used to calibrate proton therapy treatment planning systems, improve range uncertainties, validate proton therapy Monte Carlo simulations, and assess in-field and out-of-field organ doses.« less

Cancer Nanotechnology: Opportunities for Prevention, Diagnosis, and Therapy.

PubMed

Zeineldin, Reema; Syoufjy, Joan

2017-01-01

Nanotechnological innovations over the last 16 years have brought about the potential to revolutionize specific therapeutic drug delivery to cancer tissue without affecting normal tissues. In addition, there are new nanotechnology-based platforms for diagnosis of cancers and for theranostics, i.e., integrating diagnosis with therapy and follow-up of effectiveness of therapy. This chapter presents an overview of these nanotechnology-based advancements in the areas of prevention, diagnosis, therapy, and theranostics for cancer. In addition, we stress the need to educate bio- and medical students in the field of nanotechnology.

New Approaches in Vital Pulp Therapy in Permanent Teeth

PubMed Central

Ghoddusi, Jamileh; Forghani, Maryam; Parisay, Iman

2014-01-01

Vitality of dental pulp is essential for long-term tooth survival. The aim of vital pulp therapy is to maintain healthy pulp tissue by eliminating bacteria from the dentin-pulp complex. There are several different treatment options for vital pulp therapy in extensively decayed or traumatized teeth. Pulp capping or pulpotomy procedures rely upon an accurate assessment of the pulp status, and careful management of the remaining pulp tissue. The purpose of this review is to provide an overview of new approaches in vital pulp therapy in permanent teeth. PMID:24396371

Current and future regenerative medicine — Principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

PubMed Central

Koch, Thomas G.; Berg, Lise C.; Betts, Dean H.

2009-01-01

This paper provides a bird’s-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine. The understanding of equine stem cell biology, biofactors, and scaffolds, and their potential therapeutic use in horses are rudimentary at present. Mesenchymal stem cell isolation has been proclaimed from several equine tissues in the past few years. Based on the criteria of the International Society for Cellular Therapy, most of these cells are more correctly referred to as multipotent mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering — cells, biological factors, and biomaterials — are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources. The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently in controlled clinical trials in equine patients to be regarded as evidence-based medicine. In the meantime, the medical mantra “do no harm” should prevail, and the application of stem cell-based therapies in the horse should be done critically and cautiously, and treatment outcomes (good and bad) should be recorded and reported. Stem cell and tissue engineering research in the horse has exciting comparative and equine specific perspectives that most likely will benefit the health of horses and humans. Controlled, well-designed studies are needed to move this new equine research field forward. PMID:19412395

Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)

PubMed Central

Gao, Wenqing; Dalton, James T.

2007-01-01

Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contributions of differential tissue distribution, tissue-specific expression of 5α-reductase, ligand-specific regulation of gene expression and AR interactions with tissue-specific coactivators to their observed tissue selectivity, and lead to even greater expansion of selective anabolic therapies. PMID:17331889

Nonpharmaceutical approaches to pain management.

PubMed

Corti, Lisa

2014-03-01

A nonpharmaceutical approach to managing pain is one that does not employ a medication. The use of such approaches, in conjunction with pharmaceuticals as part of multimodal methods to managing pain, is becoming more popular as evidence is emerging to support their use. Cold therapy, for one, is used to reduce the inflammation and tissue damage seen in acute injuries and can be very effective at reducing acute pain. Incorporating the use of superficial heat therapy when treating pain associated with chronic musculoskeletal conditions is often employed as heat increases blood flow, oxygen delivery, and tissue extensibility. Acupuncture is gaining acceptance in veterinary medicine. Research is confirming that release of endogenous endorphins and enkephalins from the application of needles at specific points around the body can effectively control acute and chronic pain. The use of 2 newer therapies-extracorporeal shockwave therapy and platelet-rich plasma-represent an attempt to eliminate the causes of pain at the tissue level by promoting tissue healing and regeneration. Reviewed in this article, these therapies are intended to be used in conjunction with pharmaceuticals as part of a multimodal approach to pain management. Copyright © 2014 Elsevier Inc. All rights reserved.

Resectable Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma: Which Patients Benefit from Adjuvant Radiation Therapy and How Much?

PubMed Central

Million, Lynn; Donaldson, Sarah S.

2012-01-01

It remains unclear which children and adolescents with resected nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) benefit from radiation therapy, as well as the optimal dose, volume, and timing of radiotherapy when used with primary surgical resection. This paper reviews the sparse literature from clinical trials and retrospective studies of resected pediatric NRSTS to discern local recurrence rates in relationship to the use of radiation therapy. PMID:22523704

Concise Review: Mind the Gap: Challenges in Characterizing and Quantifying Cell- and Tissue-Based Therapies for Clinical Translation

PubMed Central

Rayment, Erin A; Williams, David J

2010-01-01

There are many challenges associated with characterizing and quantifying cells for use in cell- and tissue-based therapies. From a regulatory perspective, these advanced treatments must not only be safe and effective but also be made by high-quality manufacturing processes that allow for on-time delivery of viable products. Although sterility assays can be adapted from conventional bioprocessing, cell- and tissue-based therapies require more stringent safety assessments, especially in relation to use of animal products, immune reaction, and potential instability due to extended culture times. Furthermore, cell manufacturers who plan to use human embryonic stem cells in their therapies need to be particularly stringent in their final purification steps, due to the unrestricted growth potential of these cells. This review summarizes the current issues in characterization and quantification for cell- and tissue-based therapies, dividing these challenges into the regulatory themes of safety, potency, and manufacturing quality. It outlines current assays in use, as well as highlights the limits of many of these product release tests. Mode of action is discussed, with particular reference to in vitro surrogate assays that can be used to provide information to correlate with proposed in vivo patient efficacy. Importantly, this review highlights the requirement for basic research to improve current knowledge on the in vivo fate of these treatments; as well as an improved stakeholder negotiation process to identify the measurement requirements that will ensure the manufacture of the best possible cell- and tissue-based therapies within the shortest timeframe for the most patient benefit. PMID:20333747

Time-Dependent Recovery of Human Synovial Membrane Mesenchymal Stem Cell Function After High-Dose Steroid Therapy: Case Report and Laboratory Study.

PubMed

Yasui, Yukihiko; Hart, David A; Sugita, Norihiko; Chijimatsu, Ryota; Koizumi, Kota; Ando, Wataru; Moriguchi, Yu; Shimomura, Kazunori; Myoui, Akira; Yoshikawa, Hideki; Nakamura, Norimasa

2018-03-01

The use of mesenchymal stem cells from various tissue sources to repair injured tissues has been explored over the past decade in large preclinical models and is now moving into the clinic. To report the case of a patient who exhibited compromised mesenchymal stem cell (MSC) function shortly after use of high-dose steroid to treat Bell's palsy, who recovered 7 weeks after therapy. Case report and controlled laboratory study. A patient enrolled in a first-in-human clinical trial for autologous implantation of a scaffold-free tissue engineered construct (TEC) derived from synovial MSCs for chondral lesion repair had a week of high-dose steroid therapy for Bell's palsy. Synovial tissue was harvested for MSC preparation after a 3-week recovery period and again at 7 weeks after therapy. The MSC proliferation rates and cell surface marker expression profiles from the 3-week sample met conditions for further processing. However, the cells failed to generate a functional TEC. In contrast, MSCs harvested at 7 weeks after steroid therapy were functional in this regard. Further in vitro studies with MSCs and steroids indicated that the effect of in vivo steroids was likely a direct effect of the drug on the MSCs. This case suggests that MSCs are transiently compromised after high-dose steroid therapy and that careful consideration regarding timing of MSC harvest is critical. The drug profiles of MSC donors and recipients must be carefully monitored to optimize opportunities to successfully repair damaged tissues.

In vivo neutron activation analysis of sodium and chlorine in tumor tissue after fast neutron therapy.

PubMed

Auberger, T; Koester, L; Knopf, K; Weissfloch, L

1996-01-01

In 12 patients with recurrences and metastases of different primaries (head and neck cancer, breast cancer, malignant melanoma, and osteosarcoma) who were treated with reactor fission neutrons the photon emission of irradiated tissue was measured after each radiotherapy fraction. Spectral analyses of the decay rates resulted in data for the exchange of sodium (Na) and chlorine (Cl) between the irradiated tissue and the body. About 60% of Na and Cl exchanged rapidly with a turnover half-life of 13 +/- 2 min. New defined mass exchange rates for Na and Cl amount to an average of 0.8 mval/min/kg of soft tissue. At the beginning of radiotherapy the turnover of the electrolytes in tissues with large tumor volumes was about twice that in tissues with small tumor volumes. Depending on the dose, neutron therapy led in all cases to variation in the metabolism. A maximum of Cl exchange and a minimum of Na exchange occurred after 10 Gy of neutrons (group of six previously untreated patients) or after 85 Gy (photon equivalent dose) of combined photon-neutron therapy. A significant increase in non-exchangeable fraction of Na from about 40 to 80% was observed in three tumors after a neutron dose of 10 Gy administered in five fractions correlated with a rapid reduction of tissue within 4 weeks after end of therapy. These results demonstrate for the first time the local response of the electrolyte metabolism to radiotherapy.

Pluripotent Stem Cells for Retinal Tissue Engineering: Current Status and Future Prospects.

PubMed

Singh, Ratnesh; Cuzzani, Oscar; Binette, François; Sternberg, Hal; West, Michael D; Nasonkin, Igor O

2018-04-19

The retina is a very fine and layered neural tissue, which vitally depends on the preservation of cells, structure, connectivity and vasculature to maintain vision. There is an urgent need to find technical and biological solutions to major challenges associated with functional replacement of retinal cells. The major unmet challenges include generating sufficient numbers of specific cell types, achieving functional integration of transplanted cells, especially photoreceptors, and surgical delivery of retinal cells or tissue without triggering immune responses, inflammation and/or remodeling. The advances of regenerative medicine enabled generation of three-dimensional tissues (organoids), partially recreating the anatomical structure, biological complexity and physiology of several tissues, which are important targets for stem cell replacement therapies. Derivation of retinal tissue in a dish creates new opportunities for cell replacement therapies of blindness and addresses the need to preserve retinal architecture to restore vision. Retinal cell therapies aimed at preserving and improving vision have achieved many improvements in the past ten years. Retinal organoid technologies provide a number of solutions to technical and biological challenges associated with functional replacement of retinal cells to achieve long-term vision restoration. Our review summarizes the progress in cell therapies of retina, with focus on human pluripotent stem cell-derived retinal tissue, and critically evaluates the potential of retinal organoid approaches to solve a major unmet clinical need-retinal repair and vision restoration in conditions caused by retinal degeneration and traumatic ocular injuries. We also analyze obstacles in commercialization of retinal organoid technology for clinical application.

Leech Therapy For The Treatment Of Venous Congestion In Flaps, Digital Re-Plants And Revascularizations - A Two-Year Review From A Regional Centre.

PubMed

Butt, Ahsan Masood; Ismail, Amir; Lawson-Smith, Matthew; Shahid, Muhammad; Webb, Jill; Chester, Darren L

2016-01-01

Leeches are a well-recognized treatment for congested tissue. This study reviewed the efficacy of leech therapy for salvage of venous congested flaps and congested replanted or revascularized hand digits over a 2-year period. All patients treated with leeches between 1 Oct 2010 and 30 Sep 2012 (two years) at Queen Elizabeth Hospital, Birmingham, UK were included in the study. Details regarding mode of injury requiring reconstruction, surgical procedure, leech therapy duration, subsequent surgery requirement and tissue salvage rates were recorded. Twenty tissues in 18 patients required leeches for tissue congestion over 2 years: 13 men and 5 women. The mean patient age was 41 years (range 17-79). The defect requiring reconstruction was trauma in 16 cases, following tumour resection in two, and two miscellaneous causes. Thirteen cases had flap reconstruction and seven digits in six patients had hand digit replantations or revascularisation. Thirteen of 20 cases (65%) had successful tissue salvage following leech therapy for congestion (77% in 10 out of 13 flaps, and 43% in 3 of 7 digits). The rate of tissue salvage in pedicled flaps was good 6/6 (100%) and so was in digital revascularizations 2/3 (67%), but poor in digital re-plants 1/4 (25%) and free flaps 0/2 (0%). Leeches are a helpful tool for congested tissue salvage and in this study, showed a greater survival benefit for pedicled flaps than for free flaps or digital replantations.

Does Proton Therapy Offer Demonstrable Clinical Advantages for Treating Thoracic Tumors?

PubMed

Liao, Zhongxing; Gandhi, Saumil J; Lin, Steven H; Bradley, Jeffrey

2018-04-01

The finite range of proton beams in tissues offers unique dosimetric advantages that theoretically allow dose to the target to be escalated while minimizing exposure of surrounding tissues and thus minimizing radiation-induced toxicity. This theoretical advantage has led to widespread adoption of proton therapy around the world for a wide variety of tumors at different anatomical sites. Many treatment-planning comparisons have shown that proton therapy has substantial dosimetric advantages over conventional radiotherapy. However, given the significant difference in cost for proton vs conventional photon therapy, thorough investigation of the evidence of proton therapy's clinical benefits in terms of toxicity and survival is warranted. Some data from retrospective studies, single-arm prospective studies, and a very few randomized clinical trials comparing these modalities are beginning to emerge. In this review, we examine the available data with regard to proton therapy for thoracic malignancies. We begin by discussing the unique challenges involved in treating moving targets with significant tissue heterogeneity and the technologic efforts underway to overcome these challenges. We then discuss the rationale for minimizing normal tissue toxicity, particularly pulmonary, cardiac, and hematologic toxicity, within the context of previously unsuccessful attempts at dose escalation for lung and esophageal cancer. Finally, we explore strategies for accelerating the development of trials aimed at measuring meaningful clinical endpoints and for maximizing the value of proton therapy by personalizing its use for individual patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Real-time three-dimensional temperature mapping in photothermal therapy with optoacoustic tomography

NASA Astrophysics Data System (ADS)

Oyaga Landa, Francisco Javier; Deán-Ben, Xosé Luís.; Sroka, Ronald; Razansky, Daniel

2017-07-01

Ablation and photothermal therapy are widely employed medical protocols where the selective destruction of tissue is a necessity as in cancerous tissue removal or vascular and brain abnormalities. Tissue denaturation takes place when the temperature reaches a threshold value while the time of exposure determines the lesion size. Therefore, the spatio-temporal distribution of temperature plays a crucial role in the outcome of these clinical interventions. We demonstrate fast volumetric temperature mapping with optoacoustic tomography based on real-time optoacoustic readings from the treated region. The performance of the method was investigated in tissue-mimicking phantom experiments. The new ability to non-invasively measure temperature volumetrically in an entire treated region with high spatial and temporal resolutions holds potential for improving safety and efficacy of thermal ablation and to advance the general applicability of laser-based therapy.

Clinical Application of Stem Cells in the Cardiovascular System

NASA Astrophysics Data System (ADS)

Stamm, Christof; Klose, Kristin; Choi, Yeong-Hoon

Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication of tissues and/or organs using scaffold material and viable cells - and "cell therapy" - the transplantation or manipulation of cells in diseased tissue in vivo. In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood vessels, heart valves, patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical applications of such vessels, valves and patches have been described, but information on systematic studies of the performance of such implants is not available, yet. Cell therapy for cardiovascular regeneration, however, has been performed in large series of patients, and numerous clinical studies have produced sometimes conflicting results. The purpose of this chapter is to summarize the clinical experience with cell therapy for diseases of the cardiovascular system, and to analyse possible factors that may influence its outcome.

Negative-pressure wound therapy and early pedicle flap reconstruction of the chest wall after epirubicin extravasation.

PubMed

Papadakis, Marios; Rahmanian-Schwarz, Afshin; Bednarek, Marzena; Arafkas, Mohamed; Holschneider, Philipp; Hübner, Gunnar

2017-05-15

Accidental extravasation is a serious iatrogenic injury among patients receiving anthracycline-containing chemotherapy. The aim of this work is to present a combination therapy for chest wall reconstruction following epirubicin extravasation. Herein, we report a 68-year-old woman with massive soft tissue necrosis of the anterolateral chest wall after epirubicin extravasation from a port implanted in the subclavicular area. The necrotic tissue was resected, the port was removed, and negative-pressure wound therapy was applied. Three weeks later, a latissimus dorsi pedicle flap was successfully used to cover the defect. To the best of the authors' knowledge, this is the first report of a strategy comprising the combination of negative-pressure wound therapy and a latissimus pedicle flap for reconstruction of the chest wall after soft tissue necrosis following epirubicin extravasation.

Expression of DMP-1 in the human pulp tissue using low level laser therapy

NASA Astrophysics Data System (ADS)

Lourenço Neto, Natalino; Teixeira Marques, Nádia Carolina; Fernandes, Ana Paula; Oliveira Rodini, Camila; Cruvinel Silva, Thiago; Moreira Machado, Maria Aparecida Andrade; Marchini Oliveira, Thais

2015-09-01

This study aimed to evaluate the effects of low-level laser therapy (LLLT) on DMP-1 expression in pulp tissue repair of human primary teeth. Twenty mandibular primary molars were randomly assigned into the following groups: Group I—Buckley’s Formocresol (FC); Group II—Calcium Hydroxide (CH); Group III—LLLT + CH and Group IV—LLLT + Zinc oxide/Eugenol. The teeth at the regular exfoliation period were extracted for histological analysis and immunolocalization of DMP-1. Descriptive analysis was performed on the dentin pulp complex. Histopathological assessment showed internal resorption in group FC. Groups CH and LLLT + CH provided better pulpal repair due to the absence of inflammation and the formation of hard tissue barrier. These two groups presented odontoblastic layer expressing DMP-1. According to this study, low level laser therapy preceding the use of calcium hydroxide exhibited satisfactory bio-inductive activity on pulp tissue repair of human primary teeth. However, other histological and cellular studies are needed to confirm the laser tissue action and efficacy.

Oncologic photodynamic diagnosis and therapy: confocal Raman/fluorescence imaging of metal phthalocyanines in human breast cancer tissue in vitro.

PubMed

Abramczyk, Halina; Brozek-Pluska, Beata; Surmacki, Jakub; Musial, Jacek; Kordek, Radzislaw

2014-11-07

Raman microspectroscopy and confocal Raman imaging combined with confocal fluorescence were used to study the distribution and aggregation of aluminum tetrasulfonated phthalocyanine (AlPcS4) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and aggregation of aluminum phthalocyanine, which is a potential photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. We have observed that the distribution of aluminum tetrasulfonated phthalocyanine confined in cancerous tissue is markedly different from that in noncancerous tissue. We have concluded that Raman imaging can be treated as a new and powerful technique useful in cancer photodynamic therapy, increasing our understanding of the mechanisms and efficiency of photosensitizers by better monitoring localization in cancer cells as well as the clinical assessment of the therapeutic effects of PDT and PIT.

Acoustic pressure wound therapy to facilitate granulation tissue in sacral pressure ulcers in patients with compromised mobility: a case series.

PubMed

Schmuckler, Jo

2008-08-01

Electrical stimulation and other modalities are recommended for treatment of pressure ulcers in spinal cord injury patients but their use may be limited by clinical contraindications such as necrosis and infection. Acoustic pressure wound therapy can be used to address infection and has no known contraindications related to wound status. A retrospective nonconsecutive study was conducted involving five inpatients with sacral pressure ulcers and compromised mobility (spinal cord injury, ventilator/mobility dependency, or persistent vegetative state) treated with acoustic pressure wound therapy three times per week, 4 to 6 minutes per session, for 5 weeks to 5.5 months. Acoustic pressure wound therapy was administered until necrotic tissue was removed, granulation was complete, drainage resolved to moderate levels, and wound size was compatible with indications for high-voltage electrical stimulation. Within 1 to 4 weeks of starting acoustic pressure wound therapy, four out of five wounds with substantial yellow slough or eschar demonstrated 100% granulation tissue and wound area and volume decreased 71% to 97% and 75% to 99%, respectively. Subsequent treatments included electrical stimulation alone (three patients) or in conjunction with negative pressure wound therapy (one patient), and silver foam (one patient). Acoustic pressure wound therapy was found to be an effective option in preparing wounds for subsequent therapy.

Periodontal tissue regeneration by combined implantation of adipose tissue-derived stem cells and platelet-rich plasma in a canine model.

PubMed

Tobita, Morikuni; Uysal, Cagri A; Guo, Xin; Hyakusoku, Hiko; Mizuno, Hiroshi

2013-12-01

One goal of periodontal therapy is to regenerate periodontal tissues. Stem cells, growth factors and scaffolds and biomaterials are vital for the restoration of the architecture and function of complex tissues. Adipose tissue-derived stem cells (ASCs) are an ideal population of stem cells for practical regenerative medicine. In addition, platelet-rich plasma (PRP) can be useful for its ability to stimulate tissue regeneration. PRP contains various growth factors and may be useful as a cell carrier in stem cell therapies. The purpose of this study was to determine whether a mixture of ASCs and PRP promoted periodontal tissue regeneration in a canine model. Autologous ASCs and PRP were implanted into areas with periodontal tissue defects. Periodontal tissue defects that received PRP alone or non-implantation were also examined. Histologic, immunohistologic and x-ray studies were performed 1 or 2 months after implantation. The amount of newly formed bone and the scale of newly formed cementum in the region of the periodontal tissue defect were analyzed on tissue sections. The areas of newly formed bone and cementum were greater 2 months after implantation of ASCs and PRP than at 1 month after implantation, and the radiopacity in the region of the periodontal tissue defect increased markedly by 2 months after implantation. The ASCs and PRP group exhibited periodontal tissue with the correct architecture, including alveolar bone, cementum-like structures and periodontal ligament-like structures, by 2 months after implantation. These findings suggest that a combination of autologous ASCs and PRP promotes periodontal tissue regeneration that develops the appropriate architecture for this complex tissue. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The role of nanotechnology in induced pluripotent and embryonic stem cells research.

PubMed

Chen, Lukui; Qiu, Rong; Li, Lushen

2014-12-01

This paper reviews the recent studies on development of nanotechnology in the field of induced pluripotent and embryonic stem cells. Stem cell therapy is a promising therapy that can improve the quality of life for patients with refractory diseases. However, this option is limited by the scarcity of tissues, ethical problem, and tumorigenicity. Nanotechnology is another promising therapy that can be used to mimic the extracellular matrix, label the implanted cells, and also can be applied in the tissue engineering. In this review, we briefly introduce implementation of nanotechnology in induced pluripotent and embryonic stem cells research. Finally, the potential application of nanotechnology in tissue engineering and regenerative medicine is also discussed.

Potential for Stem Cell-Based Periodontal Therapy

PubMed Central

Bassir, Seyed Hossein; Wisitrasameewong, Wichaya; Raanan, Justin; Ghaffarigarakani, Sasan; Chung, Jamie; Freire, Marcelo; Andrada, Luciano C.; Intini, Giuseppe

2015-01-01

Periodontal diseases are highly prevalent and are linked to several systemic diseases. The goal of periodontal treatment is to halt the progression of the disease and regenerate the damaged tissue. However, achieving complete and functional periodontal regeneration is challenging because the periodontium is a complex apparatus composed of different tissues, including bone, cementum, and periodontal ligament. Stem cell-based regenerative therapy may represent an effective therapeutic tool for periodontal regeneration due to their plasticity and ability to differentiate into different cell lineages. This review presents and critically analyzes the available information on stem cell-based therapy for the regeneration of periodontal tissues and suggests new avenues for the development of more effective therapeutic protocols. PMID:26058394

[CHANGES IN THE ORGANS AND TISSUES OF THE ORAL CAVITY WITH DIGESTIVE SYSTEM DISEASES].

PubMed

Trukhan, D I; Goloshubina, V V; Trukhan, L Yu

2015-01-01

A substantial part of the pathology of organs and tissues of the oral cavity make common manifestations or systemic diseases. Accordingly, the dosage systemic therapy of these diseases can affect the condition of the eye. Changes in organs and tissues of the oral cavity and the appropriate advice a dentist can help the gastroenterologist in the diagnosis and adequate treatment of the patient. The article discusses possible changes in the organs and tissues of the oral cavity in diseases of the digestive system, as well as changes occurring under the influence of drug therapy of these diseases.

Tissue engineering therapy for cardiovascular disease.

PubMed

Nugent, Helen M; Edelman, Elazer R

2003-05-30

The present treatments for the loss or failure of cardiovascular function include organ transplantation, surgical reconstruction, mechanical or synthetic devices, or the administration of metabolic products. Although routinely used, these treatments are not without constraints and complications. The emerging and interdisciplinary field of tissue engineering has evolved to provide solutions to tissue creation and repair. Tissue engineering applies the principles of engineering, material science, and biology toward the development of biological substitutes that restore, maintain, or improve tissue function. Progress has been made in engineering the various components of the cardiovascular system, including blood vessels, heart valves, and cardiac muscle. Many pivotal studies have been performed in recent years that may support the move toward the widespread application of tissue-engineered therapy for cardiovascular diseases. The studies discussed include endothelial cell seeding of vascular grafts, tissue-engineered vascular conduits, generation of heart valve leaflets, cardiomyoplasty, genetic manipulation, and in vitro conditions for optimizing tissue-engineered cardiovascular constructs.

Photothermal lesions in soft tissue induced by optical fiber microheaters.

PubMed

Pimentel-Domínguez, Reinher; Moreno-Álvarez, Paola; Hautefeuille, Mathieu; Chavarría, Anahí; Hernández-Cordero, Juan

2016-04-01

Photothermal therapy has shown to be a promising technique for local treatment of tumors. However, the main challenge for this technique is the availability of localized heat sources to minimize thermal damage in the surrounding healthy tissue. In this work, we demonstrate the use of optical fiber microheaters for inducing thermal lesions in soft tissue. The proposed devices incorporate carbon nanotubes or gold nanolayers on the tips of optical fibers for enhanced photothermal effects and heating of ex vivo biological tissues. We report preliminary results of small size photothermal lesions induced on mice liver tissues. The morphology of the resulting lesions shows that optical fiber microheaters may render useful for delivering highly localized heat for photothermal therapy.

RADIATION THERAPY COMMUNICATION-REIRRADIATION OF A NASAL TUMOR IN A BRACHYCEPHALIC DOG USING INTENSITY MODULATED RADIATION THERAPY.

PubMed

Rancilio, Nicholas J; Custead, Michelle R; Poulson, Jean M

2016-09-01

A 5-year-old spayed female Shih Tzu was referred for evaluation of a nasal transitional carcinoma. A total lifetime dose of 117 Gy was delivered to the intranasal mass in three courses over nearly 2 years using fractionated intensity modulated radiation therapy (IMRT) to spare normal tissues. Clinically significant late normal tissue side effects were limited to bilaterally diminished tear production. The patient died of metastatic disease progression 694 days after completion of radiation therapy course 1. This case demonstrates that retreatment with radiation therapy to high lifetime doses for recurrent local disease may be well tolerated with IMRT. © 2016 American College of Veterinary Radiology.

Optoacoustic detection of thermal lesions

NASA Astrophysics Data System (ADS)

Arsenault, Michel G.; Kolios, Michael C.; Whelan, William M.

2009-02-01

Minimally invasive thermal therapy is being investigated as an alternative cancer treatment. It involves heating tissues to greater than 55°C over a period of a few minutes, which results in tissue coagulation. Optoacoustic (OA) imaging is a new imaging technique that involves exposing tissues to pulsed light and detecting the acoustic waves that are generated. In this study, adult bovine liver tissue samples were heated using continuous wave laser energy for various times, then scanned using an optoacoustic imaging system. Large optoacoustic signal variability was observed in the native tissue prior to heating. OA signal amplitude increased with maximum tissue temperature achieved, characterized by a correlation coefficient of 0.63. In this study we show that there are detectable changes in optoacoustic signal strength that arise from tissue coagulation, which demonstrates the potential of optoacoustic technology for the monitoring of thermal therapy delivery.

Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer

DTIC Science & Technology

2013-09-01

has been identified in various human tumor tissues, including cancers of the breast, ovary, oropharynx, and esophagus , and has predicted poor patient...been identified in various human tumor tissues, including cancers of the breast, ovary, oropharynx, and esophagus , and has predicted...Improving Cetuximab Therapy in Lung Cancer PRINCIPAL INVESTIGATOR: Deric L Wheeler

AAV vector encoding human VEGF165-transduced pectineus muscular flaps increase the formation of new tissue through induction of angiogenesis in an in vivo chamber for tissue engineering: A technique to enhance tissue and vessels in microsurgically engineered tissue.

PubMed

Moimas, Silvia; Manasseri, Benedetto; Cuccia, Giuseppe; Stagno d'Alcontres, Francesco; Geuna, Stefano; Pattarini, Lucia; Zentilin, Lorena; Giacca, Mauro; Colonna, Michele R

2015-01-01

In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen-glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene β-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine.

Protective effect of gel form of gastric gavage applicated aloe vera on ischemia reperfusion injury in renal and lung tissue.

PubMed

Sahin, Hasan; Yener, Ali Umit; Karaboga, Ihsan; Sehitoglu, Muserref Hilal; Dogu, Tugba; Altinisik, Hatice Betul; Altinisik, Ugur; Simsek, Tuncer

2017-12-30

The aloe vera plant has become increasingly popular in recent years. This study aimed to research the effect of aloe vera to prevent renal and lung tissue damage in an experimental ischemia-reperfusion (I/R) injury model. The study included 21 male Wistar Albino rats, which were categorized into control group, n = 7 (no procedures), Sham group n = 7 (I/R); and aloe vera therapy group, n = 7 (aloe vera and I/R). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were evaluated from lung and kidney tissues for biochemical investigations. As histopathological, hematoxylin and eosin and anti-iNOS were also examined. In biochemical investigations, SOD, CAT, and GPx levels of the Sham group were found to be lower compared with the other groups (P < 0.05). The aloe vera therapy group was not statistically different from control groups but significantly different compared with the Sham group. In the same way, the MDA levels of kidney and lung tissues were statistically significant in the aloe vera therapy group, compared to the Sham group. In the Sham group, the peribronchial and perialveolar edema were observed in lung parenchyma. Also, excess interstitial hemorrhage, leukocyte infiltration, and alveolar wall thickening were identified in ischemic groups. The histopathological changes were much lighter than in the aloe vera therapy group. In renal tissues, excess epithelial cell deterioration, tubular desqumination, and glomerular atrophy were observed in the Sham group. The histopathological changes were markedly reduced in the aloe vera therapy  group. In the kidney and lung tissue, the level of iNOS activity in the Sham group was significantly higher than in the control and aloe vera therapy group. This study indicated that aloe vera is protective against oxidative damage formed by I/R in distant organs like the lungs and kidneys.

Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

PubMed

Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

2015-01-01

Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

LATIS3D: The Goal Standard for Laser-Tissue-Interaction Modeling

NASA Astrophysics Data System (ADS)

London, R. A.; Makarewicz, A. M.; Kim, B. M.; Gentile, N. A.; Yang, T. Y. B.

2000-03-01

The goal of this LDRD project has been to create LATIS3D-the world's premier computer program for laser-tissue interaction modeling. The development was based on recent experience with the 2D LATIS code and the ASCI code, KULL. With LATIS3D, important applications in laser medical therapy were researched including dynamical calculations of tissue emulsification and ablation, photothermal therapy, and photon transport for photodynamic therapy. This project also enhanced LLNL's core competency in laser-matter interactions and high-energy-density physics by pushing simulation codes into new parameter regimes and by attracting external expertise. This will benefit both existing LLNL programs such as ICF and SBSS and emerging programs in medical technology and other laser applications. The purpose of this project was to develop and apply a computer program for laser-tissue interaction modeling to aid in the development of new instruments and procedures in laser medicine.

Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

PubMed Central

Yoshida, Toshiyuki; Washio, Kaoru; Iwata, Takanori; Okano, Teruo; Ishikawa, Isao

2012-01-01

It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy. PMID:22315604

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

NASA Astrophysics Data System (ADS)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

Image-guided therapies for myocardial repair: concepts and practical implementation

PubMed Central

Bengel, Frank M.; George, Richard T.; Schuleri, Karl H.; Lardo, Albert C.; Wollert, Kai C.

2013-01-01

Cell- and molecule-based therapeutic strategies to support wound healing and regeneration after myocardial infarction (MI) are under development. These emerging therapies aim at sustained preservation of ventricular function by enhancing tissue repair after myocardial ischaemia and reperfusion. Such therapies will benefit from guidance with regard to timing, regional targeting, suitable candidate selection, and effectiveness monitoring. Such guidance is effectively obtained by non-invasive tomographic imaging. Infarct size, tissue characteristics, muscle mass, and chamber geometry can be determined by magnetic resonance imaging and computed tomography. Radionuclide imaging can be used for the tracking of therapeutic agents and for the interrogation of molecular mechanisms such as inflammation, angiogenesis, and extracellular matrix activation. This review article portrays the hypothesis that an integrated approach with an early implementation of structural and molecular tomographic imaging in the development of novel therapies will provide a framework for achieving the goal of improved tissue repair after MI. PMID:23720377

Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

PubMed Central

Kim, Yi Rang; Kim, Seonghoon; Choi, Jin Woo; Choi, Sung Yong; Lee, Sang-Hee; Kim, Homin; Hahn, Sei Kwang; Koh, Gou Young; Yun, Seok Hyun

2015-01-01

Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm2 for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT. PMID:26000054

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myoribers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Telmisartan Therapy Does Not Improve Lymph Node or Adipose Tissue Fibrosis More Than Continued Antiretroviral Therapy Alone.

PubMed

Utay, Netanya S; Kitch, Douglas W; Yeh, Eunice; Fichtenbaum, Carl J; Lederman, Michael M; Estes, Jacob D; Deleage, Claire; Magyar, Clara; Nelson, Scott D; Klingman, Karen L; Bastow, Barbara; Luque, Amneris E; McComsey, Grace A; Douek, Daniel C; Currier, Judith S; Lake, Jordan E

2018-05-05

Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. In this 48-week, randomized, controlled trial, adults continued HIV-suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was -2.6 percentage points (P = 0.08) in lymph node specimens and -1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by -0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (-1.0 percentage point; P = .001) and fibronectin deposition (-2.4 percentage points; P < .001) were observed, with no between-arm differences. In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.

Comparative dosimetry of volumetric modulated arc therapy and limited-angle static intensity-modulated radiation therapy for early-stage larynx cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riegel, Adam C.; Antone, Jeffrey; Schwartz, David L., E-mail: dschwartz3@nshs.edu

2013-04-01

To compare relative carotid and normal tissue sparing using volumetric-modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) for early-stage larynx cancer. Seven treatment plans were retrospectively created on 2 commercial treatment planning systems for 11 consecutive patients with T1-2N0 larynx cancer. Conventional plans consisted of opposed-wedged fields. IMRT planning used an anterior 3-field beam arrangement. Two VMAT plans were created, a full 360° arc and an anterior 180° arc. Given planning target volume (PTV) coverage of 95% total volume at 95% of 6300 cGy and maximum spinal cord dose below 2500 cGy, mean carotid artery dose was pushed asmore » low as possible for each plan. Deliverability was assessed by comparing measured and planned planar dose with the gamma (γ) index. Full-arc planning provided the most effective carotid sparing but yielded the highest mean normal tissue dose (where normal tissue was defined as all soft tissue minus PTV). Static IMRT produced next-best carotid sparing with lower normal tissue dose. The anterior half-arc produced the highest carotid artery dose, in some cases comparable with conventional opposed fields. On the whole, carotid sparing was inversely related to normal tissue dose sparing. Mean γ indexes were much less than 1, consistent with accurate delivery of planned treatment. Full-arc VMAT yields greater carotid sparing than half-arc VMAT. Limited-angle IMRT remains a reasonable alternative to full-arc VMAT, given its ability to mediate the competing demands of carotid and normal tissue dose constraints. The respective clinical significance of carotid and normal tissue sparing will require prospective evaluation.« less

Optimizing Results of Postmastectomy Radiation Therapy Utilizing the Latissimus Dorsi Flap and Tissue Expander Technique: A Single-Center Experience

PubMed Central

Chevrollier, Guillaume S.; Greaney, Patrick J.; Jenkins, Matthew P.; Copit, Steven E.

2017-01-01

Objective: Postmastectomy radiation therapy is a well-established risk factor for complications after breast reconstruction. Even if the surgeon has a suspicion that radiation therapy may be needed, it may be beneficial to place tissue expanders during the mastectomy procedure as a temporizing measure, complete radiation therapy, and then reconstruct the breast with a latissimus flap. The purpose of this study was to examine the complication rates of the latissimus dorsi flap as compared with the complication rates of implant-based reconstruction in the setting of radiation therapy. Methods: A 16-year retrospective chart review from 2000 to 2016 was conducted. All patients who underwent temporizing tissue expander placement for radiotherapy with subsequent latissimus flap reconstruction were included in the study. Patients who did not follow up for implant exchange were excluded from the study. Results: Fifty-five patients were identified with an average age of 46.0 years (range, 27-67 years) and an average body mass index of 24.2 (range, 18.9-31.9). Five patients (9.1%) developed capsular contractures amenable to surgical intervention. One patient (1.8%) developed infection of the tissue expander, requiring removal. There were no incidences of flap failure or wound dehiscence. The average follow-up after latissimus flap reconstruction was 25.3 months (range, 3.7-121.6 months). Conclusions: We feel that the latissimus dorsi flap after postmastectomy radiation therapy represents the preferred implant-based reconstruction option to consider when the need for postmastectomy radiation therapy is anticipated. The latissimus dorsi flap remains a safe, effective solution to postmastectomy radiation therapy that every plastic surgeon should offer. PMID:29308108

Optimizing Results of Postmastectomy Radiation Therapy Utilizing the Latissimus Dorsi Flap and Tissue Expander Technique: A Single-Center Experience.

PubMed

Mohiuddin, Waseem; Chevrollier, Guillaume S; Greaney, Patrick J; Jenkins, Matthew P; Copit, Steven E

2017-01-01

Objective: Postmastectomy radiation therapy is a well-established risk factor for complications after breast reconstruction. Even if the surgeon has a suspicion that radiation therapy may be needed, it may be beneficial to place tissue expanders during the mastectomy procedure as a temporizing measure, complete radiation therapy, and then reconstruct the breast with a latissimus flap. The purpose of this study was to examine the complication rates of the latissimus dorsi flap as compared with the complication rates of implant-based reconstruction in the setting of radiation therapy. Methods: A 16-year retrospective chart review from 2000 to 2016 was conducted. All patients who underwent temporizing tissue expander placement for radiotherapy with subsequent latissimus flap reconstruction were included in the study. Patients who did not follow up for implant exchange were excluded from the study. Results: Fifty-five patients were identified with an average age of 46.0 years (range, 27-67 years) and an average body mass index of 24.2 (range, 18.9-31.9). Five patients (9.1%) developed capsular contractures amenable to surgical intervention. One patient (1.8%) developed infection of the tissue expander, requiring removal. There were no incidences of flap failure or wound dehiscence. The average follow-up after latissimus flap reconstruction was 25.3 months (range, 3.7-121.6 months). Conclusions: We feel that the latissimus dorsi flap after postmastectomy radiation therapy represents the preferred implant-based reconstruction option to consider when the need for postmastectomy radiation therapy is anticipated. The latissimus dorsi flap remains a safe, effective solution to postmastectomy radiation therapy that every plastic surgeon should offer.

Determining the appropriate number and duration of leech therapy in congested tissues using tissue spectrophotometry and laser Doppler flowmetry.

PubMed

Rothenberger, Jens; Petersen, Wiebke; Schaller, Hans-Eberhard; Held, Manuel

2016-11-01

A universal protocol determining the number of leeches and their application time does not exist. The aim of this study, therefore, is to quantify perfusion dynamics in venous congested tissues after leech application to get more detailed information about changes due to leech-induced skin microcirculation and to evaluate the usability of the Oxygen to See (O2C) device in terms of determining the appropriate number of leeches and the duration of therapy. Twelve patients with the need for leech therapy participated in the study. Perfusion dynamics of the congested tissue was assessed using the O2C device, which determines blood flow (BF), the relative amount of hemoglobin (rHB), and the oxygen saturation (SO2). Measurements were carried out before leech application and on various intervals like 10 minutes, one hour, and three hours after leech application. The leech application effectuated after 10 minutes a nonsignificant perfusion improvement, which further increased after one hour with a significant reduction of the relative amount of hemoglobin and a significant increase of blood flow and oxygen saturation (BF= +56.7%; rHB= -25.5%; SO2= +53.7%). After three hours, the values returned to the levels before leech administration. In two cases, in which further administration of leeches within the measurement period was necessary, no substantial perfusion changes were obtained. The results of this study forms a more precise pattern of microcirculatory changes of leech therapy in congested tissues. According to our measurements a venous drainage improvement can be expected in congested tissue one hour after leech administration. The O2C seems to be a useful method to determine the appropriate number and duration of leech therapy. © 2016 by the Wound Healing Society.

Joint and Soft Tissue Injections

MedlinePlus

... TestingRead Article >>Plasma Viral Load TestingInsulin TherapyRead Article >>Insulin Therapy Visit our interactive symptom checker Visit our interactive symptom checker Get Started Related ArticlesPlasma Viral Load TestingRead ... TherapyRead Article >>Drugs, Procedures & DevicesInsulin TherapyThe goal of ...

Solid tumors.

PubMed

Richardson, R C

1985-05-01

Soft-tissue tumors are similar in their behavior. Benign tumors can be easily resected in most cases, whereas malignant tumors are relentless in their locally invasive characteristics. A clear understanding of the constraints of the pathologist in reaching a confirmed diagnosis and a logical plan utilizing surgery as the major modality of therapy are necessary for successful management of these tumors. It appears that radiation combined with hyperthermia is beginning to play a significant role in the local control of soft-tissue sarcomas and that single or multi-agent chemotherapy may be of benefit in treatment of nonresectable or metastatic soft-tissue sarcomas. For the immediate future, surgery remains the only nonexperimental modality of therapy, but the rapid advances in the other therapy methods are encouraging.

Long-Term Results Comparing Xenogeneic Collagen Matrix and Autogenous Connective Tissue Grafts With Coronally Advanced Flaps for Treatment of Dehiscence-Type Recession Defects.

PubMed

McGuire, Michael K; Scheyer, E Todd

2016-03-01

Although connective tissue grafts with coronally advanced flaps (CTG + CAF) have been deemed the gold standard for recession defect treatment, to provide adequate recession coverage, the periodontal profession continues to pursue lower-morbidity, patient-preferred substitutes that are more convenient and of unlimited supply. Using a randomized, controlled, and masked contralateral comparison of matched-pair, within-patient recession defects, collagen matrix (CMX) + CAF therapy was compared with CTG + CAF at 6 months and 5 years. The primary efficacy endpoint was percentage of root coverage (RC). Secondary efficacy parameters included width of keratinized tissue (KTw), probing depth (PD), clinical attachment level (CAL), clinician rating of color and texture compared with surrounding tissues, and patient esthetic satisfaction. Seventeen patients were available for the 5-year recall. Mean RC between 6 months and 5 years changed from 89.5% to 77.6% for CMX + CAF test sites and 97.5% to 95.5% for CTG + CAF control sites. KTw averaged >3 mm for both test and control sites at 5 years. PD was equivalent at all time points. The 6-month to 5-year changes for RC, KTw, and PD were not significantly different between therapies. CAL change from 6 months to 5 years was greater for CTG + CAF (0.26 mm) than CMX + CAF (-0.21 mm). Tissue color match to surrounding tissues remained similar for both therapies throughout the study. There was a difference in tissue texture at both 6 months and 5 years, with CMX + CAF sites tending to be "equally firm" and CTG + CAF sites "more firm." Patient satisfaction was high, with no statistical difference in satisfaction between therapies at any time point. When balanced with patient-reported satisfaction, clinical rankings of esthetics, and control and historical RC results reported by other investigators, CMX + CAF appears to present a viable and long-term alternative to traditional CTG + CAF therapy.

Value of MR contrast media in image-guided body interventions.

PubMed

Saeed, Maythem; Wilson, Mark

2012-01-28

In the past few years, there have been multiple advances in magnetic resonance (MR) instrumentation, in vivo devices, real-time imaging sequences and interventional procedures with new therapies. More recently, interventionists have started to use minimally invasive image-guided procedures and local therapies, which reduce the pain from conventional surgery and increase drug effectiveness, respectively. Local therapy also reduces the systemic dose and eliminates the toxic side effects of some drugs to other organs. The success of MR-guided procedures depends on visualization of the targets in 3D and precise deployment of ablation catheters, local therapies and devices. MR contrast media provide a wealth of tissue contrast and allows 3D and 4D image acquisitions. After the development of fast imaging sequences, the clinical applications of MR contrast media have been substantially expanded to include pre- during- and post-interventions. Prior to intervention, MR contrast media have the potential to localize and delineate pathologic tissues of vital organs, such as the brain, heart, breast, kidney, prostate, liver and uterus. They also offer other options such as labeling therapeutic agents or cells. During intervention, these agents have the capability to map blood vessels and enhance the contrast between the endovascular guidewire/catheters/devices, blood and tissues as well as direct therapies to the target. Furthermore, labeling therapeutic agents or cells aids in visualizing their delivery sites and tracking their tissue distribution. After intervention, MR contrast media have been used for assessing the efficacy of ablation and therapies. It should be noted that most image-guided procedures are under preclinical research and development. It can be concluded that MR contrast media have great value in preclinical and some clinical interventional procedures. Future applications of MR contrast media in image-guided procedures depend on their safety, tolerability, tissue specificity and effectiveness in demonstrating success of the interventions and therapies.

Non-invasive assessment of negative pressure wound therapy using high frequency diagnostic ultrasound: oedema reduction and new tissue accumulation.

PubMed

Young, Stephen R; Hampton, Sylvie; Martin, Robin

2013-08-01

Tissue oedema plays an important role in the pathology of chronic and traumatic wounds. Negative pressure wound therapy (NPWT) is thought to contribute to active oedema reduction, yet few studies have showed this effect. In this study, high frequency diagnostic ultrasound at 20 MHz with an axial resolution of 60 µm was used to assess the effect of NPWT at - 80 mmHg on pressure ulcers and the surrounding tissue. Wounds were monitored in four patients over a 3-month period during which changes in oedema and wound bed thickness (granulation tissue) were measured non-invasively. The results showed a rapid reduction of periwound tissue oedema in all patients with levels falling by a mean of 43% after 4 days of therapy. A 20% increase in the thickness of the wound bed was observed after 7 days due to new granulation tissue formation. Ultrasound scans through the in situ gauze NPWT filler also revealed the existence of macrodeformation in the tissue produced by the negative pressure. These preliminary studies suggest that non-invasive assessment using high frequency diagnostic ultrasound could be a valuable tool in clinical studies of NPWT. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Method for microbeam radiation therapy

DOEpatents

Slatkin, Daniel N.; Dilmanian, F. Avraham; Spanne, Per O.

1994-01-01

A method of performing radiation therapy on a patient, involving exposing a target, usually a tumor, to a therapeutic dose of high energy electromagnetic radiation, preferably X-ray radiation, in the form of at least two non-overlapping microbeams of radiation, each microbeam having a width of less than about 1 millimeter. Target tissue exposed to the microbeams receives a radiation dose during the exposure that exceeds the maximum dose that such tissue can survive. Non-target tissue between the microbeams receives a dose of radiation below the threshold amount of radiation that can be survived by the tissue, and thereby permits the non-target tissue to regenerate. The microbeams may be directed at the target from one direction, or from more than one direction in which case the microbeams overlap within the target tissue enhancing the lethal effect of the irradiation while sparing the surrounding healthy tissue.

Method for microbeam radiation therapy

DOEpatents

Slatkin, D.N.; Dilmanian, F.A.; Spanne, P.O.

1994-08-16

A method is disclosed of performing radiation therapy on a patient, involving exposing a target, usually a tumor, to a therapeutic dose of high energy electromagnetic radiation, preferably X-ray radiation. The dose is in the form of at least two non-overlapping microbeams of radiation, each microbeam having a width of less than about 1 millimeter. Target tissue exposed to the microbeams receives a radiation dose during the exposure that exceeds the maximum dose that such tissue can survive. Non-target tissue between the microbeams receives a dose of radiation below the threshold amount of radiation that can be survived by the tissue, and thereby permits the non-target tissue to regenerate. The microbeams may be directed at the target from one direction, or from more than one direction in which case the microbeams overlap within the target tissue enhancing the lethal effect of the irradiation while sparing the surrounding healthy tissue. No Drawings

Tissue engineering in urothelium regeneration.

PubMed

Vaegler, Martin; Maurer, Sabine; Toomey, Patricia; Amend, Bastian; Sievert, Karl-Dietrich

2015-03-01

The development of therapeutic treatments to regenerate urothelium, manufacture tissue equivalents or neourethras for in-vivo application is a significant challenge in the field of tissue engineering. Many studies have focused on urethral defects that, in most cases, inadequately address current therapies. This article reviews the primary tissue engineering strategies aimed at the clinical requirements for urothelium regeneration while concentrating on promising investigations in the use of grafts, cellular preparations, as well as seeded or unseeded natural and synthetic materials. Despite significant progress being made in the development of scaffolds and matrices, buccal mucosa transplants have not been replaced. Recently, graft tissues appear to have an advantage over the use of matrices. These therapies depend on cell isolation and propagation in vitro that require, not only substantial laboratory resources, but also subsequent surgical implant procedures. The choice of the correct cell source is crucial when determining an in-vivo application because of the risks of tissue changes and abnormalities that may result in donor site morbidity. Addressing an appropriately-designed animal model and relevant regulatory issues is of fundamental importance for the principal investigators when a therapy using cellular components has been developed for clinical use. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical application of cell, gene and tissue therapies in Spain.

PubMed

Gálvez-Martín, P; Ruiz, A; Clares, B

2018-05-01

Scientific and technical advances in the areas of biomedicine and regenerative medicine have enabled the development of new treatments known as "advanced therapies", which encompass cell therapy, genetics and tissue engineering. The biologic products that can be manufactured from these elements are classified from the standpoint of the Spanish Agency of Medication and Health Products in advanced drug therapies, blood products and transplants. This review seeks to provide scientific and administrative information for clinicians on the use of these biologic resources. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Manual therapy for plantar heel pain.

PubMed

Pollack, Yosefa; Shashua, Anat; Kalichman, Leonid

2018-03-01

Manual therapy employed in the treatment of plantar heel pain includes joint or soft tissue mobilizations. Efficacy of these methods is still under debate. To determine whether manual therapy, consisting of deep massage, myofascial release or joint mobilization is effective in treating plantar heel pain. A critical review of all available studies with an emphasis on randomized controlled trials (RCTs) was performed. PubMed, PEDro, and Google Scholar databases were searched for keywords relating to plantar heel pain, joint, and soft tissue mobilizations. There were no search limitations or language restrictions. The reference lists of all retrieved articles were searched. The PEDro score was used to assess the quality of the reviewed papers. A total of six relevant RCTs were found: two examined the effectiveness of joint mobilization on plantar heel pain and four the effectiveness of soft tissue techniques. Five studies showed a positive short-term effect after manual therapy treatment, mostly soft tissue mobilizations, with or without stretching exercises for patients with plantar heel pain, compared to other treatments. One study observed that adding joint mobilization to the treatment of plantar heel pain was not effective. The quality of all studies was moderate to high. According to reviewed moderate and high-quality RCTs, soft tissue mobilization is an effective modality for treating plantar heel pain. Outcomes of joint mobilizations are controversial. Further studies are needed to evaluate the short and long-term effect of different soft tissue mobilization techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Emerging Roles for Extracellular Vesicles in Tissue Engineering and Regenerative Medicine

PubMed Central

Lamichhane, Tek N.; Sokic, Sonja; Schardt, John S.; Raiker, Rahul S.; Lin, Jennifer W.

2015-01-01

Extracellular vesicles (EVs)—comprising a heterogeneous population of cell-derived lipid vesicles including exosomes, microvesicles, and others—have recently emerged as both mediators of intercellular information transfer in numerous biological systems and vehicles for drug delivery. In both roles, EVs have immense potential to impact tissue engineering and regenerative medicine applications. For example, the therapeutic effects of several progenitor and stem cell-based therapies have been attributed primarily to EVs secreted by these cells, and EVs have been recently reported to play direct roles in injury-induced tissue regeneration processes in multiple physiological systems. In addition, EVs have been utilized for targeted drug delivery in regenerative applications and possess unique potential to be harnessed as patient-derived drug delivery vehicles for personalized medicine. This review discusses EVs in the context of tissue repair and regeneration, including their utilization as drug carriers and their crucial role in cell-based therapies. Furthermore, the article highlights the growing need for bioengineers to understand, consider, and ultimately design and specifically control the activity of EVs to maximize the efficacy of tissue engineering and regenerative therapies. PMID:24957510

Deep tissue massage: What are we talking about?

PubMed

Koren, Yogev; Kalichman, Leonid

2018-04-01

Massage is a common treatment in complementary and integrative medicine. Deep tissue massage, a form of therapeutic massage, has become more and more popular in recent years. Hence, the use of massage generally and deep tissue massage specifically, should be evaluated as any other modality of therapy to establish its efficacy and safety. To determine the definitions used for deep tissue massage in the scientific literature and to review the current scientific evidence for its efficacy and safety. Narrative review. There is no commonly accepted definition of deep tissue massage in the literature. The definition most frequently used is the intention of the therapist. We suggest separating the definitions of deep massage and deep tissue massage as follows: deep massage should be used to describe the intention of the therapist to treat deep tissue by using any form of massage and deep tissue massage should be used to describe a specific and independent method of massage therapy, utilizing the specific set of principles and techniques as defined by Riggs: "The understanding of the layers of the body, and the ability to work with tissue in these layers to relax, lengthen, and release holding patterns in the most effective and energy efficient way possible within the client's parameters of comfort". Heterogeneity of techniques and protocols used in published studies have made it difficult to draw any clear conclusions. Favorable outcomes may result from deep tissue massage in pain populations and patients with decreased range of motion. In addition, several rare serious adverse events were found related to deep tissue massage, probably as a result of the forceful application of massage therapy. Future research of deep tissue massage should be based on a common definition, classification system and the use of common comparators as controls. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypoxia as a target for tissue specific gene therapy.

PubMed

Rhim, Taiyoun; Lee, Dong Yun; Lee, Minhyung

2013-12-10

Hypoxia is a hallmark of various ischemic diseases such as ischemic heart disease, ischemic limb, ischemic stroke, and solid tumors. Gene therapies for these diseases have been developed with various therapeutic genes including growth factors, anti-apoptotic genes, and toxins. However, non-specific expression of these therapeutic genes may induce dangerous side effects in the normal tissues. To avoid the side effects, gene expression should be tightly regulated in an oxygen concentration dependent manner. The hypoxia inducible promoters and enhancers have been evaluated as a transcriptional regulation tool for hypoxia inducible gene therapy. The hypoxia inducible UTRs were also used in gene therapy for spinal cord injury as a translational regulation strategy. In addition to transcriptional and translational regulations, post-translational regulation strategies have been developed using the HIF-1α ODD domain. Hypoxia inducible transcriptional, translational, and post-translational regulations are useful for tissue specific gene therapy of ischemic diseases. In this review, hypoxia inducible gene expression systems are discussed and their applications are introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy

PubMed Central

Peterson, Christopher W.; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Holmes, Michael C.; Estes, Jacob D.

2018-01-01

Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents. PMID:29672640

Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis

PubMed Central

Darlington, Peter J; Boivin, Marie-Noëlle; Bar-Or, Amit

2011-01-01

Phase I clinical trials exploring the use of autologous mesenchymal stem cell (MSC) therapy for the treatment of multiple sclerosis (MS) have begun in a number of centers across the world. MS is a complex and chronic immune-mediated and neurodegenerative disease influenced by genetic susceptibility and environmental risk factors. The ideal treatment for MS would involve both attenuation of detrimental inflammatory responses, and induction of a degree of tissue protection/regeneration within the CNS. Preclinical studies have demonstrated that both human-derived and murine-derived MSCs are able to improve outcomes in the animal model of MS, experimental autoimmune encephalomyelitis. How MSCs ameliorate experimental autoimmune encephalomyelitis is being intensely investigated. One of the major mechanisms of action of MSC therapy is to inhibit various components of the immune system that contribute to tissue destruction. Emerging evidence now supports the idea that MSCs can access the CNS where they can provide protection against tissue damage, and may facilitate tissue regeneration through the production of growth factors. The prospect of cell-based therapy using MSCs has several advantages, including the relative ease with which they can be extracted from autologous bone marrow or adipose tissue and expanded in vitro to reach the purity and numbers required for transplantation, and the fact that MSC therapy has already been used in other human disease settings, such as graft-versus-host and cardiac disease, with initial reports indicating a good safety profile. This article will focus on the theoretical and practical issues relevant to considerations of MSC therapy in the context of MS. PMID:21864075

Tissue engineering therapies for the vocal fold lamina propria.

PubMed

Kutty, Jaishankar K; Webb, Ken

2009-09-01

The vocal folds are laryngeal connective tissues with complex matrix composition/organization that provide the viscoelastic mechanical properties required for voice production. Vocal fold injury results in alterations in tissue structure and corresponding changes in tissue biomechanics that reduce vocal quality. Recent work has begun to elucidate the biochemical changes underlying injury-induced pathology and to apply tissue engineering principles to the prevention and reversal of vocal fold scarring. Based on the extensive history of injectable biomaterials in laryngeal surgery, a major focus of regenerative therapies has been the development of novel scaffolds with controlled in vivo residence time and viscoelastic properties approximating the native tissue. Additional strategies have included cell transplantation and delivery of the antifibrotic cytokine hepatocyte growth factor, as well as investigation of the effects of the unique vocal fold vibratory microenvironment using in vitro dynamic culture systems. Recent achievements of significant reductions in fibrosis and improved recovery of native tissue viscoelasticity and vibratory/functional performance in animal models are rapidly moving vocal fold tissue engineering toward clinical application.

Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

DTIC Science & Technology

2012-02-01

10-1-0927 TITLE: Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation...immunosuppression. Bone Marrow Derived Mesenchymal stem cells (BM-MSCs) are pluripotent cells, capable of differentiation along multiple mesenchymal lineages into...As part of implemented transition from University of Pittsburgh to Johns Hopkins University, we optimized our mesenchymal stem cell (MSC) isolation

Processing ultrasound backscatter to monitor high-intensity focused ultrasound (HIFU) therapy

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Anand, Ajay; Bailey, Michael R.

2005-09-01

The development of new noninvasive surgical methods such as HIFU for the treatment of cancer and internal bleeding requires simultaneous development of new sensing approaches to guide, monitor, and assess the therapy. Ultrasound imaging using echo amplitude has long been used to map tissue morphology for diagnostic interpretation by the clinician. New quantitative ultrasonic methods that rely on amplitude and phase processing for tissue characterization are being developed for monitoring of ablative therapy. We have been developing the use of full wave ultrasound backscattering for real-time temperature estimation, and to image changes in tissue backscatter spectrum as therapy progresses. Both approaches rely on differential processing of the backscatter signal in time, and precise measurement of phase differences. Noise and artifacts from motion and nonstationary speckle statistics are addressed by constraining inversions for tissue parameters with physical models. We present results of HIFU experiments with static point and scanned HIFU exposures in which temperature rise can be accurately mapped using a new heat transfer equation (HTE) model-constrained inverse approach. We also present results of a recently developed spectral imaging method that elucidates microbubble-mediated nonlinearity not visible as a change in backscatter amplitude. [Work supported by Army MRMC.

Accurate tumor localization and tracking in radiation therapy using wireless body sensor networks.

PubMed

Pourhomayoun, Mohammad; Jin, Zhanpeng; Fowler, Mark

2014-07-01

Radiation therapy is an effective method to combat cancerous tumors by killing the malignant cells or controlling their growth. Knowing the exact position of the tumor is a very critical prerequisite in radiation therapy. Since the position of the tumor changes during the process of radiation therapy due to the patient׳s movements and respiration, a real-time tumor tracking method is highly desirable in order to deliver a sufficient dose of radiation to the tumor region without damaging the surrounding healthy tissues. In this paper, we develop a novel tumor positioning method based on spatial sparsity. We estimate the position by processing the received signals from only one implantable RF transmitter. The proposed method uses less number of sensors compared to common magnetic transponder based approaches. The performance of the proposed method is evaluated in two different cases: (1) when the tissue configuration is perfectly determined (acquired beforehand by MRI or CT) and (2) when there are some uncertainties about the tissue boundaries. The results demonstrate the high accuracy and performance of the proposed method, even when the tissue boundaries are imperfectly known. Copyright © 2014 Elsevier Ltd. All rights reserved.

Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis.

PubMed

Sroussi, Herve Y; Epstein, Joel B; Bensadoun, Rene-Jean; Saunders, Deborah P; Lalla, Rajesh V; Migliorati, Cesar A; Heaivilin, Natalie; Zumsteg, Zachary S

2017-12-01

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chromophore absorbance change quantification in tissue during low-level light therapy

NASA Astrophysics Data System (ADS)

Huynh, Daniel; Chung, Christine; Qian, Li; Lilge, Lothar

2012-03-01

Low Level Light Therapy (LLLT) has been implicated to stimulate tissue, promoting healing and reducing pain. One of the potential pathways stimulated by LLLT relates to the electron transport chain, where photon quantum energy can induce a change in the biochemical reactions within the cell. The aim of this study is to assess the feasibility to exploit light additionally as a diagnostic tool to determine tissue physiological states, particularly in quantifying the changes in redox states of Cytochrome C as a result of induced LLLT biochemical reactions.

Advances in Meniscal Tissue Engineering

PubMed Central

Longo, Umile Giuseppe; Loppini, Mattia; Forriol, Francisco; Romeo, Giovanni; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Meniscal tears are the most common knee injuries and have a poor ability of healing. In the last few decades, several techniques have been increasingly used to optimize meniscal healing. Current research efforts of tissue engineering try to combine cell-based therapy, growth factors, gene therapy, and reabsorbable scaffolds to promote healing of meniscal defects. Preliminary studies did not allow to draw definitive conclusions on the use of these techniques for routine management of meniscal lesions. We performed a review of the available literature on current techniques of tissue engineering for the management of meniscal tears. PMID:25098366

Mitigation of eddy current heating during magnetic nanoparticle hyperthermia therapy.

PubMed

Stigliano, Robert V; Shubitidze, Fridon; Petryk, James D; Shoshiashvili, Levan; Petryk, Alicia A; Hoopes, P Jack

2016-11-01

Magnetic nanoparticle hyperthermia therapy is a promising technology for cancer treatment, involving delivering magnetic nanoparticles (MNPs) into tumours then activating them using an alternating magnetic field (AMF). The system produces not only a magnetic field, but also an electric field which penetrates normal tissue and induces eddy currents, resulting in unwanted heating of normal tissues. Magnitude of the eddy current depends, in part, on the AMF source and the size of the tissue exposed to the field. The majority of in vivo MNP hyperthermia therapy studies have been performed in small animals, which, due to the spatial distribution of the AMF relative to the size of the animals, do not reveal the potential toxicity of eddy current heating in larger tissues. This has posed a non-trivial challenge for researchers attempting to scale up to clinically relevant volumes of tissue. There is a relative dearth of studies focused on decreasing the maximum temperature resulting from eddy current heating to increase therapeutic ratio. This paper presents two simple, clinically applicable techniques for decreasing maximum temperature induced by eddy currents. Computational and experimental results are presented to understand the underlying physics of eddy currents induced in conducting, biological tissues and leverage these insights to mitigate eddy current heating during MNP hyperthermia therapy. Phantom studies show that the displacement and motion techniques reduce maximum temperature due to eddy currents by 74% and 19% in simulation, and by 77% and 33% experimentally. Further study is required to optimise these methods for particular scenarios; however, these results suggest larger volumes of tissue could be treated, and/or higher field strengths and frequencies could be used to attain increased MNP heating when these eddy current mitigation techniques are employed.

An end-to-end assessment of range uncertainty in proton therapy using animal tissues.

PubMed

Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

2016-11-21

Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams' superior dose advantage over conventional photon-based radiation therapy.

Design of optimal hyperthermia protocols for prostate cancer by controlling HSP expression through computer modeling (Invited Paper)

NASA Astrophysics Data System (ADS)

Rylander, Marissa N.; Feng, Yusheng; Diller, Kenneth; Bass, J.

2005-04-01

Heat shock proteins (HSP) are critical components of a complex defense mechanism essential for preserving cell survival under adverse environmental conditions. It is inevitable that hyperthermia will enhance tumor tissue viability, due to HSP expression in regions where temperatures are insufficient to coagulate proteins, and would likely increase the probability of cancer recurrence. Although hyperthermia therapy is commonly used in conjunction with radiotherapy, chemotherapy, and gene therapy to increase therapeutic effectiveness, the efficacy of these therapies can be substantially hindered due to HSP expression when hyperthermia is applied prior to these procedures. Therefore, in planning hyperthermia protocols, prediction of the HSP response of the tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of overall tissue response. In this paper, we present a highly accurate, adaptive, finite element tumor model capable of predicting the HSP expression distribution and tissue damage region based on measured cellular data when hyperthermia protocols are specified. Cubic spline representations of HSP27 and HSP70, and Arrhenius damage models were integrated into the finite element model to enable prediction of the HSP expression and damage distribution in the tissue following laser heating. Application of the model can enable optimized treatment planning by controlling of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

Flexible polymer waveguides for light-activated therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kim, Moonseok; Kwok, Sheldon J. J.; Lin, Harvey H.; Lee, Dong Hee; Yun, Seok Hyun

2017-02-01

Conventional light-activated therapies, such as photodynamic therapy (PDT), photochemical tissue bonding (PTB), collagen crosslinking (CXL), low-level light therapy (LLLT), and antimicrobial therapy utilize external light sources and light propagation through free space, limiting treatment to accessible and superficial areas of the body. Recent progress has been made in developing biocompatible polymer waveguides to enhance light delivery to deep tissues. To further expand clinical utility, waveguides should be flexible and tough enough to enable use in anatomically difficult-to-reach regions, while having the requisite optical properties to achieve uniform and efficient illumination of the target area. Here, we present a new class of flexible polymer waveguides optimized for uniform light extraction into tissues. Our slab waveguides comprise two designs: first, a flexible polydimethylsiloxane (PDMS) based elastomer for CXL, and second, a tough polyacrylamide and alginate hydrogel for large-area phototherapies. Our waveguides are optically transparent in the visible wavelengths (400-750 nm) and a multimode fiber is used to couple light into the waveguide. We characterized the light propagation through the waveguides and light extraction into tissue, and validated our results with optical simulation. By changing the thickness and scattering properties, uniform light extraction through the length of the waveguide could be achieved. We demonstrate proof-of-concept scleral photo-crosslinking of an ex vivo porcine eyeball for prevention of myopia.

Atmospheric Pressure Photoionization Tandem Mass Spectrometry of Androgens in Prostate Cancer

PubMed Central

Lih, Fred Bjørn; Titus, Mark A.; Mohler, James L.; Tomer, Kenneth B.

2010-01-01

Androgen deprivation therapy is the most common treatment option for advanced prostate cancer. Almost all prostate cancers recur during androgen deprivation therapy, and new evidence suggests that androgen receptor activation persists despite castrate levels of circulating androgens. Quantitation of tissue levels of androgens is critical to understanding the mechanism of recurrence of prostate cancer during androgen deprivation therapy. A liquid chromatography atmospheric pressure photoionization tandem mass spectrometric method was developed for quantitation of tissue levels of androgens. Quantitation of the saturated keto-steroids dihydrotestosterone and 5-α-androstanedione required detection of a novel parent ion, [M + 15]+. The nature of this parent ion was explored and the method applied to prostate tissue and cell culture with comparison to results achieved using electrospray ionization. PMID:20560527

Progress on materials and scaffold fabrications applied to esophageal tissue engineering.

PubMed

Shen, Qiuxiang; Shi, Peina; Gao, Mongna; Yu, Xuechan; Liu, Yuxin; Luo, Ling; Zhu, Yabin

2013-05-01

The mortality rate from esophageal disease like atresia, carcinoma, tracheoesophageal fistula, etc. is increasing rapidly all over the world. Traditional therapies such as surgery, radiotherapy or chemotherapy have been met with very limited success resulting in reduced survival rate and quality of patients' life. Tissue-engineered esophagus, a novel substitute possessing structure and function similar to native tissue, is believed to be an effective therapy and a promising replacement in the future. However, research on esophageal tissue engineering is still at an early stage. Considerable research has been focused on developing ideal scaffolds with optimal materials and methods of fabrication. This article gives a review of materials and scaffold fabrications currently applied in esophageal tissue engineering research. Copyright © 2013 Elsevier B.V. All rights reserved.

Shedding Light on Nanomedicine

PubMed Central

Tong, Rong

2012-01-01

Light is electromagnetic radiation that can convert its energy into different forms (e.g., heat, chemical energy, and acoustic waves). This property has been exploited in phototherapy (e.g., photothermal therapy and photodynamic therapy) and optical imaging (e.g., fluorescence imaging) for therapeutic and diagnostic purposes. Light-controlled therapies can provide minimally or non-invasive spatiotemporal control as well as deep tissue penetration. Nanotechnology provides a numerous advantages, including selective targeting of tissues, prolongation of therapeutic effect, protection of active payloads, and improved therapeutic indices. This review explores the advances that nanotechnology can bring to light-based therapies and diagnostics, and vice versa, including photo-triggered systems, nanoparticles containing photoactive molecules, and nanoparticles that are themselves photoactive. Limitations of light-based therapies such as photic injury and phototoxicity will be discussed. PMID:22887840

Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy.

PubMed

Paul, Anup; Narasimhan, Arunn; Das, Sarit K; Sengupta, Soujit; Pradeep, Thalappil

2016-11-01

The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 °C for bare tissue, it was 19 °C for tissue embedded with gold nanostructures and 38 °C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided.

Advanced therapies for the treatment of hemophilia: future perspectives.

PubMed

Liras, Antonio; Segovia, Cristina; Gabán, Aline S

2012-12-13

Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression.

Regenerative periodontal therapy in mucogingival surgery for root coverage.

PubMed

Abitbol, T; Santi, E; Urbani, G

1997-02-01

This article illustrates the potential benefits of regenerative periodontal therapy in mucogingival surgery and esthetic dental treatment. Cases are described in which the treatment of soft-tissue recessions and root exposures are treated with surgical procedures where both clinical soft-tissue augmentation and the regeneration of periodontal attachment are obtained. Cases are also presented to illustrate the clinical application of guided tissue regeneration. Resorbable and nonresorbable barriers are placed over the root surface and bone and covered by the overlying flap, which allows the selective repopulation of the lesion by progenitor cells and the inhibition of a long junctional epithelium. Emphasis is placed on regenerative procedures in soft-tissue augmentation, particularly with respect to rationales, techniques, and indications.

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings.

PubMed

Law, T T; Tong, Daniel; Wong, Sam W H; Chan, S Y; Law, Simon

2015-04-01

Gastric mucosa-associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pylori-eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosa-associated lymphoid tissue lymphoma and its management are reviewed.

Clinical Translation of Cell Therapy, Tissue Engineering, and Regenerative Medicine Product in Malaysia and Its Regulatory Policy.

PubMed

Bt Hj Idrus, Ruszymah; Abas, Arpah; Ab Rahim, Fazillahnor; Saim, Aminuddin Bin

2015-12-01

With the worldwide growth of cell and tissue therapy (CTT) in treating diseases, the need of a standardized regulatory policy is of paramount concern. Research in CTT in Malaysia has reached stages of clinical trials and commercialization. In Malaysia, the regulation of CTT is under the purview of the National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH). NPCB is given the task of regulating CTT, under a new Cell and Gene Therapy Products framework, and the guidelines are currently being formulated. Apart from the laboratory accreditation, researchers are advised to follow Guidelines for Stem Cell Research and Therapy from the Medical Development Division, MOH, published in 2009.

Clinical Translation of Cell Therapy, Tissue Engineering, and Regenerative Medicine Product in Malaysia and Its Regulatory Policy

PubMed Central

Abas, Arpah; Ab Rahim, Fazillahnor; Saim, Aminuddin Bin

2015-01-01

With the worldwide growth of cell and tissue therapy (CTT) in treating diseases, the need of a standardized regulatory policy is of paramount concern. Research in CTT in Malaysia has reached stages of clinical trials and commercialization. In Malaysia, the regulation of CTT is under the purview of the National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH). NPCB is given the task of regulating CTT, under a new Cell and Gene Therapy Products framework, and the guidelines are currently being formulated. Apart from the laboratory accreditation, researchers are advised to follow Guidelines for Stem Cell Research and Therapy from the Medical Development Division, MOH, published in 2009. PMID:26192075

Engineering organs.

PubMed

Atala, Anthony

2009-10-01

Applications of regenerative medicine technology may offer novel therapies for patients with injuries, end-stage organ failure, or other clinical problems. Currently, patients suffering from diseased and injured organs can be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new avenues for this type of therapy. For example, therapeutic cloning and cellular reprogramming may one day provide a potentially limitless source of cells for tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors have already entered the clinical setting successfully, indicating the promise regenerative medicine holds for the future.

Using Acellular Bioactive Extracellular Matrix Scaffolds to Enhance Endogenous Cardiac Repair

PubMed Central

Svystonyuk, Daniyil A.; Mewhort, Holly E. M.; Fedak, Paul W. M.

2018-01-01

An inability to recover lost cardiac muscle following acute ischemic injury remains the biggest shortcoming of current therapies to prevent heart failure. As compared to standard medical and surgical treatments, tissue engineering strategies offer the promise of improved heart function by inducing regeneration of functional heart muscle. Tissue engineering approaches that use stem cells and genetic manipulation have shown promise in preclinical studies but have also been challenged by numerous critical barriers preventing effective clinical translational. We believe that surgical intervention using acellular bioactive ECM scaffolds may yield similar therapeutic benefits with minimal translational hurdles. In this review, we outline the limitations of cellular-based tissue engineering strategies and the advantages of using acellular biomaterials with bioinductive properties. We highlight key anatomic targets enriched with cellular niches that can be uniquely activated using bioactive scaffold therapy. Finally, we review the evolving cardiovascular tissue engineering landscape and provide critical insights into the potential therapeutic benefits of acellular scaffold therapy. PMID:29696148

Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy.

PubMed

Salehi, Samie; Saljooghi, Amir Sh; Badiee, Somayeh; Moqadam, Mojtaba Mashmool

2017-10-01

Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days. It was hypothesized that the two chelators might be more efficient as a combined therapy than as monotherapies in removing thallium (III) from the rats' organs. The chelators were administered orally as either single or combined therapies for a period of 14 days. Serum and tissue thallium (III) and iron concentrations were determined by flame atomic absorption spectroscopy. Serum and tissue thallium (III) levels were significantly reduced by combined therapy with DFX and L1. Additionally, iron concentrations returned to normal levels and symptoms of toxicity decreased.

Management of Facial Pyoderma Gangrenosum Using Platelet-Rich Fibrin: A Technical Report.

PubMed

Fortunato, Leonzio; Barone, Selene; Bennardo, Francesco; Giudice, Amerigo

2018-01-31

This report describes a case of local pyoderma gangrenosum that was treated with short-term immunosuppressive therapy and the topical application of platelet-rich fibrin (PRF). Medical treatment included oral corticosteroid therapy and topical treatment with PRF in solid and liquid form. This therapy initially led to the reduction of the ulcer's size and an improvement in symptoms, until the ulcer was completely healed after a few weeks. A relapse was treated with only the application of PRF to the affected tissue with excellent recovery. The efficacy of PRF as a guide for wound healing is a result of the continuous release of growth factors involved in tissue repair mechanisms. PRF has proved to be suitable for the management of facial pyoderma gangrenosum while allowing a reduction in systemic corticosteroid therapy. The ease of preparation, low cost, and outpatient use make PRF an optimal scaffold for tissue healing processes. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Boronated porhyrins and methods for their use

DOEpatents

Miura, Michiko; Shelnutt, John A.; Slatkin, Daniel N.

1999-03-02

The present invention covers boronated porphyrins containing multiple carborane cages which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies such as boron neutron capture therapy and photodynamic therapy.

Rational Autologous Cell Sources For Therapy of Heart Failure - Vehicles and Targets For Gene and RNA Therapies.

PubMed

Lampinen, Milla; Vento, Antti; Laurikka, Jari; Nystedt, Johanna; Mervaala, Eero; Harjula, Ari; Kankuri, Esko

2016-01-01

This review focuses on the possibilities for intraoperative processing and isolation of autologous cells, particularly atrial appendage-derived cells (AADCs) and cellular micrografts, and their straightforward use in cell transplantation for heart failure therapy. We review the potential of autologous tissues to serve as sources for cell therapy and consider especially those tissues that are used in surgery but from which the excess is currently discarded as surgical waste. We compare the inculture expanded cells to the freshly isolated ones in terms of evidence-based cost-efficacy and their usability as gene- and RNA therapy vehicles. We also review how financial and authority-based decisions and restrictions sculpt the landscape for patients to participate in academic-based trials. Finally, we provide an insight example into AADCs isolation and processing for epicardial therapy during coronary artery bypass surgery.

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.

PubMed Central

Lilge, L.; Olivo, M. C.; Schatz, S. W.; MaGuire, J. A.; Patterson, M. S.; Wilson, B. C.

1996-01-01

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8562339

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

PubMed Central

Gay, Hiram A.; Barthold, H. Joseph; O’Meara, Elizabeth; Bosch, Walter R.; El Naqa, Issam; Al-Lozi, Rawan; Rosenthal, Seth A.; Lawton, Colleen; Lee, W. Robert; Sandler, Howard; Zietman, Anthony; Myerson, Robert; Dawson, Laura A.; Willett, Christopher; Kachnic, Lisa A.; Jhingran, Anuja; Portelance, Lorraine; Ryu, Janice; Small, William; Gaffney, David; Viswanathan, Akila N.; Michalski, Jeff M.

2012-01-01

Purpose To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research. PMID:22483697

Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism.

PubMed

Jankowski, Marek; Gawrych, Mariusz; Adamska, Urszula; Ciescinski, Jakub; Serafin, Zbigniew; Czajkowski, Rafal

2017-02-01

Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects' abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient's skin.

Clinical translation of photobiomodulation therapy using evidences from precision molecular pathway analyses (Conference Presentation)

NASA Astrophysics Data System (ADS)

Arany, Praveen

2017-02-01

Can `light' be a Drug? To satisfy this definition as a pharmaceutical agent, light must be absorbed and change bodily function. Much evidence from our understanding of our visual cycle and Vitamin D metabolism have all noted this phenomenon. Advances in optophotonic technologies along with a better understanding of light-tissue interactions, especially in in vivo optical imaging and optogenetics, are spearheading the popularity of biophotonics in biology and medicine. The use of lasers and light devices at high doses in dermatology, ophthalmology, oncology and dentistry are now considered mainstream for certain clinical applications such as surgery, skin rejuvenation, ocular and soft tissue recontouring, anti-tumor and anti-microbial photodynamic therapy. In contrast, therapeutic use of low dose biophotonics devices is called Low Level Light / Laser Therapy (LLLT), now termed Photobiomodulation (PBM) Therapy. This therapy is defined as a non-thermal use of non-ionizing forms of electromagnetic radiation to alleviate pain, inflammation, modulating the immune responses and promoting wound healing and tissue regeneration. Surprisingly, despite vast volumes of scientific literature from both clinical and laboratory studies noting the phenomenological evidences for this innovative therapy, limited mechanistic insights have prevented the development of rigorous, reproducible clinical protocols. This presentation will outline our current efforts at ongoing efforts in our group to assess molecular pathways and precisely define clinical treatment variables to enable clinical translation with PBM therapies.

SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte Carlo Simulation and Experimental Study Using Animal Tissue Phantoms.

PubMed

Liu, Y; Zheng, Y

2012-06-01

Accurate determination of proton dosimetric effect for tissue heterogeneity is critical in proton therapy. Proton beams have finite range and consequently tissue heterogeneity plays a more critical role in proton therapy. The purpose of this study is to investigate the tissue heterogeneity effect in proton dosimetry based on anatomical-based Monte Carlo simulation using animal tissues. Animal tissues including a pig head and beef bulk were used in this study. Both pig head and beef were scanned using a GE CT scanner with 1.25 mm slice thickness. A treatment plan was created, using the CMS XiO treatment planning system (TPS) with a single proton spread-out-Bragg-peak beam (SOBP). Radiochromic films were placed at the distal falloff region. Image guidance was used to align the phantom before proton beams were delivered according to the treatment plan. The same two CT sets were converted to Monte Carlo simulation model. The Monte Carlo simulated dose calculations with/without tissue omposition were compared to TPS calculations and measurements. Based on the preliminary comparison, at the center of SOBP plane, the Monte Carlo simulation dose without tissue composition agreed generally well with TPS calculation. In the distal falloff region, the dose difference was large, and about 2 mm isodose line shift was observed with the consideration of tissue composition. The detailed comparison of dose distributions between Monte Carlo simulation, TPS calculations and measurements is underway. Accurate proton dose calculations are challenging in proton treatment planning for heterogeneous tissues. Tissue heterogeneity and tissue composition may lead to isodose line shifts up to a few millimeters in the distal falloff region. By simulating detailed particle transport and energy deposition, Monte Carlo simulations provide a verification method in proton dose calculation where inhomogeneous tissues are present. © 2012 American Association of Physicists in Medicine.

Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

ClinicalTrials.gov

2017-06-27

Adult Malignant Mesenchymoma; Adult Rhabdomyosarcoma; Childhood Alveolar Rhabdomyosarcoma; Childhood Botryoid-Type Embryonal Rhabdomyosarcoma; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Mesenchymoma; Non-Metastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity

DTIC Science & Technology

2009-07-01

27] Ross S, Spencer SD, Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo...Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate

Limb Blood Flow After Class 4 Laser Therapy

PubMed Central

Larkin, Kelly A.; Martin, Jeffrey S.; Zeanah, Elizabeth H.; True, Jerry M.; Braith, Randy W.; Borsa, Paul A.

2012-01-01

Context: Laser therapy is purported to improve blood flow in soft tissues. Modulating circulation would promote healing by controlling postinjury ischemia, hypoxia, edema, and secondary tissue damage. However, no studies have quantified these responses to laser therapy. Objective: To determine a therapeutic dose range for laser therapy for increasing blood flow to the forearm. Design: Crossover study. Setting: Controlled laboratory setting. Patients or Other Participants: Ten healthy, college-aged men (age = 20.80 ± 2.16 years, height = 177.93 ± 3.38 cm, weight = 73.64 ± 9.10 kg) with no current history of injury to the upper extremity or cardiovascular conditions. Intervention(s): A class 4 laser device was used to treat the biceps brachii muscle. Each grid point was treated for 3 to 4 seconds, for a total of 4 minutes. Each participant received 4 doses of laser therapy: sham, 1 W, 3 W, and 6 W. Main Outcome Measure(s): The dependent variables were changes in blood flow, measured using venous occlusion plethysmography. We used a repeated-measures analysis of variance to analyze changes in blood flow for each dose at 2, 3, and 4 minutes and at 1, 2, 3, 4, and 5 minutes after treatment. The Huynh-Feldt test was conducted to examine differences over time. Results: Compared with baseline, blood flow increased over time with the 3-W treatment (F3,9 = 3.468, P < .011) at minute 4 of treatment (2.417 ± 0.342 versus 2.794 ± 0.351 mL/min per 100 mL tissue, P = .032), and at 1 minute (2.767 ± 0.358 mL/min per 100 mL tissue, P < .01) and 2 minutes (2.657 ± 0.369 mL/min per 100 mL tissue, P = .022) after treatment. The sham, 1-W, and 6-W treatment doses did not change blood flow from baseline at any time point. Conclusions: Laser therapy at the 3-W (360-J) dose level was an effective treatment modality to increase blood flow in the soft tissues. PMID:22488283

Protein-anchoring therapy to target extracellular matrix proteins to their physiological destinations.

PubMed

Ito, Mikako; Ohno, Kinji

2018-02-20

Endplate acetylcholinesterase (AChE) deficiency is a form of congenital myasthenic syndrome (CMS) caused by mutations in COLQ, which encodes collagen Q (ColQ). ColQ is an extracellular matrix (ECM) protein that anchors AChE to the synaptic basal lamina. Biglycan, encoded by BGN, is another ECM protein that binds to the dystrophin-associated protein complex (DAPC) on skeletal muscle, which links the actin cytoskeleton and ECM proteins to stabilize the sarcolemma during repeated muscle contractions. Upregulation of biglycan stabilizes the DPAC. Gene therapy can potentially ameliorate any disease that can be recapitulated in cultured cells. However, the difficulty of tissue-specific and developmental stage-specific regulated expression of transgenes, as well as the difficulty of introducing a transgene into all cells in a specific tissue, prevents us from successfully applying gene therapy to many human diseases. In contrast to intracellular proteins, an ECM protein is anchored to the target tissue via its specific binding affinity for protein(s) expressed on the cell surface within the target tissue. Exploiting this unique feature of ECM proteins, we developed protein-anchoring therapy in which a transgene product expressed even in remote tissues can be delivered and anchored to a target tissue using specific binding signals. We demonstrate the application of protein-anchoring therapy to two disease models. First, intravenous administration of adeno-associated virus (AAV) serotype 8-COLQ to Colq-deficient mice, resulting in specific anchoring of ectopically expressed ColQ-AChE at the NMJ, markedly improved motor functions, synaptic transmission, and the ultrastructure of the neuromuscular junction (NMJ). In the second example, Mdx mice, a model for Duchenne muscular dystrophy, were intravenously injected with AAV8-BGN. The treatment ameliorated motor deficits, mitigated muscle histopathologies, decreased plasma creatine kinase activities, and upregulated expression of utrophin and DAPC component proteins. We propose that protein-anchoring therapy could be applied to hereditary/acquired defects in ECM and secreted proteins, as well as therapeutic overexpression of such factors. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer

PubMed Central

Rose, Rebecca; Lamers, Susanna L.; Nolan, David J.; Maidji, Ekaterina; Faria, N. R.; Pybus, Oliver G.; Dollar, James J.; Maruniak, Samuel A.; McAvoy, Andrew C.; Salemi, Marco; Stoddart, Cheryl A.; Singer, Elyse J.

2016-01-01

ABSTRACT While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV+ cART-treated (cART+) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART+ and cART-naive (cART−) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA+ cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. IMPORTANCE Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV+ cART+ individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies. PMID:27466425

HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

PubMed

Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

2016-10-15

While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV(+) cART(+) individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Comparison of histopathology and real-time polymerase chain reaction (RT-PCR) for detection of Mycobacterium tuberculosis in fistula-in-ano.

PubMed

Garg, Pankaj

2017-07-01

Histopathology is commonly used to diagnose tuberculosis in fistula-in-ano. The aim was to compare the sensitivity of polymerase chain reaction and histopathology in detecting tuberculosis in fistula-in-ano. The histopathology and polymerase chain-reaction of tissue (fistula tract) was done in all the consecutive operated cases. When pus sample was also available, polymerase chain reaction-pus was also done RESULTS: Three hundred forty seven samples (179 patients) were tested over 2 years (median 6.5 months). The mean age was 38.8 ± 10.7 years, and male/female was 170/9. Histopathology and polymerase chain reaction of tissue (fistula tract) was done in 152 and 165 patients, respectively. Polymerase chain reaction (pus) could be done in 30 patients. Overall, tuberculosis was detected in 20/179 (11.2%) patients. Of these, tuberculosis was detected by histopathology (tissue) in 1/152 (0.7%) and by polymerase chain reaction (tissue) in 14/165 (8.5%) patients. In pus, polymerase chain reaction detected tuberculosis in 6/30 (20%) patients. Both polymerase chain reaction of tissue and pus were positive in one patient. Polymerase chain reaction (tissue) and polymerase chain reaction (pus) were significantly more sensitive than histopathology (tissue) for detecting tuberculosis [histopathology 1/152 vs. polymerase chain reaction (tissue) 14/165, p = 0.0009] [histopathology 1/152 vs. polymerase chain reaction (pus) 6/30, p < 0.0001]. In 20 patients detected to have tuberculosis, four drug anti-tubercular therapy was recommended for 6 months. The therapy was completed in 13 patients and 12/13 (92.3%) were cured. The therapy is continuing in 3/20 patients. Four patients did not take the therapy. None of them was cured. Polymerase chain reaction was significantly more sensitive than histopathology in detecting tuberculosis in fistula-in-ano. Histopathology might be missing out tuberculosis in many patients leading to recurrence of the fistula.

Preliminary Evaluation of Platelet Rich Fibrin-Mediated Tissue Repair in Immature Canine Pulpless Teeth.

PubMed

Wang, Qi Lin; Yang, Pan Pan; Ge, Li Hong; Liu, He

2016-03-01

To evaluate the use of platelet-rich fibrin (PRF) in the regenerative therapy of immature canine permanent teeth. Eight immature premolars of beagle dogs were pulp extracted and cleaned with irrigation, then divided into two groups of empty root canals and those filled with a PRF clot. All of the eight premolars were sealed with mineral trioxide aggregate and glass ionomer cement. Two premolars were left naturally grown as a positive control. The root development was assessed radiographically and histologically after 12 weeks. The radiological findings showed greater increases in the thickness of lateral dentinal wall in the PRF group than in the vacant group. Histologically, dental-associated mineral tissue, connective tissue, and bone-like mineral tissue grew into the root canals independent of PRF clot use. The PRF was able to increase the thickness of dental-associated mineral tissue. However, the vital tissue differed from the pulp dentin complex. Our study demonstrated the feasibility of using PRF-mediated regenerative therapy in pulpless immature teeth for improving tissue repair.

Stromal cells in tissue homeostasis: balancing regeneration and fibrosis.

PubMed

Rabelink, Ton J; Little, Melissa H

2013-12-01

The ageing population and the increasing prevalence of noncommunicable diseases such as diabetes and hypertension have led to an increased prevalence of chronic kidney disease. The generation of de novo kidney tissue from embryonic tissue and stem cells using tissue engineering approaches is being explored as an alternative to renal replacement therapy for treating the disease. It is, however, becoming clear that resident cells can not only induce fibrotic repair, but can also restore damaged kidney tissue. Mobilizing this innate capacity of the kidney to regenerate is of particular interest in the prevention of irreversible kidney failure. A novel concept is that the interaction of interstitial stromal cells with the local immune system may regulate tissue homeostasis and the balance between tissue repair and fibrosis. Mesenchymal stromal cells (MSCs), in particular, may enhance the intrinsic reparative capabilities of the kidney. This Perspectives article considers the innate regenerative potential of the kidney in the context of ongoing studies of MSC therapy.

Boronated porhyrins and methods for their use

DOEpatents

Miura, M.; Shelnutt, J.A.; Slatkin, D.N.

1999-03-02

The present invention covers boronated porphyrins containing multiple carborane cages which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies such as boron neutron capture therapy and photodynamic therapy. 3 figs.

Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy

PubMed Central

Javan, Bita; Shahbazi, Majid

2017-01-01

Transcriptional targeting is the best approach for specific gene therapy. Hypoxia is a common feature of the tumour microenvironment. Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. However, this system needs to be optimised to have maximum efficacy with minimum side effects in normal tissues. The combination of tissue-/tumour-specific promoters with HRE core sequences has been found to enhance the specificity and efficacy of this system. In this review, hypoxia-inducible gene expression system as well as gene therapy strategies targeting tumour hypoxia will be discussed. This review will also focus on hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation systems developed for cancer-specific gene therapy. PMID:28798809

Monte-Carlo based assessment of MAGIC, MAGICAUG, PAGATUG and PAGATAUG polymer gel dosimeters for ovaries and uterus organ dosimetry in brachytherapy, nuclear medicine and Tele-therapy.

PubMed

Adinehvand, Karim; Rahatabad, Fereidoun Nowshiravan

2018-06-01

Calculation of 3D dose distribution during radiotherapy and nuclear medicine helps us for better treatment of sensitive organs such as ovaries and uterus. In this research, we investigate two groups of normoxic dosimeters based on meta-acrylic acid (MAGIC and MAGICAUG) and polyacrylamide (PAGATUG and PAGATAUG) for brachytherapy, nuclear medicine and Tele-therapy in their sensitive and critical role as organ dosimeters. These polymer gel dosimeters are compared with soft tissue while irradiated by different energy photons in therapeutic applications. This comparison has been simulated by Monte-Carlo based MCNPX code. ORNL phantom-Female has been used to model the critical organs of kidneys, ovaries and uterus. Right kidney is proposed to be the source of irradiation and another two organs are exposed to this irradiation. Effective atomic numbers of soft tissue, MAGIC, MAGICAUG, PAGATUG and PAGATAUG are 6.86, 7.07, 6.95, 7.28, and 7.07 respectively. Results show the polymer gel dosimeters are comparable to soft tissue for using in nuclear medicine and Tele-therapy. Differences between gel dosimeters and soft tissue are defined as the dose responses. This difference is less than 4.1%, 22.6% and 71.9% for Tele-therapy, nuclear medicine and brachytherapy respectively. The results approved that gel dosimeters are the best choice for ovaries and uterus in nuclear medicine and Tele-therapy respectively. Due to the slight difference between the effective atomic numbers of these polymer gel dosimeters and soft tissue, these polymer gels are not suitable for brachytherapy since the dependence of photon interaction to atomic number, for low energy brachytherapy, had been so effective. Also this dependence to atomic number, decrease for photoelectric and increase for Compton. Therefore polymer gel dosimeters are not a good alternative to soft tissue replacement in brachytherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Customized biomaterials to augment chondrocyte gene therapy.

PubMed

Aguilar, Izath Nizeet; Trippel, Stephen; Shi, Shuiliang; Bonassar, Lawrence J

2017-04-15

A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor-I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins. The present manuscript focuses on the enhancement of chondrocyte gene therapy through the modification of scaffold materials to enhance the retention of targeted gene products. This study combined tissue engineering and gene therapy, where customized biomaterials augmented the action of IGF-I by enhancing the retention of protein produced by transfection of the IGF-I gene. This approach enabled tuning of binding of IGF-I to alginate, which increased GAG and HYPRO production by transfected chondrocytes. To our knowledge, peptide-based modification of materials to augment growth factor-targeted gene therapy has not been reported previously. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Imaging feedback for histotripsy by characterizing dynamics of acoustic radiation force impulse (ARFI)-induced shear waves excited in a treated volume.

PubMed

Wang, Tzu-Yin; Hall, Timothy L; Xu, Zhen; Fowlkes, J Brian; Cain, Charles A

2014-07-01

Our previous study indicated that shear waves decay and propagate at a lower speed as they propagate into a tissue volume mechanically fractionated by histotripsy. In this paper, we hypothesize that the change in the shear dynamics is related to the degree of tissue fractionation, and can be used to predict histotripsy treatment outcomes. To test this hypothesis, lesions with different degrees of tissue fractionation were created in agar-graphite tissue phantoms and ex vivo kidneys with increasing numbers of therapy pulses, from 0 to 2000 pulses per treatment location. The therapy pulses were 3-cycle 750-kHz focused ultrasound delivered at a peak negative/positive pressure of 17/108 MPa and a repetition rate of 50 Hz. The shear waves were excited by acoustic radiation force impulse (ARFI) focused at the center of the lesion. The spatial and temporal behavior of the propagating shear waves was measured with ultrasound plane wave imaging. The temporal displacement profile at a lateral location 10 mm offset to the shear excitation region was detected with M-mode imaging. The decay and delay of the shear waves were quantitatively characterized on the temporal displacement profile. Results showed significant changes in two characteristics on the temporal displacement profile: the peak-to-peak displacement decayed exponentially with increasing numbers of therapy pulses; the relative time-to-peak displacement increased with increasing numbers of therapy pulses, and appeared to saturate at higher numbers of pulses. Correspondingly, the degree of tissues fractionation, as indicated by the percentage of structurally intact cell nuclei, decreased exponentially with increasing numbers of therapy pulses. Strong linear correlations were found between the two characteristics and the degree of tissue fractionation. These results suggest that the characteristics of the shear temporal displacement profile may provide useful feedback information regarding the treatment outcomes.

A Numerical Investigation of the Electric and Thermal Cell Kill Distributions in Electroporation-Based Therapies in Tissue

PubMed Central

Garcia, Paulo A.; Davalos, Rafael V.; Miklavcic, Damijan

2014-01-01

Electroporation-based therapies are powerful biotechnological tools for enhancing the delivery of exogeneous agents or killing tissue with pulsed electric fields (PEFs). Electrochemotherapy (ECT) and gene therapy based on gene electrotransfer (EGT) both use reversible electroporation to deliver chemotherapeutics or plasmid DNA into cells, respectively. In both ECT and EGT, the goal is to permeabilize the cell membrane while maintaining high cell viability in order to facilitate drug or gene transport into the cell cytoplasm and induce a therapeutic response. Irreversible electroporation (IRE) results in cell kill due to exposure to PEFs without drugs and is under clinical evaluation for treating otherwise unresectable tumors. These PEF therapies rely mainly on the electric field distributions and do not require changes in tissue temperature for their effectiveness. However, in immediate vicinity of the electrodes the treatment may results in cell kill due to thermal damage because of the inhomogeneous electric field distribution and high current density during the electroporation-based therapies. Therefore, the main objective of this numerical study is to evaluate the influence of pulse number and electrical conductivity in the predicted cell kill zone due to irreversible electroporation and thermal damage. Specifically, we simulated a typical IRE protocol that employs ninety 100-µs PEFs. Our results confirm that it is possible to achieve predominant cell kill due to electroporation if the PEF parameters are chosen carefully. However, if either the pulse number and/or the tissue conductivity are too high, there is also potential to achieve cell kill due to thermal damage in the immediate vicinity of the electrodes. Therefore, it is critical for physicians to be mindful of placement of electrodes with respect to critical tissue structures and treatment parameters in order to maintain the non-thermal benefits of electroporation and prevent unnecessary damage to surrounding healthy tissue, critical vascular structures, and/or adjacent organs. PMID:25115970

Stem cells as a novel tool for drug screening and treatment of degenerative diseases.

PubMed

Zuba-Surma, Ewa K; Wojakowski, Wojciech; Madeja, Zbigniew; Ratajczak, Mariusz Z

2012-01-01

Degenerative diseases similarly as acute tissue injuries lead to massive cell loss and may cause organ failure of vital organs (e.g., heart, central nervous system). Therefore, they belong to a group of disorders that may significantly benefit from stem cells (SCs)-based therapies. Several stem and progenitor cell populations have already been described as valuable tools for developing therapeutic strategies in regenerative medicine. In particular, pluripotent stem cells (PSCs), including adult-tissue-derived PSCs, neonatal-tissue-derived SCs, embryonic stem cells (ESCs), and recently described induced pluripotent stem cells (iPSCs), are the focus of particular attention because of their capacity to differentiate into all the cell lineages. Although PSCs are predominantly envisioned to be applied for organ regeneration, they may be also successfully employed in drug screening and disease modeling. In particular, adult PSCs and iPSCs derived from patient tissues may not only be a source of cells for autologous therapies but also for individual customized in vitro drug testing and studies on the molecular mechanisms of disease. In this review, we will focus on the potential applications of SCs, especially PSCs i) in regenerative medicine therapies, ii) in studying mechanisms of disease, as well as iii) in drug screening and toxicology tests that are crucial in new drug development. In particular, we will discuss the application of SCs in developing new therapeutic approaches to treat degenerative diseases of the neural system and heart. The advantage of adult PSCs in all the above-mentioned settings is that they can be directly harvested from patient tissues and used not only as a safe non-immunogenic source of cells for therapy but also as tools for personalized drug screening and pharmacological therapies.

Modeling of electric field distribution in tissues during electroporation

PubMed Central

2013-01-01

Background Electroporation based therapies and treatments (e.g. electrochemotherapy, gene electrotransfer for gene therapy and DNA vaccination, tissue ablation with irreversible electroporation and transdermal drug delivery) require a precise prediction of the therapy or treatment outcome by a personalized treatment planning procedure. Numerical modeling of local electric field distribution within electroporated tissues has become an important tool in treatment planning procedure in both clinical and experimental settings. Recent studies have reported that the uncertainties in electrical properties (i.e. electric conductivity of the treated tissues and the rate of increase in electric conductivity due to electroporation) predefined in numerical models have large effect on electroporation based therapy and treatment effectiveness. The aim of our study was to investigate whether the increase in electric conductivity of tissues needs to be taken into account when modeling tissue response to the electroporation pulses and how it affects the local electric distribution within electroporated tissues. Methods We built 3D numerical models for single tissue (one type of tissue, e.g. liver) and composite tissue (several types of tissues, e.g. subcutaneous tumor). Our computer simulations were performed by using three different modeling approaches that are based on finite element method: inverse analysis, nonlinear parametric and sequential analysis. We compared linear (i.e. tissue conductivity is constant) model and non-linear (i.e. tissue conductivity is electric field dependent) model. By calculating goodness of fit measure we compared the results of our numerical simulations to the results of in vivo measurements. Results The results of our study show that the nonlinear models (i.e. tissue conductivity is electric field dependent: σ(E)) fit experimental data better than linear models (i.e. tissue conductivity is constant). This was found for both single tissue and composite tissue. Our results of electric field distribution modeling in linear model of composite tissue (i.e. in the subcutaneous tumor model that do not take into account the relationship σ(E)) showed that a very high electric field (above irreversible threshold value) was concentrated only in the stratum corneum while the target tumor tissue was not successfully treated. Furthermore, the calculated volume of the target tumor tissue exposed to the electric field above reversible threshold in the subcutaneous model was zero assuming constant conductivities of each tissue. Our results also show that the inverse analysis allows for identification of both baseline tissue conductivity (i.e. conductivity of non-electroporated tissue) and tissue conductivity vs. electric field (σ(E)) of electroporated tissue. Conclusion Our results of modeling of electric field distribution in tissues during electroporation show that the changes in electrical conductivity due to electroporation need to be taken into account when an electroporation based treatment is planned or investigated. We concluded that the model of electric field distribution that takes into account the increase in electric conductivity due to electroporation yields more precise prediction of successfully electroporated target tissue volume. The findings of our study can significantly contribute to the current development of individualized patient-specific electroporation based treatment planning. PMID:23433433

Unique Diagnostic and Therapeutic Roles of Porphyrins and Phthalocyanines in Photodynamic Therapy, Imaging and Theranostics

PubMed Central

Josefsen, Leanne B.; Boyle, Ross W.

2012-01-01

Porphyrinic molecules have a unique theranostic role in disease therapy; they have been used to image, detect and treat different forms of diseased tissue including age-related macular degeneration and a number of different cancer types. Current focus is on the clinical imaging of tumour tissue; targeted delivery of photosensitisers and the potential of photosensitisers in multimodal biomedical theranostic nanoplatforms. The roles of porphyrinic molecules in imaging and pdt, along with research into improving their selective uptake in diseased tissue and their utility in theranostic applications are highlighted in this Review. PMID:23082103

An unusual pathogen in ambulatory care: two cases of Scedosporium soft tissue infections presenting as "unresponsive cellulitis".

PubMed

Misselbrook, Gary Peter; Lillie, Patrick; Thomas, Claire P

2016-01-01

Soft tissue infections with Scedosporium spp. are an uncommon but serious and emerging cause of infection in immunocompromised patients. Acute Medical Units (AMUs) in the UK are increasingly managing patients with cellulitis in an outpatient setting, therefore acute physicians should be aware of some of the more uncommon causes of soft tissue infection, particularly in patients not responding to initial antibiotic therapy. We present two cases of Scedosporium presenting to the AMU as cellulitis not responding to initial antibiotic therapy and outline the assessment and management of this important condition.

Application of Disposable Bag Bioreactors in Tissue Engineering and for the Production of Therapeutic Agents

NASA Astrophysics Data System (ADS)

Eibl, R.; Eibl, D.

In order to increase process efficiency, many pharmaceutical and biotechnology companies have introduced disposable bag technology over the last 10 years. Because this technology also greatly reduces the risk of cross-contamination, disposable bags are preferred in applications in which an absolute or improved process safety is a necessity, namely the production of functional tissue for implantation (tissue engineering), the production of human cells for the treatment of cancer and immune system diseases (cellular therapy), the production of viruses for gene therapies, the production of therapeutic proteins, and veterinary as well as human vaccines.

Next Generation Mesenchymal Stem Cell (MSC)–Based Cartilage Repair Using Scaffold-Free Tissue Engineered Constructs Generated with Synovial Mesenchymal Stem Cells

PubMed Central

Shimomura, Kazunori; Ando, Wataru; Moriguchi, Yu; Sugita, Norihiko; Yasui, Yukihiko; Koizumi, Kota; Fujie, Hiromichi; Hart, David A.; Yoshikawa, Hideki

2015-01-01

Because of its limited healing capacity, treatments for articular cartilage injuries are still challenging. Since the first report by Brittberg, autologous chondrocyte implantation has been extensively studied. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell–based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. This review summarizes latest development of stem cell therapies in cartilage repair with special attention to scaffold-free approaches. PMID:27340513

Amniotic fluid stem cells: a promising therapeutic resource for cell-based regenerative therapy.

PubMed

Antonucci, Ivana; Pantalone, Andrea; Tete, Stefano; Salini, Vincenzo; Borlongan, Cesar V; Hess, David; Stuppia, Liborio

2012-01-01

Stem cells have been proposed as a powerful tool in the treatment of several human diseases, both for their ability to represent a source of new cells to replace those lost due to tissue injuries or degenerative diseases, and for the ability of produce trophic molecules able to minimize damage and promote recovery in the injured tissue. Different cell types, such as embryonic, fetal or adult stem cells, human fetal tissues and genetically engineered cell lines, have been tested for their ability to replace damaged cells and to restore the tissue function after transplantation. Amniotic fluid -derived Stem cells (AFS) are considered a novel resource for cell transplantation therapy, due to their high renewal capacity, the "in vitro" expression of embryonic cell lineage markers, and the ability to differentiate in tissues derived from all the three embryonic layers. Moreover, AFS do not produce teratomas when transplanted into animals and are characterized by a low antigenicity, which could represent an advantage for cell transplantation or cell replacement therapy. The present review focuses on the biological features of AFS, and on their potential use in the treatment of pathological conditions such as ischemic brain injury and bone damages.

Bone tissue engineering: state of the art and future trends.

PubMed

Salgado, António J; Coutinho, Olga P; Reis, Rui L

2004-08-09

Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds processed by using a methodology based on extrusion with blowing agents.

3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

PubMed Central

Thomas, Michaela; Willerth, Stephanie M.

2017-01-01

Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone), and poly(ethylene glycol). This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work. PMID:29204424

Subsurface thermal coagulation of tissues using near infrared lasers

NASA Astrophysics Data System (ADS)

Chang, Chun-Hung Jack

Noninvasive laser therapy is currently limited primarily to cosmetic dermatological applications such as skin resurfacing, hair removal, tattoo removal and treatment of vascular birthmarks. In order to expand applications of noninvasive laser therapy, deeper optical penetration of laser radiation in tissue as well as more aggressive cooling of the tissue surface is necessary. The near-infrared laser wavelength of 1075 nm was found to be the optimal laser wavelength for creation of deep subsurface thermal lesions in liver tissue, ex vivo, with contact cooling, preserving a surface tissue layer of 2 mm. Monte Carlo light transport, heat transfer, and Arrhenius integral thermal damage simulations were conducted at this wavelength, showing good agreement between experiment and simulations. Building on the initial results, our goal is to develop new noninvasive laser therapies for application in urology, specifically for treatment of female stress urinary incontinence (SUI). Various laser balloon probes including side-firing and diffusing fibers were designed and tested for both transvaginal and transurethral approaches to treatment. The transvaginal approach showed the highest feasibility. To further increase optical penetration depth, various types and concentrations of optical clearing agents were also explored. Three cadavers studies were performed to investigate and demonstrate the feasibility of laser treatment for SUI.

Distribution of phthalocyanines and Raman reporters in human cancerous and noncancerous breast tissue as studied by Raman imaging.

PubMed

Brozek-Pluska, Beata; Jarota, Arkadiusz; Jablonska-Gajewicz, Joanna; Kordek, Radzislaw; Czajkowski, Wojciech; Abramczyk, Halina

2012-08-01

There is a considerable interest in the developing new diagnostic techniques allowing noninvasive tracking of the progress of therapies used to treat a cancer. Raman imaging of distribution of phthalocyanine photosensitizers may open new possibilities of Photodynamic Therapy (PDT) to treat a wide range of neoplastic lesions with improved effectiveness of treatment through precise identification of malignant areas. We have employed Raman imaging and Raman spectroscopy to analyze human breast cancer tissue that interacts with photosensitizers used in the photodynamic therapy of cancer. PCA (Principal Component Analysis) has been employed to analyze various areas of the noncancerous and cancerous breast tissues. The results show that the emission spectra combined with the Raman images are very sensitive indicators to specify the aggregation state and the distribution of phthalocyanines in the cancerous and noncancerous breast tissues. Our results provide experimental evidence on the role of aggregation of phthalocyanines as a factor of particular significance in differentiation of the normal and tumourous (cancerous or benign pathology) breast tissues. We conclude that the Raman imaging reported here has a potential to be a novel and effective photodynamic therapeutic method with improved selectivity for the treatment of breast cancer.

Monitoring high-intensity focused ultrasound (HIFU) therapy using radio frequency ultrasound backscatter to quantify heating

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Anand, Ajay

2005-09-01

The spatial distribution and temporal history of tissue temperature is an essential indicator of thermal therapy progress, and treatment safety and efficacy. Magnetic resonance methods provide the gold standard noninvasive measurement of temperature but are costly and cumbersome compared to the therapy itself. We have been developing the use of ultrasound backscattering for real-time temperature estimation; ultrasonic methods have been limited to relatively low temperature rise, primarily due to lack of sensitivity at protein denaturation temperatures (50-70°C). Through validation experiments on gel phantoms and ex vivo tissue we show that temperature rise can be accurately mapped throughout the therapeutic temperature range using a new BioHeat Transfer Equation (BHTE) model-constrained inverse approach. Speckle-free temperature and thermal dose maps are generated using the ultrasound calibrated model over the imaged region throughout therapy delivery and post-treatment cooling periods. Results of turkey breast tissue experiments are presented for static HIFU exposures, in which the ultrasound calibrated BHTE temperature maps are shown to be very accurate (within a degree) using independent thermocouple measurements. This new temperature monitoring method may speed clinical adoption of ultrasound-guided HIFU therapy. [Work supported by Army MRMC.

The rationale for microcirculatory guided fluid therapy.

PubMed

Ince, Can

2014-06-01

The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac output to improve microcirculatory perfusion and tissue oxygenation. Observation of the microcirculation using handheld microscopes gives insight into the nature of convective and diffusive defect in hypovolemia. The purpose of this article is to introduce a new platform for hemodynamic-targeted fluid therapy based on the correction of tissue and microcirculatory perfusion assumed to be at risk during hypovolemia. Targeting systemic hemodynamic targets and/or clinical surrogates of hypovolemia gives inadequate guarantee for the correction of tissue perfusion by fluid therapy especially in conditions of distributive shock as occur in inflammation and sepsis. Findings are presented, which support the idea that only clinical signs of hypovolemia associated with low microcirculatory flow can be expected to benefit from fluid therapy and that fluid overload causes a defect in the diffusion of oxygen transport. We hypothesized that the optimal amount of fluid needed for correction of hypovolemia is defined by a physiologically based functional microcirculatory hemodynamic platform where convection and diffusion need to be optimized. Future clinical trials using handheld microscopes able to automatically evaluate the microcirculation at the bedside will show whether such a platform will indeed optimize fluid therapy.

The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widder, Joachim, E-mail: j.widder@umcg.nl; Schaaf, Arjen van der; Lambin, Philippe

Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be testedmore » in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.« less

Sequential therapy with "vacuum sealing drainage-artificial dermis implantation-thin partial thickness skin grafting" for deep and infected wound surfaces in children.

PubMed

Yuan, X-G; Zhang, X; Fu, Y-X; Tian, X-F; Liu, Y; Xiao, J; Li, T-W; Qiu, L

2016-05-01

To evaluate the efficacy of a "vacuum sealing drainage (VSD) - artificial dermis implantation (ADI) - thin partial thickness skin grafting (TSG)" sequential therapy for deep and infected wounds in children. Fifty-three pediatric patients with deep and infected wounds were treated with sequential VSD-ADI-TSG therapy. The efficacy of this treatment was compared with that of the surgical debridement-change dressings-thin partial thickness skin grafting previously performed on 20 patients. Survival of tissue grafts, color and flexibility, subcutaneous fullness and scar formation of the graft site were examined and compared. The sequential therapy combined the advantages of the VSD treatment, in reducing tissue necrosis and infection on the wound surfaces and promoting the growth of granulation tissue, with the enhancement of grafting by artificial dermis. Compared with the 20 controls, skin grafted on the artificial dermis was more smooth and glossy, while the textures of the region were more elastic, and the scars were significantly lighter in Vancouver scale. The sequential VSD-ADI-TSG therapy is a simple and effective treatment for children with deep and infected wounds. IV. Copyright © 2016. Published by Elsevier Masson SAS.

De Novo Kidney Regeneration with Stem Cells

PubMed Central

Yokote, Shinya; Yamanaka, Shuichiro; Yokoo, Takashi

2012-01-01

Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration. PMID:23251079

Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery

ClinicalTrials.gov

2018-05-23

FNCLCC Sarcoma Grade 2; FNCLCC Sarcoma Grade 3; Leiomyosarcoma; Liposarcoma; Stage I Soft Tissue Sarcoma AJCC v7; Stage IA Soft Tissue Sarcoma AJCC v7; Stage IB Soft Tissue Sarcoma AJCC v7; Stage II Soft Tissue Sarcoma AJCC v7; Stage IIA Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Undifferentiated Pleomorphic Sarcoma

Review of 3D image data calibration for heterogeneity correction in proton therapy treatment planning.

PubMed

Zhu, Jiahua; Penfold, Scott N

2016-06-01

Correct modelling of the interaction parameters of patient tissues is of vital importance in proton therapy treatment planning because of the large dose gradients associated with the Bragg peak. Different 3D imaging techniques yield different information regarding these interaction parameters. Given the rapidly expanding interest in proton therapy, this review is written to make readers aware of the current challenges in accounting for tissue heterogeneities and the imaging systems that are proposed to tackle these challenges. A summary of the interaction parameters of interest in proton therapy and the current and developmental 3D imaging techniques used in proton therapy treatment planning is given. The different methods to translate the imaging data to the interaction parameters of interest are reviewed and a summary of the implementations in several commercial treatment planning systems is presented.

Prostate tissue ablation with MRI guided transurethral therapeutic ultrasound and intraoperative assessment of the integrity of the neurovascular bundle

NASA Astrophysics Data System (ADS)

Sammet, Steffen; Partanen, Ari; Yousuf, Ambereen; Wardrip, Craig; Niekrasz, Marek; Antic, Tatjana; Razmaria, Aria; Sokka, Sham; Karczmar, Gregory; Oto, Aytekin

2017-03-01

OBJECTIVES: Evaluation of the precision of prostate tissue ablation with MRI guided therapeuticultrasound by intraoperative objective assessment of the neurovascular bundle in canines in-vivo. METHODS: In this ongoing IACUC approved study, eight male canines were scanned in a clinical 3T Achieva MRI scanner (Philips) before, during, and after ultrasound therapy with a prototype MR-guided ultrasound therapy system (Philips). The system includes a therapy console to plan treatment, to calculate real-time temperature maps, and to control ultrasound exposures with temperature feedback. Atransurethral ultrasound applicator with eight transducer elements was used to ablate canine prostate tissue in-vivo. Ablated prostate tissue volumes were compared to the prescribed target volumes to evaluate technical effectiveness. The ablated volumes determined by MRI (T1, T2, diffusion, dynamic contrast enhanced and 240 CEM43 thermal dose maps) were compared to H&E stained histological slides afterprostatectomy. Potential nerve damage of the neurovascular bundle was objectively assessed intraoperativelyduring prostatectomy with a CaverMap Surgical Aid nerve stimulator (Blue Torch Medical Technologies). RESULTS: Transurethral MRI -guided ultrasound therapy can effectively ablate canine prostate tissue invivo. Coronal MR-imaging confirmed the correct placement of the HIFU transducer. MRI temperature maps were acquired during HIFU treatment, and subsequently used for calculating thermal dose. Prescribed target volumes corresponded to the 240 CEM43 thermal dose maps during HIFU treatment in all canines. Ablated volumes on high resolution anatomical, diffusion weighted, and contrast enhanced MR images matched corresponding histological slides after prostatectomy. MRI guidance with realtime temperature monitoring showed no damage to surrounding tissues, especially to the neurovascular bundle (assessed intra-operatively with a nerve stimulator) or to the rectum wall. CONCLUSIONS: Our study demonstrates the effectiveness and precision of transurethral ultrasound ablation of prostatic tissue in canines with MRI monitoring and guidance. The canine prostate is an excellent model for the human prostate with similar anatomical characteristics and diseases. MRI guidance with real-time, intraoperative temperature monitoring reduces the risk of damaging critical surrounding anatomical structures in ultrasound therapy of the prostate.

Two-photon induced collagen cross-linking in bioartificial cardiac tissue

NASA Astrophysics Data System (ADS)

Kuetemeyer, Kai; Kensah, George; Heidrich, Marko; Meyer, Heiko; Martin, Ulrich; Gruh, Ina; Heisterkamp, Alexander

2011-08-01

Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs for transplantation. Besides contractile function, the stiffness of tissue engineered constructs is crucial to generate transplantable tissue surrogates with sufficient mechanical stability to withstand the high pressure present in the heart. Although several collagen cross-linking techniques have proven to be efficient in stabilizing biomaterials, they cannot be applied to cardiac tissue engineering, as cell death occurs in the treated area. Here, we present a novel method using femtosecond (fs) laser pulses to increase the stiffness of collagen-based tissue constructs without impairing cell viability. Raster scanning of the fs laser beam over riboflavin-treated tissue induced collagen cross-linking by two-photon photosensitized singlet oxygen production. One day post-irradiation, stress-strain measurements revealed increased tissue stiffness by around 40% being dependent on the fibroblast content in the tissue. At the same time, cells remained viable and fully functional as demonstrated by fluorescence imaging of cardiomyocyte mitochondrial activity and preservation of active contraction force. Our results indicate that two-photon induced collagen cross-linking has great potential for studying and improving artificially engineered tissue for regenerative therapies.

Mesenchymal stem cell therapy for attenuation of scar formation during wound healing.

PubMed

Jackson, Wesley M; Nesti, Leon J; Tuan, Rocky S

2012-05-31

Scars are a consequence of cutaneous wound healing that can be both unsightly and detrimental to the function of the tissue. Scar tissue is generated by excessive deposition of extracellular matrix tissue by wound healing fibroblasts and myofibroblasts, and although it is inferior to the uninjured skin, it is able to restore integrity to the boundary between the body and its environment. Scarring is not a necessary process to repair the dermal tissues. Rather, scar tissue forms due to specific mechanisms that occur during the adult wound healing process and are modulated primarily by the inflammatory response at the site of injury. Adult tissue-derived mesenchymal stem cells, which participate in normal wound healing, are trophic mediators of tissue repair. These cells participate in attenuating inflammation in the wound and reprogramming the resident immune and wound healing cells to favor tissue regeneration and inhibit fibrotic tissue formation. As a result, these cells have been considered and tested as a likely candidate for a cellular therapy to promote scar-less wound healing. This review identifies specific mechanisms by which mesenchymal stem cells can limit tissue fibrosis and summarizes recent in vivo studies where these cells have been used successfully to limit scar formation.

Laser interaction with tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berns, M.W.

These proceedings collect papers on laser biomedicine. Topics include: light distributions on tissue; chemical byproducts of laser/tissue interactions; laser applications in ophthalmology; phododynamic therapy; diode pumped solid state lasers at two and three micrometers; and applications of excimer lasers to peripheral nerve repair.

Dosimetry control and monitoring of selective retina therapy using optical coherence tomography

NASA Astrophysics Data System (ADS)

Kaufmann, Daniel; Burri, Christian; Arnold, Patrik; Koch, Volker M.; Meier, Christoph; Považay, Boris; Justiz, Joern

2017-07-01

Selective retina therapy and optical coherence tomography have been combined to monitor laser-tissue interaction in real-time. An ex-vivo study of porcine eyes unveils mechanisms that enable automated and accurate dose-control during laser-therapy.

Tissue engineering applications of therapeutic cloning.

PubMed

Atala, Anthony; Koh, Chester J

2004-01-01

Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for replacement therapy. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

Pericyte-targeting drug delivery and tissue engineering.

PubMed

Kang, Eunah; Shin, Jong Wook

2016-01-01

Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes.

Advances in prevention of radiation damage to visceral and solid organs in patients requiring radiation therapy of the trunk.

PubMed

Ritter, E F; Lee, C G; Tyler, D; Ferraro, F; Whiddon, C; Rudner, A M; Scully, S

1997-02-01

As a part of multimodality therapy, many patients with tumors of the trunk receive radiation therapy. The major morbidity of this therapy is often secondary to incidental radiation damage to tissues adjacent to treatment areas. We detail our use of saline breast implants placed in polyglycolic acid mesh sheets to displace visceral and solid organs away from the radiation field. Analysis of CT scans and dose volume histograms reveal that this technique successfully displaces uninvolved organs away from the radiation fields, thereby minimizing the radiation dose to such organs and tissues. We believe this is a safe and efficacious method to prevent radiation damage to visceral and solid organs adjacent to trunk tumor sites.

Platelet-Rich Plasma Peptides: Key for Regeneration

PubMed Central

Sánchez-González, Dolores Javier; Méndez-Bolaina, Enrique; Trejo-Bahena, Nayeli Isabel

2012-01-01

Platelet-derived Growth Factors (GFs) are biologically active peptides that enhance tissue repair mechanisms such as angiogenesis, extracellular matrix remodeling, and cellular effects as stem cells recruitment, chemotaxis, cell proliferation, and differentiation. Platelet-rich plasma (PRP) is used in a variety of clinical applications, based on the premise that higher GF content should promote better healing. Platelet derivatives represent a promising therapeutic modality, offering opportunities for treatment of wounds, ulcers, soft-tissue injuries, and various other applications in cell therapy. PRP can be combined with cell-based therapies such as adipose-derived stem cells, regenerative cell therapy, and transfer factors therapy. This paper describes the biological background of the platelet-derived substances and their potential use in regenerative medicine. PMID:22518192

[Focused ultrasound therapy: current status and potential applications in neurosurgery].

PubMed

Dervishi, E; Aubry, J-F; Delattre, J-Y; Boch, A-L

2013-12-01

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

INFLUENCE OF OZONE THERAPY ON ORAL TISSUE IN MODELING OF CHRONIC RECURRENT APHTHOUS STOMATITIS.

PubMed

Kovach, I; Kravchenko, L; Khotimska, Yu; Nazaryan, R; Gargin, V

2017-03-01

Chronic recurrent aphthous stomatitis (CRAS) belongs to the group of chronic, inflammatory, ulcerative diseases of the oral mucosa. The aim of this study was to determine the effects of ozone on the morphofunctional peculiarities of the soft tissues in modeling chronic recurrent aphthous stomatitis. We performed experimental investigation for study of the morpho-functional state of tissues of the oral mucosa in CRAS with using of previously proposed and widely used modeling scheme with ovalbumin and aluminum hydroxide. Two groups of animals were formed (Dutch rabbits, males, aging three-month, weighting 2-2.4 kg). Group of 8 animals with obtained mucosal changes was our comparison group. Other group of 8 animals with obtained mucosal changes was treated by ozone therapy. Histological investigation has been performed. Microscopical examination of tissue had shown that ozone therapy reduces inflammation and edema and is useful in wound healing in soft tissue as disappearance of necrobiotic processes, epithelialization of aphthous defect, growth of akantotic bands, pronounced reducing of inflammatory cells and changing of cellular ratio (with of neutrophils part from 38.30±2.46% to 6.34±0.63%, eosinophils from 5.49±0.23% to 2.87±0.05%), restoration of the cellular layers of the epithelium, moderately pronounced sclerosis of the papillary layer of the lamina propria. Described results allow to conclude that correction of tissual changes in chronic recurrent aphthous stomatitis could be obtained with ozone therapy using.

Both serum and tissue Galectin-1 levels are associated with adverse clinical features in neuroblastoma.

PubMed

Chen, Kai; Cai, Yuanxia; Zhang, Min; Wu, Zhixiang; Wu, Yeming

2018-05-24

Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy. © 2018 Wiley Periodicals, Inc.

Optoacoustic theranostics

NASA Astrophysics Data System (ADS)

Petrov, Irene Y.; Micci, Maria-Adelaide; Prough, Donald S.; Petrov, Yuriy; Guptarak, Jutatip; Grant, Auston C.; Parsley, Margaret A.; Bolding, Ian J.; Esenaliev, Rinat O.

2018-03-01

Optoacoustic diagnostics is based on detection and analysis of optoacoustic waves induced in tissues. It may find a number of important clinical applications in large populations of patients such as diagnostics of cerebral hypoxia, circulatory shock, etc. Recently, we proposed Nano-Pulse Laser Therapy (NPLT) which utilizes short optical pulses (typically, shorter than hundreds of nanoseconds) to generate optoacoustic waves in tissues upon stress-confined irradiation. It is well known that continuous wave low-level near-infrared light can be used for therapy/photobiomodulation to stimulate, repair, regenerate, and protect injured tissue. In the past few years, new works emerged on therapeutic effects of low-intensity ultrasound waves. The NPLT consists of irradiating tissue by both lowlevel light and optoacoustic waves/ultrasound that combines merits of low-level light and ultrasound therapies. In this work we propose optoacoustic theranostics that can be used for diagnostics, optoacoustic therapy/NPLT, and monitoring of therapeutic response during and after therapy. We developed and built pulsed, tunable, near infrared (680-1064 nm), fiber-coupled systems for optoacoustic theranostics and tested them in rats with traumatic brain injury (TBI). Low energy pulses were used for optoacoustic monitoring of cerebral blood oxygenation, while higher energy pulses were used for the NPLT. Our studies show that TBI results in cerebral hypoxia, while a 5-minute transcranial application of NPLT significantly reduces negative effects of TBI as assessed by vestibulomotor, cognitive, and immunofluorescence tests. The obtained results suggest that the optoacoustic theranostics may be used for diagnostics and management of TBI and other disorders.

Upper bound dose values for meson radiation in heavy-ion therapy.

PubMed

Rabin, C; Gonçalves, M; Duarte, S B; González-Sprinberg, G A

2018-06-01

Radiation treatment of cancer has evolved to include massive particle beams, instead of traditional irradiation procedures. Thus, patient doses and worker radiological protection have become issues of constant concern in the use of these new technologies, especially for proton- and heavy-ion-therapy. In the beam energies of interest of heavy-ion-therapy, secondary particle radiation comes from proton, neutron, and neutral and charged pions produced in the nuclear collisions of the beam with human tissue atoms. This work, for the first time, offers the upper bound of meson radiation dose in organic tissues due to secondary meson radiation in heavy-ion therapy. A model based on intranuclear collision has been used to follow in time the nuclear reaction and to determine the secondary radiation due to the meson yield produced in the beam interaction with nuclei in the tissue-equivalent media and water. The multiplicity, energy spectrum, and angular distribution of these pions, as well as their decay products, have been calculated in different scenarios for the nuclear reaction mechanism. The results of the produced secondary meson particles has been used to estimate the energy deposited in tissue using a cylindrical phantom by a transport Monte Carlo simulation and we have concluded that these mesons contribute at most 0.1% of the total prescribed dose.

Evaluation of a mixed beam therapy for post-mastectomy breast cancer patients: bolus electron conformal therapy combined with intensity modulated photon radiotherapy and volumetric modulated photon arc therapy.

PubMed

Zhang, Rui; Heins, David; Sanders, Mary; Guo, Beibei; Hogstrom, Kenneth

2018-05-10

The purpose of this study was to assess the potential benefits and limitations of a mixed beam therapy, which combined bolus electron conformal therapy (BECT) with intensity modulated photon radiotherapy (IMRT) and volumetric modulated photon arc therapy (VMAT), for left-sided post-mastectomy breast cancer patients. Mixed beam treatment plans were produced for nine post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic with VMAT alone. The mixed beam plans consisted of 40 Gy to the chest wall area using BECT, 40 Gy to the supraclavicular area using parallel opposed IMRT, and 10 Gy to the total planning target volume (PTV) by optimizing VMAT on top of the BECT+IMRT dose distribution. The treatment plans were created in a commercial treatment planning system (TPS), and all plans were evaluated based on PTV coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The standard VMAT alone planning technique was used as the reference for comparison. Both techniques produced clinically acceptable PMRT plans but with a few significant differences: VMAT showed significantly better CI (0.70 vs. 0.53, p < 0.001) and DHI (0.12 vs. 0.20, p < 0.001) over mixed beam therapy. For normal tissues, mixed beam therapy showed better OAR sparing and significantly reduced NTCP for cardiac mortality (0.23% vs. 0.80%, p = 0.01) and SCCP for contralateral breast (1.7% vs. 3.1% based on linear model, and 1.2% vs. 1.9% based on linear-exponential model, p < 0.001 in both cases), but showed significantly higher mean (50.8 Gy vs. 49.3 Gy, p < 0.001) and maximum skin doses (59.7 Gy vs. 53.3 Gy, p < 0.001) compared with VMAT. Patients with more tissue (minimum distance between the distal PTV surface and lung approximately > 0.5 cm and volume of tissue between the distal PTV surface and heart or lung approximately > 250 cm 3 ) between distal PTV surface and lung may benefit the most from mixed beam therapy. This work has demonstrated that mixed beam therapy (BECT+IMRT : VMAT = 4 : 1) produces clinically acceptable plans having reduced OAR doses and risks of side effects compared with VMAT. Even though VMAT alone produces more homogenous and conformal dose distributions, mixed beam therapy remains as a viable option for treating post-mastectomy patients, possibly leading to reduced normal tissue complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

77 FR 61004 - Request for Nominations for Voting Members on Public Advisory Committees

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

...--individuals knowledgeable in tissue engineering/regenerative medicine, orthopedic oncology. [[Page 61005... Committee, Cellular, Tissue and Gene Therapies Advisory Committee, and Transmissible Spongiform and... . Advisory Committee. Gail Dapolito, Center for Biologics Cellular, Tissue and Gene Evaluation and Research...

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gay, Hiram A., E-mail: hgay@radonc.wustl.edu; Barthold, H. Joseph; Beth Israel Deaconess Medical Center, Boston, MA

2012-07-01

Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The followingmore » were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.« less

Cupping therapy: An analysis of the effects of suction on skin and the possible influence on human health.

PubMed

Lowe, Duane T

2017-11-01

Cupping therapy is a traditional therapy that has been employed worldwide for thousands of years. Despite a lack of quality clinical studies evaluating the efficacy of cupping therapy, its long history and widespread use throughout the world suggests the commonly claimed health benefits should not be completely discounted as without merit. The goal of this paper is to present the research detailing what is known concerning the effects of suction on skin and underlying tissue, and the reaction of the body to that stimulus. Understanding the literature on the physiological effects of this mechanical force may help elaborate an explanation for the advertised local and systemic effects of cupping therapy. Negative pressure causes stretching of the skin and underlying tissue and dilation of the capillaries. This stimulates an increase in tissue blood flow, eventually leading to capillary rupture and ecchymosis. Macrophages phagocytize the erythrocytes in the extravascular space which stimulates the production of Heme Oxygenase-1 (HO-1) to metabolize the heme. Heme catalysis results in the production of carbon monoxide (CO), biliverdin(BV)/bilirubin(BR) and iron. HO-1, BV, BR, and CO has been shown to have antioxidant, anti-inflammatory, antiproliferative, and neuromodulatory effects in animal and human systems. These substances also stimulate a shift of macrophages to the anti-inflammatory M2 phenotype. There is evidence that the effects are both local and systemic. Besides the mechanical effect of cupping increasing the local blood flow and stretching underlying tissue, activation of the HO-1 system could account for many of cupping therapy's claimed local and systemic health benefits. Published by Elsevier Ltd.

Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?

PubMed Central

Patel, S.A.; King, C.C.; Lim, P.K.; Habiba, U.; Dave, M.; Porecha, R.; Rameshwar, P.

2010-01-01

The euphoria of stem cell therapy has diminished, allowing scientists, clinicians and the general public to seriously re-examine how and what types of stem cells would effectively repair damaged tissue, prevent further tissue damage and/or replace lost cells. Importantly, there is a growing recognition that there are substantial person-to-person differences in the outcome of stem cell therapy. Even though the small molecule pharmaceuticals have long remained a primary focus of the personalized medicine research, individualized or targeted use of stem cells to suit a particular individual could help forecast potential failures of the therapy or identify, early on, the individuals who might benefit from stem cell interventions. This would however demand collaboration among several specialties such as pharmacology, immunology, genomics and transplantation medicine. Such transdisciplinary work could also inform how best to achieve efficient and predictable stem cell migration to sites of tissue damage, thereby facilitating tissue repair. This paper discusses the possibility of polarizing immune responses to rationalize and individualize therapy with stem cell interventions, since generalized “one-size-fits-all” therapy is difficult to achieve in the face of the diverse complexities posed by stem cell biology. We also present the challenges to stem cell delivery in the context of the host related factors. Although we focus on the mesenchymal stem cells in this paper, the overarching rationale can be extrapolated to other types of stem cells as well. Hence, the broader purpose of this paper is to initiate a dialogue within the personalized medicine community by expanding the scope of inquiry in the field from pharmaceuticals to stem cells and related cell-based health interventions. PMID:20563265

Accessibility of ³H-secoisolariciresinol diglycoside lignan metabolites in skeletal tissue of ovariectomized rats.

PubMed

Sacco, Sandra M; Thompson, Lilian U; Ganss, Bernhard; Ward, Wendy E

2011-10-01

Flaxseed, rich in the phytoestrogen lignan secoisolariciresinol diglycoside (SDG), provides protection against bone loss at the lumbar vertebrae primarily when combined with low-dose estrogen therapy in the ovariectomized rat model of postmenopausal osteoporosis. Whether SDG metabolites are accessible to skeletal tissue, and thus have the potential to interact with low-dose estrogen therapy to exert direct local action on bone metabolism, is unknown. The objective of this study was to determine whether metabolites of SDG are accessible to the skeleton of ovariectomized rats and to compare the distribution of SDG metabolites in skeletal tissue with that in other tissues. Rats were fed a 10% flaxseed diet and gavaged daily with tritium-labeled SDG (7.4 kBq/g of body weight) in deionized water (500 μL) (n=3) or deionized water alone (n=3) for 7 days, after which tissues were collected for liquid scintillation counting. Radioactivity was detected in similar concentrations in the lumbar vertebrae, femurs, and tibias. Compared with non-skeletal tissues, total radioactivity in the skeleton was significantly lower than in the liver, heart, kidney, thymus, and brain (P < .001). There were no significant differences in levels of radioactivity between skeletal tissue versus the spleen, lung, bladder, uterus, vagina, and mammary gland. In conclusion, SDG metabolites are accessible to skeletal tissue of ovariectomized rats. Thus, it is biologically plausible that SDG metabolites may play a direct role in the protective effects of flaxseed combined with low-dose estrogen therapy against the loss of bone mass and bone strength in the ovariectomized rat model of postmenopausal osteoporosis.

Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

PubMed

Park, Susanna S

2016-04-01

Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review)

PubMed Central

WAN, CAIFENG; LI, FENGHUA; LI, HONGLI

2015-01-01

The eye is an ideal target organ for gene therapy as it is easily accessible and immune-privileged. With the increasing insight into the underlying molecular mechanisms of ocular diseases, gene therapy has been proposed as an effective approach. Successful gene therapy depends on efficient gene transfer to targeted cells to prove stable and prolonged gene expression with minimal toxicity. At present, the main hindrance regarding the clinical application of gene therapy is not the lack of an ideal gene, but rather the lack of a safe and efficient method to selectively deliver genes to target cells and tissues. Ultrasound-targeted microbubble destruction (UTMD), with the advantages of high safety, repetitive applicability and tissue targeting, has become a potential strategy for gene- and drug delivery. When gene-loaded microbubbles are injected, UTMD is able to enhance the transport of the gene to the targeted cells. High-amplitude oscillations of microbubbles act as cavitation nuclei which can effectively focus ultrasound energy, produce oscillations and disruptions that increase the permeability of the cell membrane and create transient pores in the cell membrane. Thereby, the efficiency of gene therapy can be significantly improved. The UTMD-mediated gene delivery system has been widely used in pre-clinical studies to enhance gene expression in a site-specific manner in a variety of organs. With reasonable application, the effects of sonoporation can be spatially and temporally controlled to improve localized tissue deposition of gene complexes for ocular gene therapy applications. In addition, appropriately powered, focused ultrasound combined with microbubbles can induce a reversible disruption of the blood-retinal barrier with no significant side effects. The present review discusses the current status of gene therapy of ocular diseases as well as studies on gene therapy of ocular diseases meditated by UTMD. PMID:26151686

Chronic ankle pain and fibrosis successfully treated with a new noninvasive augmented soft tissue mobilization technique (ASTM): a case report.

PubMed

Melham, T J; Sevier, T L; Malnofski, M J; Wilson, J K; Helfst, R H

1998-06-01

This clinical case report demonstrates the clinical effectiveness of a new form of soft tissue mobilization in the treatment of excessive connective tissue fibrosis (scar tissue) around an athlete's injured ankle. The scar tissue was causing the athlete to have pain with activity, pain on palpation of the ankle, decreased range of motion, and loss of function. Surgery and several months of conventional physical therapy failed to alleviate the athlete's symptoms. As a final resort, augmented soft tissue mobilization (ASTM) was administered. ASTM is an alternative nonsurgical treatment modality that is being researched at Performance Dynamics (Muncip, IN). ASTM is a process that uses ergonomically designed instruments that assist therapists in the rapid localization and effective treatment of areas exhibiting excessive soft tissue fibrosis. This is followed by a stretching and strengthening program. Upon the completion of 6 wk of ASTM therapy, the athlete had no pain and had regained full range of motion and function. This case report is an example of how a noninvasive augmented form of soft tissue mobilization (ASTM) demonstrated impressive clinical results in treating a condition caused by connective tissue fibrosis.

Stem cell homing-based tissue engineering using bioactive materials

NASA Astrophysics Data System (ADS)

Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

2017-06-01

Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

Tissue engineering: current strategies and future directions.

PubMed

Olson, Jennifer L; Atala, Anthony; Yoo, James J

2011-04-01

Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future.

Tissue engineering and cell-based therapy toward integrated strategy with artificial organs.

PubMed

Gojo, Satoshi; Toyoda, Masashi; Umezawa, Akihiro

2011-09-01

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.

Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies.

PubMed

Kirkton, Robert D; Bursac, Nenad

2011-01-01

Patch-clamp recordings in single-cell expression systems have been traditionally used to study the function of ion channels. However, this experimental setting does not enable assessment of tissue-level function such as action potential (AP) conduction. Here we introduce a biosynthetic system that permits studies of both channel activity in single cells and electrical conduction in multicellular networks. We convert unexcitable somatic cells into an autonomous source of electrically excitable and conducting cells by stably expressing only three membrane channels. The specific roles that these expressed channels have on AP shape and conduction are revealed by different pharmacological and pacing protocols. Furthermore, we demonstrate that biosynthetic excitable cells and tissues can repair large conduction defects within primary 2- and 3-dimensional cardiac cell cultures. This approach enables novel studies of ion channel function in a reproducible tissue-level setting and may stimulate the development of new cell-based therapies for excitable tissue repair.

Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip.

PubMed

Doryab, Ali; Amoabediny, Ghassem; Salehi-Najafabadi, Amir

2016-01-01

Lung disease is one of the major causes of death, and the rate of pulmonary diseases has been increasing for decades. Although lung transplantation is the only treatment for majority of patients, this method has been limited due to lack of donors. Therefore, recently, attentions have increased to some new strategies with the aid of tissue engineering and microfluidics techniques not only for the functional analysis, but also for drug screening. In fact, in tissue engineering, the engineered tissue is able to grow by using the patient's own cells without intervention in the immune system. On the other hand, microfluidics devices are applied in order to evaluate drug screenings, function analysis and toxicity. This article reviews new advances in lung tissue engineering and lung-on-a-chip. Furthermore, future directions, difficulties and drawbacks of pulmonary therapy in these areas are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Topical oxygen therapy & micro/nanobubbles: a new modality for tissue oxygen delivery.

PubMed

Sayadi, Lohrasb R; Banyard, Derek A; Ziegler, Mary E; Obagi, Zaidal; Prussak, Jordyne; Klopfer, Michael J; Evans, Gregory Rd; Widgerow, Alan D

2018-06-01

Up to 15 billion dollars of US health care expenditure each year is consumed by treatment of poorly healing wounds whose etiologies are often associated with aberrancies in tissue oxygenation. To address this issue, several modes of tissue oxygen delivery systems exist, including Hyperbaric Oxygen Therapy (HBOT) and Topical Oxygen Therapy (TOT), but their efficacies have yet to be fully substantiated. Micro/nanobubbles (MNBs), which range anywhere from 100 μm to <1 μm in diameter and are relatively stable for hours, offer a new mode of oxygen delivery to wounds. The aim of this article is to systematically review literature examining the use of TOT for wound healing and use of MNBs for tissue oxygenation using the MEDLINE database. The search yielded 87 articles (12 MNB articles and 75 TOT articles), of which 52 met the inclusion criteria for this literature review (12 MNB articles and 40 TOT articles). Additionally, we present an analysis on the efficacy of our MNB generating technology and propose its use as a wound healing agent. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Multifunctional cell-culture platform for aligned cell sheet monitoring, transfer printing, and therapy.

PubMed

Kim, Seok Joo; Cho, Hye Rim; Cho, Kyoung Won; Qiao, Shutao; Rhim, Jung Soo; Soh, Min; Kim, Taeho; Choi, Moon Kee; Choi, Changsoon; Park, Inhyuk; Hwang, Nathaniel S; Hyeon, Taeghwan; Choi, Seung Hong; Lu, Nanshu; Kim, Dae-Hyeong

2015-03-24

While several functional platforms for cell culturing have been proposed for cell sheet engineering, a soft integrated system enabling in vitro physiological monitoring of aligned cells prior to their in vivo applications in tissue regeneration has not been reported. Here, we present a multifunctional, soft cell-culture platform equipped with ultrathin stretchable nanomembrane sensors and graphene-nanoribbon cell aligners, whose system modulus is matched with target tissues. This multifunctional platform is capable of aligning plated cells and in situ monitoring of cellular physiological characteristics during proliferation and differentiation. In addition, it is successfully applied as an in vitro muscle-on-a-chip testing platform. Finally, a simple but high-yield transfer printing mechanism is proposed to deliver cell sheets for scaffold-free, localized cell therapy in vivo. The muscle-mimicking stiffness of the platform allows the high-yield transfer printing of multiple cell sheets and results in successful therapies in diseased animal models. Expansion of current results to stem cells will provide unique opportunities for emerging classes of tissue engineering and cell therapy technologies.

Feasibility of the Utilization of BNCT in the Fast Neutron Therapy Beam at Fermilab

DOE R&D Accomplishments Database

Langen, Katja; Lennox, Arlene J.; Kroc, Thomas K.; DeLuca, Jr., Paul M.

2000-06-01

The Neutron Therapy Facility at Fermilab has treated cancer patients since 1976. Since then more than 2,300 patients have been treated and a wealth of clinical information accumulated. The therapeutic neutron beam at Fermilab is produced by bombarding a beryllium target with 66 MeV protons. The resulting continuous neutron spectrum ranges from thermal to 66 MeV in neutron energy. It is clear that this spectrum is not well suited for the treatment of tumors with boron neutron capture therapy (BNCT) only However, since this spectrum contains thermal and epithermal components the authors are investigating whether BNCT can be used in this beam to boost the tumor dose. There are clinical scenarios in which a selective tumor dose boost of 10 - 15% could be clinically significant. For these cases the principal treatment would still be fast neutron therapy but a tumor boost could be used either to deliver a higher dose to the tumor tissue or to reduce the dose to the normal healthy tissue while maintaining the absorbed dose level in the tumor tissue.

Strategies for optimizing the response of cancer and normal tissues to radiation

PubMed Central

Moding, Everett J.; Kastan, Michael B.; Kirsch, David G.

2014-01-01

Approximately 50% of all patients with cancer receive radiation therapy at some point during the course of their treatment, and the majority of these patients are treated with curative intent. Despite recent advances in the planning of radiation treatment and the delivery of image-guided radiation therapy, acute toxicity and potential long-term side effects often limit the ability to deliver a sufficient dose of radiation to control tumours locally. In the past two decades, a better understanding of the hallmarks of cancer and the discovery of specific signalling pathways by which cells respond to radiation have provided new opportunities to design molecularly targeted therapies to increase the therapeutic window of radiation therapy. Here, we review efforts to develop approaches that could improve outcomes with radiation therapy by increasing the probability of tumour cure or by decreasing normal tissue toxicity. PMID:23812271

Simulation of nanoparticle-mediated near-infrared thermal therapy using GATE

PubMed Central

Cuplov, Vesna; Pain, Frédéric; Jan, Sébastien

2017-01-01

Application of nanotechnology for biomedicine in cancer therapy allows for direct delivery of anticancer agents to tumors. An example of such therapies is the nanoparticle-mediated near-infrared hyperthermia treatment. In order to investigate the influence of nanoparticle properties on the spatial distribution of heat in the tumor and healthy tissues, accurate simulations are required. The Geant4 Application for Emission Tomography (GATE) open-source simulation platform, based on the Geant4 toolkit, is widely used by the research community involved in molecular imaging, radiotherapy and optical imaging. We present an extension of GATE that can model nanoparticle-mediated hyperthermal therapy as well as simple heat diffusion in biological tissues. This new feature of GATE combined with optical imaging allows for the simulation of a theranostic scenario in which the patient is injected with theranostic nanosystems that can simultaneously deliver therapeutic (i.e. hyperthermia therapy) and imaging agents (i.e. fluorescence imaging). PMID:28663855

Strategies to Maximize the Potential of Marine Biomaterials as a Platform for Cell Therapy

PubMed Central

Kim, Hyeongmin; Lee, Jaehwi

2016-01-01

Marine biopolymers have been explored as a promising cell therapy system for efficient cell delivery and tissue engineering. However, the marine biomaterial-based systems themselves have exhibited limited performance in terms of maintenance of cell viability and functions, promotion of cell proliferation and differentiation as well as cell delivery efficiency. Thus, numerous novel strategies have been devised to improve cell therapy outcomes. The strategies include optimization of physical and biochemical properties, provision of stimuli-responsive functions, and design of platforms for efficient cell delivery and tissue engineering. These approaches have demonstrated substantial improvement of therapeutic outcomes in a variety of research settings. In this review, therefore, research progress made with marine biomaterials as a platform for cell therapy is reported along with current research directions to further advance cell therapies as a tool to cure incurable diseases. PMID:26821034

Identification of reduced-order thermal therapy models using thermal MR images: theory and validation.

PubMed

Niu, Ran; Skliar, Mikhail

2012-07-01

In this paper, we develop and validate a method to identify computationally efficient site- and patient-specific models of ultrasound thermal therapies from MR thermal images. The models of the specific absorption rate of the transduced energy and the temperature response of the therapy target are identified in the reduced basis of proper orthogonal decomposition of thermal images, acquired in response to a mild thermal test excitation. The method permits dynamic reidentification of the treatment models during the therapy by recursively utilizing newly acquired images. Such adaptation is particularly important during high-temperature therapies, which are known to substantially and rapidly change tissue properties and blood perfusion. The developed theory was validated for the case of focused ultrasound heating of a tissue phantom. The experimental and computational results indicate that the developed approach produces accurate low-dimensional treatment models despite temporal and spatial noises in MR images and slow image acquisition rate.

Cell and Tissue Engineering for Liver Disease

PubMed Central

Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

2015-01-01

Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

Regenerative dentistry: translating advancements in basic science research to the dental practice.

PubMed

Garcia-Godoy, Franklin; Murray, Peter

2010-01-01

Scientific advances in the creation of restorative biomaterials, in vitro cell culture technology, tissue engineering, molecular biology and the human genome project provide the basis for the introduction of new technologies into dentistry. This review provides an assessment of how tissue engineering, stem cell, genetic transfer, biomaterial and growth factor therapies can be integrated into clinical dental therapies to restore and regenerate oral tissues. In parallel to the creation of a new field in general medicine called "regenerative medicine," we call this field "regenerative dentistry." While the problems of introducing regenerative therapies are substantial, the potential benefits to patients and the profession are equally ground-breaking. In this review, we outline a few areas of interest for the future of oral and dental medicine in which advancements in basic science have already been adapted to fit the goals of 21st century dentistry.

Tissue-mimicking gel phantoms for thermal therapy studies.

PubMed

Dabbagh, Ali; Abdullah, Basri Johan Jeet; Ramasindarum, Chanthiriga; Abu Kasim, Noor Hayaty

2014-10-01

Tissue-mimicking phantoms that are currently available for routine biomedical applications may not be suitable for high-temperature experiments or calibration of thermal modalities. Therefore, design and fabrication of customized thermal phantoms with tailored properties are necessary for thermal therapy studies. A multitude of thermal phantoms have been developed in liquid, solid, and gel forms to simulate biological tissues in thermal therapy experiments. This article is an attempt to outline the various materials and techniques used to prepare thermal phantoms in the gel state. The relevant thermal, electrical, acoustic, and optical properties of these phantoms are presented in detail and the benefits and shortcomings of each type are discussed. This review could assist the researchers in the selection of appropriate phantom recipes for their in vitro study of thermal modalities and highlight the limitations of current phantom recipes that remain to be addressed in further studies. © The Author(s) 2014.

Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy

PubMed Central

Kasala, Dayananda; Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

2016-01-01

Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research. PMID:27348247

The potential of nanofibers in tissue engineering and stem cell therapy.

PubMed

Gholizadeh-Ghaleh Aziz, Shiva; Gholizadeh-Ghaleh Aziz, Sara; Akbarzadeh, Abolfazl

2016-08-01

Electrospinning is a technique in which materials in solution are shaped into continuous nano- and micro-sized fibers. Combining stem cells with biomaterial scaffolds and nanofibers affords a favorable approach for bone tissue engineering, stem cell growth and transfer, ocular surface reconstruction, and treatment of congenital corneal diseases. This review seeks to describe the current examples of the use of scaffolds in stem cell therapy. Stem cells are classified as adult or embryonic stem (ES) cells, and the advantages and drawbacks of each group are detailed. The nanofibers and scaffolds are further classified in Tables I and II , which describe specific examples from the literature. Finally, the current applications of biomaterial scaffolds containing stem cells for tissue engineering applications are presented. Overall, this review seeks to give an overview of the biomaterials available for use in combination with stem cells, and the application of nanofibers in stem cell therapy.

Intralesional copper wire retention and pingyangmycin injection: an effective combinational therapy for complex venous malformation in soft tissue.

PubMed

Yuan, S-M; Hong, Z-J; Jiang, H-Q; Wang, J; Hu, X-B

2014-04-01

Complex venous malformations (VMs) may extensively involve the soft tissue. The treatment remains a challenge till now. Here we introduce a combinational therapy of copper wires and pingyangmycin (bleomycin A5,PYM). Copper wires were retained in VMs by repeated penetration with a straight needle. Subsequently, PYM solution was injected into the lesion. Eight to 10 days later, copper wires were removed. The dressing was changed every day until the puncture pores healed. Magnetic resonance imaging scanning was performed to observe the change of VMs. From January 2001 to December 2011, 56 patients were treated. During the follow-up period, most of the VMs shrunk obviously. The symptoms were relieved or disappeared. The complications included local pain, temporary paraesthesia and moderate fever, which disappeared quickly after the removal of copper wires. This combinational therapy is a safe and effective approach for the complex VMs in soft tissue.

Management of orbital emphysema secondary to rhegmatogenous retinal detachment repair with hyperbaric oxygen therapy.

PubMed

Iniesta-Sanchez, Dante L; Romero-Caballero, Fatima; Aguirre-Alvarado, Adriana; Rebollo-Hurtado, Victoria; Velez-Montoya, Raul

2016-04-01

To describe the case of orbital subcutaneous emphysema who was successfully treated with hyperbaric oxygen therapy. Case report. Retrospective analysis of medical records and computer tomography images. A 40 years-old female, with retinal detachment who was seen at the emergency department, two weeks after undergoing a combined procedure of pars plana vitrectomy, scleral buckle and Sulfur hexafluoride tamponade. The patient complained of pain, decrease eye movement and edema of the upper eyelid. Clinical examination revealed periorbital crepitus. She was treated immediately with soft tissue decompression with small-gauge needle. Orbital emphysema recurred quickly, indicating possible gas trapped in the soft tissue. Using the US NAVY decompression protocol we were able to achieve fast clinical improvement. The protocol was repeated in several occasions until complete resolution. Hyperbaric oxygen therapy is an effective treatment for orbital and periorbital emphysema, due to its property of helping accelerate N 2 elimination from adipose tissue.

The Application of Tensegrity Massage in a Professionally Active Musician - Case Report.

PubMed

Wilk, Iwona; Kurpas, Donata; Andrzejewski, Waldemar; Okręglicka-Forysiak, Ewa; Gworys, Bohdan; Kassolik, Krzysztof

2016-01-01

The purpose of our study was to present options for the application of tensegrity massage to manage pain caused by the overload of soft tissues in musicians. Tensegrity massage was applied to a 34-year-old male violinist. The methodology included a correct positioning and tensegrity massage with individually designed procedure. After therapy, the patient achieved complete pain relief, and relaxation of muscles in the shoulder girdle and free part of the upper arm. The analgesic effect lasted for 6 months after the end of therapy. Massage is an effective method in eliminating pain caused by the overload of soft tissues. If used regularly before physical effort, it can prevent muscle overload. The presented massage procedure is an effective therapy in pain caused by the overload of soft tissues in musicians and it can be one of the elements of complex physiotherapy in active musicians. © 2014 Association of Rehabilitation Nurses.

Interstitial ablation and imaging of soft tissue using miniaturized ultrasound arrays

NASA Astrophysics Data System (ADS)

Makin, Inder R. S.; Gallagher, Laura A.; Mast, T. Douglas; Runk, Megan M.; Faidi, Waseem; Barthe, Peter G.; Slayton, Michael H.

2004-05-01

A potential alternative to extracorporeal, noninvasive HIFU therapy is minimally invasive, interstitial ultrasound ablation that can be performed laparoscopically or percutaneously. Research in this area at Guided Therapy Systems and Ethicon Endo-Surgery has included development of miniaturized (~3 mm diameter) linear ultrasound arrays capable of high power for bulk tissue ablation as well as broad bandwidth for imaging. An integrated control system allows therapy planning and automated treatment guided by real-time interstitial B-scan imaging. Image quality, challenging because of limited probe dimensions and channel count, is aided by signal processing techniques that improve image definition and contrast. Simulations of ultrasonic heat deposition, bio-heat transfer, and tissue modification provide understanding and guidance for development of treatment strategies. Results from in vitro and in vivo ablation experiments, together with corresponding simulations, will be described. Using methods of rotational scanning, this approach is shown to be capable of clinically relevant ablation rates and volumes.

Clinical implications of basic science discoveries: induced pluripotent stem cell therapy in transplantation--a potential role for immunologic tolerance.

PubMed

Wertheim, J A; Leventhal, J R

2015-04-01

Induced pluripotent stem cells (iPSCs) hold the potential for future development of genetically identical tissues from almost any mature cell lineage. For clinical applications in cell therapy and transplantation, it may provide a means to one-day restore dysfunctional or damaged tissue without the need for immunosuppression. A recent study by de Almeida et al published in the journal Nature Communications indicates that iPSCs may indeed elicit an immune response that evolves as cells differentiate toward maturity to induce a state of tolerance within a recipient animal. If these early findings hold true, it suggests a possible explanation for self-recognition of mature cells derived from iPSCs for use in future therapeutic interventions in transplantation such as cellular therapy or tissue engineering. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Regenerative photonic therapy: Review

NASA Astrophysics Data System (ADS)

Salansky, Natasha; Salansky, Norman

2012-09-01

After four decades of research of photobiomodulation phenomena in mammals in vitro and in vivo, a solid foundation is created for the use of photobiomodulation in regenerative medicine. Significant accomplishments are achieved in animal models that demonstrate opportunities for photo-regeneration of injured or pathological tissues: skin, muscles and nerves. However, the use of photobiomodulation in clinical studies leads to controversial results while negative or marginal clinical efficacy is reported along with positive findings. A thor ough analysis of requirements to the optical parameters (dosimetry) for high efficacy in photobimodulation led us to the conclusion that there are several misconceptions in the clinical applications of low level laser therapy (LLLT). We present a novel appr oach of regenerative photonic therapy (RPT) for tissue healing and regeneration that overcomes major drawbacks of LLLT. Encouraging clinical results on RPT efficacy are presented. Requirements for RPT approach and vision for its future development for tissue regeneration is discussed.

[POSSIBILITIES OF VACUUM THERAPY APPLICATION IN DISORDERS OF VENOUS OUTFLOW IN ISLET GRAFTS].

PubMed

Badyul, P O; Samoylenko, G E; Nor, N M; Slesarenko, K S

2015-07-01

The experience of "distressed" (problematic) flaps application in 33 patients with soft tissue defects over 2010-2014 years were analysed. It was proposed to use the local negative pressure for the prevention and treatment of complications associated with venous insufficiency or trombosis in using of plastics with vascularised complexes of tissues. Vacuum-therapy was conducted with the help of negative pressure apparatus "AGATE-Dnepr" (Ukraine) by attaching silver-containing polyurethane sponge on the operating zone, covering the flap with the surrounding skin netting band "Grassolind". The recommended standard of negative pressure of 75-125 mm Hg, both in impulse and in continuous mode was used. The high efficiency of vacuum-therapy for survival of grafts has been demonstrated. Thus, it might be considered as an effective element of prevention and treatment of complications associated with venous insufficiency or trombosis using of vascularised tissue complex plastics of defects.

Open tibial fractures grade IIIC treated successfully with external fixation, negative-pressure wound therapy and recombinant human bone morphogenetic protein 7.

PubMed

Babiak, Ireneusz

2014-10-01

The aim of the therapy in open tibial fractures grade III was to cover the bone with soft tissue and achieve healed fracture without persistent infection. Open tibial fractures grade IIIC with massive soft tissue damage require combined orthopaedic, vascular and plastic-reconstructive procedures. Negative-pressure wound therapy (NPWT), used in two consecutive cases with open fracture grade IIIC of the tibia diaphysis, healed extensive soft tissue defect with exposure of the bone. NPWT eventually allowed for wound closure by split skin graft within 21-25 days. Ilizarov external fixator combined with application of recombinant human bone morphogenetic protein-7 at the site of delayed union enhanced definitive bone healing within 16-18 months. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Wound bed preparation: A novel approach using HydroTherapy.

PubMed

Atkin, Leanne; Ousey, Karen

2016-12-01

Wounds that fail to heal quickly are often encountered by community nursing staff. An important step in assisting these chronic or stalled wounds progress through healing is debridement to remove devitalised tissue, including slough and eschar, that can prevent the wound from healing. A unique wound treatment called HydroTherapy aims to provide an optimal healing environment. The first step of HydroTherapy involves HydroClean plus™, this dressing enables removal of devitalised tissue through autolytic debridement and absorption of wound fluid. Irrigation and cleansing provided by Ringer's solution from the dressing further removes any necrotic tissue or eschar. Once effective wound bed preparation has been achieved a second dressing, HydroTac™, provides an ongoing hydrated wound environment that enables re-epithelialisation to occur in an unrestricted fashion. This paper presents 3 case studies of slow healing wounds treated with HydroClean plus™ which demonstrates effective wound debridement.

Gene therapy in plastic surgery.

PubMed

Tepper, Oren M; Mehrara, Babak J

2002-02-01

Recent developments in gene therapy have shown promise in the treatment of soft-tissue repair, bone formation, nerve regeneration, and cranial suture development. This special topic article reviews commonly used methods of gene therapy and discusses their various advantages and disadvantages. In addition, an overview of new developments in gene therapy as they relate to plastic surgery is provided.

Focusing light through biological tissue and tissue-mimicking phantoms up to 9.6 cm in thickness with digital optical phase conjugation

NASA Astrophysics Data System (ADS)

Shen, Yuecheng; Liu, Yan; Ma, Cheng; Wang, Lihong V.

2016-08-01

Optical phase conjugation (OPC)-based wavefront shaping techniques focus light through or within scattering media, which is critically important for deep-tissue optical imaging, manipulation, and therapy. However, to date, the sample thickness in OPC experiments has been limited to only a few millimeters. Here, by using a laser with a long coherence length and an optimized digital OPC system that can safely deliver more light power, we focused 532-nm light through tissue-mimicking phantoms up to 9.6 cm thick, as well as through ex vivo chicken breast tissue up to 2.5 cm thick. Our results demonstrate that OPC can be achieved even when photons have experienced on average 1000 scattering events. The demonstrated penetration of nearly 10 cm (˜100 transport mean free paths) has never been achieved before by any optical focusing technique, and it shows the promise of OPC for deep-tissue noninvasive optical imaging, manipulation, and therapy.

Regenerative Repair of Damaged Meniscus with Autologous Adipose Tissue-Derived Stem Cells

PubMed Central

Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

2014-01-01

Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee. PMID:24592390

The hopes and fears of in utero gene therapy for genetic disease--a review.

PubMed

Coutelle, C; Themis, M; Waddington, S; Gregory, L; Nivsarkar, M; Buckley, S; Cook, T; Rodeck, C; Peebles, D; David, A

2003-10-01

Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease. It is based on the concept that application of gene therapy vectors to the fetus in utero may prevent the development of early disease related tissue damage, may allow targeting of otherwise inaccessible organs, tissues and still expanding stem cell populations and may also provide postnatal tolerance against the therapeutic transgenic protein. This review outlines the hypothesis and scientific background of in utero gene therapy and addresses some of the frequently expressed concerns raised by this still experimental, potentially preventive gene therapy approach. We describe and discuss the choice of vectors, of animal models and routes of administration to the fetus. We address potential risk factors of prenatal gene therapy such as vector toxicity, inadvertent germ line modification, developmental aberration and oncogenesis as well as specific risks of this procedure for the fetus and mother and discuss their ethical implications.

SU-E-T-470: Importance of HU-Mass Density Calibration Technique in Proton Pencil Beam Dose Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penfold, S; Miller, A

2015-06-15

Purpose: Stoichiometric calibration of Hounsfield Units (HUs) for conversion to proton relative stopping powers (RStPs) is vital for accurate dose calculation in proton therapy. However proton dose distributions are not only dependent on RStP, but also on relative scattering power (RScP) of patient tissues. RScP is approximated from material density but a stoichiometric calibration of HU-density tables is commonly neglected. The purpose of this work was to quantify the difference in calculated dose of a commercial TPS when using HU-density tables based on tissue substitute materials and stoichiometric calibrated ICRU tissues. Methods: Two HU-density calibration tables were generated based onmore » scans of the CIRS electron density phantom. The first table was based directly on measured HU and manufacturer quoted density of tissue substitute materials. The second was based on the same CT scan of the CIRS phantom followed by a stoichiometric calibration of ICRU44 tissue materials. The research version of Pinnacle{sup 3} proton therapy was used to compute dose in a patient CT data set utilizing both HU-density tables. Results: The two HU-density tables showed significant differences for bone tissues; the difference increasing with increasing HU. Differences in density calibration table translated to a difference in calculated RScP of −2.5% for ICRU skeletal muscle and 9.2% for ICRU femur. Dose-volume histogram analysis of a parallel opposed proton therapy prostate plan showed that the difference in calculated dose was negligible when using the two different HU-density calibration tables. Conclusion: The impact of HU-density calibration technique on proton therapy dose calculation was assessed. While differences were found in the calculated RScP of bony tissues, the difference in dose distribution for realistic treatment scenarios was found to be insignificant.« less

Targeted therapies in cancer - challenges and chances offered by newly developed techniques for protein analysis in clinical tissues

PubMed Central

Malinowsky, K; Wolff, C; Gündisch, S; Berg, D; Becker, KF

2011-01-01

In recent years, new anticancer therapies have accompanied the classical approaches of surgery and radio- and chemotherapy. These new forms of treatment aim to inhibit specific molecular targets namely altered or deregulated proteins, which offer the possibility of individualized therapies. The specificity and efficiency of these new approaches, however, bring about a number of challenges. First of all, it is essential to specifically identify and quantify protein targets in tumor tissues for the reasonable use of such targeted therapies. Additionally, it has become even more obvious in recent years that the presence of a target protein is not always sufficient to predict the outcome of targeted therapies. The deregulation of downstream signaling molecules might also play an important role in the success of such therapeutic approaches. For these reasons, the analysis of tumor-specific protein expression profiles prior to therapy has been suggested as the most effective way to predict possible therapeutic results. To further elucidate signaling networks underlying cancer development and to identify new targets, it is necessary to implement tools that allow the rapid, precise, inexpensive and simultaneous analysis of many network components while requiring only a small amount of clinical material. Reverse phase protein microarray (RPPA) is a promising technology that meets these requirements while enabling the quantitative measurement of proteins. Together with recently developed protocols for the extraction of proteins from formalin-fixed, paraffin-embedded (FFPE) tissues, RPPA may provide the means to quantify therapeutic targets and diagnostic markers in the near future and reliably screen for new protein targets. With the possibility to quantitatively analyze DNA, RNA and protein from a single FFPE tissue sample, the methods are available for integrated patient profiling at all levels of gene expression, thus allowing optimal patient stratification for individualized therapies. PMID:21197262

Effects of acupuncture therapy on abdominal fat and hepatic fat content in obese children: a magnetic resonance imaging and proton magnetic resonance spectroscopy study.

PubMed

Zhang, Hong; Peng, Yun; Liu, ZuXiang; Li, Shilian; Lv, Zhongli; Tian, LiFang; Zhu, Jie; Zhao, XuNa; Chen, Min

2011-05-01

The aim of this study was to use magnetic resonance imaging (MRI) together with proton magnetic resonance spectroscopy ((1)H-MRS) to study the influence of acupuncture therapy on abdominal fat and hepatic fat content in obese children. The design was a longitudinal, clinical intervention study of acupuncture therapy. SUBJECTS were 10 healthy, obese children (age: 11.4 ± 1.65 years, body-mass index [BMI]: 29.03 ± 4.81 kg/m(2)). Measurements included various anthropometric parameters, abdominal fat (assessed by MRI) and hepatic fat content (assessed by (1)H-MRS) at baseline and after 1 month of acupuncture therapy. One (1) month of acupuncture therapy significantly reduced the subjects' BMI by 3.5% (p = 0.005), abdominal visceral adipose tissue (VAT) volume by 16.04% (p < 0.0001), abdominal total adipose tissue volume by 10.45% (p = 0.001), and abdominal visceral to subcutaneous fat ratio by 10.59% (p = 0.007). Decreases in body weight (-2.13%), waist circumference (-1.44%), hip circumference (-0.33%), waist-to-hip ratio (WHR) (-0.99%), abdominal subcutaneous adipose tissue (SAT) volume (-5.63%), and intrahepatic triglyceride (IHTG) content (-9.03%) were also observed, although these were not significant (p > 0.05). There was a significant correlation between the level of abdominal fat (SAT, VAT) and anthropometric parameters (weight, BMI, waist circumferences, hip circumferences). There was no statistically significant correlation between IHTG and anthropometric parameters or abdominal fat content. The first direct experimental evidence is provided demonstrating that acupuncture therapy significantly reduces BMI and abdominal adipose tissue by reducing abdominal VAT content without significant changes in body weight, waist circumference, hip circumference, WHR, abdominal SAT, or IHTG content. Thus, the use of acupuncture therapy to selectively target a reduction in abdominal VAT content should become more important and more popular in the future.

Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy.

PubMed

Li, Kuei-Chang; Hu, Yu-Chen

2015-05-01

Diseases in articular cartilages affect millions of people. Despite the relatively simple biochemical and cellular composition of articular cartilages, the self-repair ability of cartilage is limited. Successful cartilage tissue engineering requires intricately coordinated interactions between matrerials, cells, biological factors, and phycial/mechanical factors, and still faces a multitude of challenges. This article presents an overview of the cartilage biology, current treatments, recent advances in the materials, biological factors, and cells used in cartilage tissue engineering/regeneration, with strong emphasis on the perspectives of gene regulation (e.g., microRNA) and gene therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rejuvenating Strategies for Stem Cell-based Therapies in Aging

PubMed Central

Neves, Joana; Sousa-Victor, Pedro; Jasper, Heinrich

2017-01-01

SUMMARY Recent advances in our understanding of tissue regeneration and the development of efficient approaches to induce and differentiate pluripotent stem cells for cell replacement therapies promise exciting avenues for treating degenerative age-related diseases. However, clinical studies and insights from model organisms have identified major roadblocks that normal aging processes impose on tissue regeneration. These new insights suggest that specific targeting of environmental niche components, including growth factors, ECM and immune cells, and intrinsic stem cell properties that are affected by aging will be critical for development of new strategies to improve stem cell function and optimize tissue repair processes. PMID:28157498

Proton beams in radiotherapy

NASA Astrophysics Data System (ADS)

Khoroshkov, V. S.; Minakova, E. I.

1998-11-01

A branch of radiology, proton therapy employs fast protons as a tool for the treatment of various, mainly oncological, diseases. The features of tissue ionization by protons (Bragg peak) facilitate a further step towards solving the principal challenge in radiology: to deliver a sufficiently high and homogeneous dose to virtually any tumour, while sparing healthy neighbouring tissues, organs and structures. The state of the art of proton therapy is described, as well as the main technical, physics and clinical results gained since the 1950s at high-energy physics centres worldwide. The future of proton therapy is connected with the construction of hospital-based facilities with dedicated medical accelerators and modern technical instrumentation.

Microplasma radiofrequency technology combined with triamcinolone improved the therapeutic effect on Chinese patients with hypertrophic scar and reduced the risk of tissue atrophy.

PubMed

Yu, Shui; Li, Hengjin

2016-01-01

The current study aimed to assess the value of microplasma radiofrequency technology combined with triamcinolone for the therapy of Chinese patients with hypertrophic scar. A total of 120 participants with hypertrophic scars were enrolled in the current study. Participants were divided into two groups based on sex, and then randomly and evenly divided into four groups (Groups A, B, C, and D). Participants in Group A received microplasma radiofrequency technology combined with triamcinolone. Participants in Group B received microplasma radiofrequency technology combined with normal saline. Participants in Groups C and D received triamcinolone (40 and 10 mg/mL) injected directly into scar. Experienced physicians evaluated the condition of scars according to the Vancouver Scar Scale 1 month before and after the therapy. There was no difference in age, sex, area, height and location of scars, and Vancouver Scar Scale scores before the therapy between any groups (P>0.05 for all). Vancouver Scar Scale scores after the therapy were significantly lower than those before the therapy in all groups (P<0.05 for all). Vancouver Scar Scale scores after the therapy in Group A were significantly lower than those after the therapy in Groups B and C (P<0.05 for all). Vancouver Scar Scale scores after the therapy in Group B were significantly higher than those after the therapy in Group C (P<0.05 for all) and similar to those after the therapy in Group D (P>0.05 for all). Incidences of tissue atrophy after the therapy were significantly lower in Groups A and B than in Group C (P<0.05 for all) and similar among Groups A, B, and D (P>0.05 for all). Microplasma radiofrequency technology combined with triamcinolone improved the therapeutic effect on Chinese patients with hypertrophic scar and reduced the risk of tissue atrophy compared with the use of either microplasma radiofrequency technology or triamcinolone injection alone.

Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy

PubMed Central

Chen, Rui; Zhang, Luzhong; Gao, Jian; Wu, Wei; Hu, Yong; Jiang, Xiqun

2011-01-01

Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource. PMID:21765637

Association of Electrochemical Therapy With Optical, Mechanical, and Acoustic Impedance Properties of Porcine Skin.

PubMed

Moy, Wesley J; Su, Erica; Chen, Jason J; Oh, Connie; Jing, Joe C; Qu, Yueqiao; He, Youmin; Chen, Zhongping; Wong, Brian J F

2017-12-01

The classic management of burn scars and other injuries to the skin has largely relied on soft-tissue transfer to resurface damaged tissue with local tissue transfer or skin graft placement. In situ generation of electrochemical reactions using needle electrodes and an application of current may be a new approach to treat scars and skin. To examine the changes in optical, mechanical, and acoustic impedance properties in porcine skin after electrochemical therapy. This preclinical pilot study, performed from August 1, 2015, to November 1, 2016, investigated the effects of localized pH-driven electrochemical therapy of ex vivo porcine skin using 24 skin samples. Platinum-plated needle electrodes were inserted into fresh porcine skin samples. A DC power supply provided a voltage of 4 to 5 V with a 3-minute application time. Specimens were analyzed using optical coherence tomography, optical coherence elastography, and ultrasonography. Ultrasonography was performed under 3 conditions (n = 2 per condition), optical coherence tomography was performed under 2 conditions (n = 2 per condition), and optical coherence elastography was performed under 2 conditions (n = 2 per condition). The remaining samples were used for the positive and negative control groups (n = 10). Platinum-plated needle electrodes were inserted into fresh porcine skin samples. A DC power supply provided a voltage of 4 to 5 V with a 3-minute application. Tissue softening was observed at the anode and cathode sites as a result of electrochemical modification. Volumetric changes were noted using each optical and acoustic technique. A total of 24 ex vivo porcine skin samples were used for this pilot study. Optical coherence tomography measured spatial distribution of superficial tissue changes around each electrode site. At 4 V for 3 minutes, a total volumetric effect of 0.47 mm3 was found at the anode site and 0.51 mm3 at the cathode site. For 5 V for 3 minutes, a total volumetric effect of 0.85 mm3 was found at the anode site and 1.05 mm3 at the cathode site. Electrochemical therapy is a low-cost technique that is on par with the costs of suture and scalpel. The use of electrochemical therapy to create mechanical and physiologic changes in tissue has the potential to locally remodel the soft-tissue matrix, which ultimately may lead to an inexpensive scar treatment or skin rejuvenation therapy. NA.

Thermal distribution in biological tissue at laser induced fluorescence and photodynamic therapy

NASA Astrophysics Data System (ADS)

Krasnikov, I. V.; Seteikin, A. Yu.; Drakaki, E.; Makropoulou, M.

2012-03-01

Laser induced fluorescence spectroscopy and photodynamic therapy (PDT) are techniques currently introduced in clinical applications for visualization and local destruction of malignant tumours as well as premalignant lesions. During the laser irradiation of tissues for the diagnostic and therapeutic purposes, the absorbed optical energy generates heat, although the power density of the treatment light for surface illumination is normally low enough not to cause any significantly increased tissue temperature. In this work we tried to evaluate the utility of Monte Carlo modeling for simulating the temperature fields and the dynamics of heat conduction into the skin tissue under several laser irradiation conditions with both a pulsed UV laser and a continuous wave visible laser beam. The analysis of the results showed that heat is not localized on the surface, but it is collected inside the tissue. By varying the boundary conditions on the surface and the type of the laser radiation (continuous or pulsed) we can reach higher than normal temperature inside the tissue without simultaneous formation of thermally damaged tissue (e.g. coagulation or necrosis zone).

Negative-pressure Wound Therapy in Chronic Inflammatory Breast Diseases

PubMed Central

Namdaroğlu, Ozan Barış; Yazıcı, Hilmi; Öztürk, Ahmet Mücteba; Yakan, Savaş; Yıldırım, Mehmet; Uçar, Ahmet Deniz; Erkan, Nazif

2016-01-01

Mastitis is inflammation of breast tissue that may or may not originate from an infection. Two different forms of mastitis have been described, lactational and non-lactational. Lactational mastitis is the most common type and generally conservative therapy that includes milk removal and physical therapy provides symptomatic relief, but antibiotic therapy is also needed. Common types of non-lactational mastitis are periductal mastitis and idiopathic granulomatous mastitis. Treatment includes antibiotics, drainage, and surgery, but usually this is a chronic process and a therapeutic management algorithm for chronic breast inflammation is unclear and has no consensus. Negative-pressure wound therapy is commonly used for various types of wounds but is limited for breast wounds. In this report, we present and discuss two patients with chronic breast inflammation who underwent surgery and were successfully treated using negative-pressure wound therapy to minimize wide tissue defects and cosmetic problems after surgery. Use of negative-pressure wound therapy for breast wounds might be benefical as it is with other wounds but there is scarce information in the literature PMID:28331742

Effects of topical oxygen therapy on ischemic wound healing.

PubMed

Rao, Congqiang; Xiao, Liling; Liu, Hongwei; Li, Shenghong; Lu, Jinqiang; Li, Jiangxuan; Gu, Shixing

2016-01-01

[Purpose] This study evaluated the effects of topical oxygen therapy on the hind limb wounds of rats under ischemic conditions. [Subjects and Methods] Twelve injured rats were treated with topical oxygen on skin wounds located on the hind limb and compared with twelve injured control rats. Indexes including gross morphology of the wound, wound healing time, wound healing rate, and histological and immunohistochemical staining of sections of wound tissue were examined at different time points after intervention. [Results] The wound healing time was shorter in the topical oxygen therapy group than the control group. The wound healing rate and granulation tissue formation in the topical oxygen therapy group showed significant improvement on days 3, 7, and 14. Through van Gieson staining, the accumulation of collagen fiber in the topical oxygen therapy group was found to have improved when compared with the control group on day 7. Through semiquantitative immunohistochemical staining, many more new vessels were found in the topical oxygen therapy group compared with the model control group on day 7. [Conclusion] The results of the experiment showed that topical oxygen therapy improved ischemic wound healing.

A Micro-Thermal Sensor for Focal Therapy Applications

NASA Astrophysics Data System (ADS)

Natesan, Harishankar; Hodges, Wyatt; Choi, Jeunghwan; Lubner, Sean; Dames, Chris; Bischof, John

2016-02-01

There is an urgent need for sensors deployed during focal therapies to inform treatment planning and in vivo monitoring in thin tissues. Specifically, the measurement of thermal properties, cooling surface contact, tissue thickness, blood flow and phase change with mm to sub mm accuracy are needed. As a proof of principle, we demonstrate that a micro-thermal sensor based on the supported “3ω” technique can achieve this in vitro under idealized conditions in 0.5 to 2 mm thick tissues relevant to cryoablation of the pulmonary vein (PV). To begin with “3ω” sensors were microfabricated onto flat glass as an idealization of a focal probe surface. The sensor was then used to make new measurements of ‘k’ (W/m.K) of porcine PV, esophagus, and phrenic nerve, all needed for PV cryoabalation treatment planning. Further, by modifying the sensor use from traditional to dynamic mode new measurements related to tissue vs. fluid (i.e. water) contact, fluid flow conditions, tissue thickness, and phase change were made. In summary, the in vitro idealized system data presented is promising and warrants future work to integrate and test supported “3ω” sensors on in vivo deployed focal therapy probe surfaces (i.e. balloons or catheters).

Stages of Retinoblastoma

MedlinePlus

... internal radiation therapy may include the following: Plaque radiotherapy : Radioactive seeds are attached to one side of ... other nearby tissue from the radiation. Enlarge Plaque radiotherapy of the eye. A type of radiation therapy ...

Feasibility of Image-Guided Transthoracic Core Needle Biopsy in the BATTLE Lung Trial

PubMed Central

Tam, Alda L.; Kim, Edward S.; Lee, J. Jack; Ensor, Joe E.; Hicks, Marshall E.; Tang, Ximing; Blumenschein, George R.; Alden, Christine M.; Erasmus, Jeremy J.; Tsao, Anne; Lippman, Scott M.; Hong, Waun K.; Wistuba, Ignacio I.; Gupta, Sanjay

2013-01-01

Purpose As therapy for non-small cell lung cancer (NSCLC) patients becomes more personalized, additional tissue in the form of core needle biopsies (CNBs) for biomarker analysis is increasingly required for determining appropriate treatment and for enrollment into clinical trials. We report our experience with small-caliber percutaneous transthoracic (PT) CNBs for the evaluation of multiple molecular biomarkers in BATTLE (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination), a personalized, targeted therapy NSCLC clinical trial. Methods The medical records of patients who underwent PTCNB for consideration of enrollment in BATTLE, were reviewed for diagnostic yield of 11 predetermined molecular markers, and procedural complications. Univariate and multivariate analyses of factors related to patient and lesion characteristics were performed to determine possible influences on diagnostic yield. Results One hundred and seventy PTCNBs were performed using 20-gauge biopsy needles in 151 NSCLC patients screened for the trial. 82.9% of the biopsy specimens were found to have adequate tumor tissue for analysis of the required biomarkers. On multivariate analysis, metastatic lesions were 5.4 times more likely to yield diagnostic tissue as compared to primary tumors (p = 0.0079). Pneumothorax and chest tube insertion rates were 15.3% and 9.4%, respectively. Conclusions Image-guided 20-gauge PTCNB is safe and provides adequate tissue for analysis of multiple biomarkers in the majority of patients being considered for enrollment into a personalized, targeted therapy NSCLC clinical trial. Metastatic lesions are more likely to yield diagnostic tissue as compared to primary tumors. PMID:23442309

Near "real" time magnetic resonance images as a monitoring system for interstitial laser therapy: experimental protocols

NASA Astrophysics Data System (ADS)

Castro, Dan J.; Farahani, Keyvan; Soudant, Jacques; Zwarun, Andrew A.; Lufkin, Robert B.

1992-06-01

The failure rate of cancer treatment remains unacceptably high, still being a leading cause of mortality in adults and children despite major advances over the past 50 years in the fields of surgery, radiation therapy and, more recently, chemo and immunotherapy. Surgical access to some deep tumors of the head and neck and other areas often require extensive dissections with residual functional and cosmetic deformities. Repeated treatment is not possible after maximum dose radiotherapy and chemotherapy is still limited by its systemic toxicity. An attractive solution to these problems would be the development of a new adjunctive method combining the best features of interstitial laser therapy for selective tumor destruction via minimally invasive techniques for access and 3-D magnetic resonance imaging (MRI) as a monitoring system for laser-tissue interactions. Interstitial laser therapy (ILT) via fiberoptics allow laser energy to be delivered directly into deeper tissues. However, this concept will become clinically useful only when noninvasive, accurate, and reproducible monitoring methods are developed to measure energy delivery to tissues. MRI has numerous advantages in evaluating the irreversible effects of laser treatment in tissues, since laser energy includes changes not only in the thermal motions of hydrogen protons within the tissue, but also in the distribution and mobility of water and lipids. These techniques should greatly improve the use of ILT in combination with MRI to allow treatment of deeper, more difficult to reach tumors of head and neck and other anatomical areas with a single needle stick.

Allograft integration in a rabbit transgenic model for anterior cruciate ligament reconstruction.

PubMed

Bachy, M; Sherifi, I; Zadegan, F; Petite, H; Vialle, R; Hannouche, D

2016-04-01

Tissue engineering strategies include both cell-based and cell homing therapies. Ligamentous tissues are highly specialized and constitute vital components of the musculoskeletal system. Their damage causes significant morbidity and loss in function. The aim of this study is to analyze tendinous graft integration, cell repopulation and ligamentization by using GFP+/- allografts in GFP+/- transgenic New Zealand white (NZW) rabbits. Graft implantation was designed to closely mimic anterior cruciate ligament (ACL) repair surgery. Allografts were implanted in 8 NZW rabbits and assessed at 5 days, 3 weeks and 6 weeks through: (1) arthroCT imaging, (2) morphological analysis of the transplanted allograft, (3) histological analysis, (4) collagen type I immunochemistry, and (5) GFP cell tracking. Collagen remodeling was appreciated at 3 and 6 weeks. Graft repopulation with host cells, chondrocyte-like cells at the tendon-bone interface and graft corticalization in the bone tunnels were noticed at 3 weeks. By contrast we noticed a central necrosis aspect in the allografts intra-articularly at 6 weeks with a cell migration towards the graft edge near the synovium. Our study has served to gain a better understanding of tendinous allograft bone integration, ligamentization and allograft repopulation. We believe that both cell-based therapies and cell homing therapies are beneficial in ligament tissue engineering. Future studies may elucidate whether cell repopulation occurs with pre-differentiated or progenitor cells. We believe that both cell-based therapies and cell homing therapies are beneficial in ligament tissue engineering. Level V (animal study). Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A new low-cost negative-pressure wound therapy versus a commercially available therapy device widely used to treat complex traumatic injuries: a prospective, randomized, non-inferiority trial.

PubMed

Kamamoto, Fabio; Lima, Ana Lucia Munhoz; Rezende, Marcelo Rosa de; Mattar-Junior, Rames; Leonhardt, Marcos de Camargo; Kojima, Kodi Edson; Santos, Carla Chineze Dos

2017-12-01

Negative-pressure wound therapy has been widely adopted to reduce the complexity of treating a broad range of acute and chronic wounds. However, its cost is high. The objective of this study was to evaluate the following two different methods of negative-pressure wound therapy in terms of healing time: a low-cost method of negative-pressure wound therapy (a pressure stabilizer device connected to a hospital wall-vacuum system with a gauze-sealed dressing, USP) and the standard of care (vacuum-assisted closure, VAC). This is a randomized, controlled, non-inferiority, unblinded trial. Patients admitted with complex injuries to a trauma center in a public referral hospital who were indicated for orthopedic surgery were randomized to a USP or VAC group. The primary outcome was the time required to achieve a "ready for surgery condition", which was defined as a wound bed with healthy granulation tissue and without necrosis or purulent secretion. Wound bed area contraction, granulation tissue growth and the direct costs of the dressings were secondary outcomes. Variation in area and granulation tissue growth were essentially the same between the systems, and healing time was equal between the groups (p=0.379). In both systems, serial debridement increased wound area (p=0.934), and granulation tissue was also increased (p=0.408). The mean treatment cost was US$ 15.15 in the USP group and US$ 872.59 in the VAC group. For treating complex traumatic injuries, USP was non-inferior to and less expensive than VAC.

Optical properties of mice skin for optical therapy relevant wavelengths: influence of gender and pigmentation

NASA Astrophysics Data System (ADS)

Sabino, C. P.; Deana, A. M.; Silva, D. F. T.; França, C. M.; Yoshimura, T. M.; Ribeiro, M. S.

2015-03-01

Red and near-infrared light have been widely employed in optical therapies. Skin is the most common optical barrier in non-invasive techniques and in many cases it is the target tissue itself. Consequently, to optimize the outcomes brought by lightbased therapies, the optical properties of skin tissue must be very well elucidated. In the present study, we evaluated the dorsal skin optical properties of albino (BALB/c) and pigmented (C57BL/6) mice using the Kubelka-Munk photon transport model. We evaluated samples from male and female young mice of both strains. Analysis was performed for wavelengths at 630, 660, 780, 810 and 905 nm due to their prevalent use in optical therapies, such as low-level light (or laser) and photodynamic therapies. Spectrophotometric measurements of diffuse transmittance and reflectance were performed using a single integrating sphere coupled to a proper spectrophotometer. Statistic analysis was made by two-way ANOVA, with Tukey as post-test and Levenne and Shapiro-Wilks as pre-tests. Statistical significance was considered when p<0.05. Our results show only a slight transmittance increment (<10 %) as wavelengths are increased from 630 to 905 nm, and no statistical significance was observed. Albino male mice present reduced transmittance levels for all wavelengths. The organization and abundance of skin composing tissues significantly influence its scattering optical properties although absorption remains constant. We conclude that factors such as subcutaneous adiposity and connective tissue structure can have statistically significant influence on mice skin optical properties and these factors have relevant variations among different gender and strains.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubin, R.L.; Doku, H.C.

In recent years, therapeutic radiology has been used extensively in the management of head and neck malignancies. An increasing number of the population who have been exposed to such therapy are being seen by the dentist for dental treatment. It is recognized that radiation therapy may cause temporary and permanent alterations in tissue. A discussion of the various therapeutic modalities and their side effects on the oral tissues has been presented to aid the dental practitioner in understanding the problems and care of such patients. (auth)

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

PubMed Central

Dickson, Patricia; Peinovich, Maryn; McEntee, Michael; Lester, Thomas; Le, Steven; Krieger, Aimee; Manuel, Hayden; Jabagat, Catherine; Passage, Merry; Kakkis, Emil D.

2008-01-01

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human α-l-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of α-l-iduronidase–specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9–44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases. PMID:18654665

Neurodegeneration in diabetic retinopathy: Potential for novel therapies.

PubMed

Barber, Alistair J; Baccouche, Basma

2017-10-01

The complex pathology of diabetic retinopathy (DR) affects both vascular and neural tissue. The characteristics of neurodegeneration are well-described in animal models but have more recently been confirmed in the clinical setting, mostly by using non-invasive imaging approaches such as spectral domain optical coherence tomography (SD-OCT). The most frequent observations report loss of tissue in the nerve fiber layer and inner plexiform layer, confirming earlier findings from animal models. In several cases the reduction in inner retinal layers is reported in patients with little evidence of vascular lesions or macular edema, suggesting that degenerative loss of neural tissue in the inner retina can occur after relatively short durations of diabetes. Animal studies also suggest that neurodegeneration leading to retinal thinning is not limited to cell death and tissue loss but also includes changes in neuronal morphology, reduced synaptic protein expression and alterations in neurotransmission, including changes in expression of neurotransmitter receptors as well as neurotransmitter release, reuptake and metabolism. The concept of neurodegeneration as an early component of DR introduces the possibility to explore alternative therapies to prevent the onset of vision loss, including neuroprotective therapies and drugs targeting individual neurotransmitter systems, as well as more general neuroprotective approaches to preserve the integrity of the neural retina. In this review we consider some of the evidence for progressive retinal neurodegeneration in diabetes, and explore potential neuroprotective therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.

PubMed

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy.

Periodontal tissue engineering strategies based on nonoral stem cells.

PubMed

Requicha, João Filipe; Viegas, Carlos Alberto; Muñoz, Fernando; Reis, Rui Luís; Gomes, Manuela Estima

2014-01-01

Periodontal disease is an inflammatory disease which constitutes an important health problem in humans due to its enormous prevalence and life threatening implications on systemic health. Routine standard periodontal treatments include gingival flaps, root planning, application of growth/differentiation factors or filler materials and guided tissue regeneration. However, these treatments have come short on achieving regeneration ad integrum of the periodontium, mainly due to the presence of tissues from different embryonic origins and their complex interactions along the regenerative process. Tissue engineering (TE) aims to regenerate damaged tissue by providing the repair site with a suitable scaffold seeded with sufficient undifferentiated cells and, thus, constitutes a valuable alternative to current therapies for the treatment of periodontal defects. Stem cells from oral and dental origin are known to have potential to regenerate these tissues. Nevertheless, harvesting cells from these sites implies a significant local tissue morbidity and low cell yield, as compared to other anatomical sources of adult multipotent stem cells. This manuscript reviews studies describing the use of non-oral stem cells in tissue engineering strategies, highlighting the importance and potential of these alternative stem cells sources in the development of advanced therapies for periodontal regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Treatment Option Overview (Retinoblastoma)

MedlinePlus

... internal radiation therapy may include the following: Plaque radiotherapy : Radioactive seeds are attached to one side of ... other nearby tissue from the radiation. Enlarge Plaque radiotherapy of the eye. A type of radiation therapy ...

Treatment Options for Retinoblastoma

MedlinePlus

... internal radiation therapy may include the following: Plaque radiotherapy : Radioactive seeds are attached to one side of ... other nearby tissue from the radiation. Enlarge Plaque radiotherapy of the eye. A type of radiation therapy ...

Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy.

PubMed

Macías, J; Japón, M A; Leal, M; Sáez, C; Pineda, J A; Segura, D I; Ortega, J; Lissen, E

2001-12-07

The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure. To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts > or = 500/microl. From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts > or = 500/microl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones. Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks. This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation.

PubMed

Girst, S; Marx, C; Bräuer-Krisch, E; Bravin, A; Bartzsch, S; Oelfke, U; Greubel, C; Reindl, J; Siebenwirth, C; Zlobinskaya, O; Multhoff, G; Dollinger, G; Schmid, T E; Wilkens, J J

2015-09-01

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Cryopreserved Dental Pulp Tissues of Exfoliated Deciduous Teeth Is a Feasible Stem Cell Resource for Regenerative Medicine

PubMed Central

Yamaza, Haruyoshi; Akiyama, Kentaro; Hoshino, Yoshihiro; Song, Guangtai; Kukita, Toshio; Nonaka, Kazuaki; Shi, Songtao; Yamaza, Takayoshi

2012-01-01

Human exfoliated deciduous teeth have been considered to be a promising source for regenerative therapy because they contain unique postnatal stem cells from human exfoliated deciduous teeth (SHED) with self-renewal capacity, multipotency and immunomodulatory function. However preservation technique of deciduous teeth has not been developed. This study aimed to evaluate that cryopreserved dental pulp tissues of human exfoliated deciduous teeth is a retrievable and practical SHED source for cell-based therapy. SHED isolated from the cryopreserved deciduous pulp tissues for over 2 years (25–30 months) (SHED-Cryo) owned similar stem cell properties including clonogenicity, self-renew, stem cell marker expression, multipotency, in vivo tissue regenerative capacity and in vitro immunomodulatory function to SHED isolated from the fresh tissues (SHED-Fresh). To examine the therapeutic efficacy of SHED-Cryo on immune diseases, SHED-Cryo were intravenously transplanted into systemic lupus erythematosus (SLE) model MRL/lpr mice. Systemic SHED-Cryo-transplantation improved SLE-like disorders including short lifespan, elevated autoantibody levels and nephritis-like renal dysfunction. SHED-Cryo amended increased interleukin 17-secreting helper T cells in MRL/lpr mice systemically and locally. SHED-Cryo-transplantation was also able to recover osteoporosis bone reduction in long bones of MRL/lpr mice. Furthermore, SHED-Cryo-mediated tissue engineering induced bone regeneration in critical calvarial bone-defect sites of immunocompromised mice. The therapeutic efficacy of SHED-Cryo transplantation on immune and skeletal disorders was similar to that of SHED-Fresh. These data suggest that cryopreservation of dental pulp tissues of deciduous teeth provide a suitable and desirable approach for stem cell-based immune therapy and tissue engineering in regenerative medicine. PMID:23251621

Regression and statistical shape model based substitute CT generation for MRI alone external beam radiation therapy from standard clinical MRI sequences.

PubMed

Ghose, Soumya; Greer, Peter B; Sun, Jidi; Pichler, Peter; Rivest-Henault, David; Mitra, Jhimli; Richardson, Haylea; Wratten, Chris; Martin, Jarad; Arm, Jameen; Best, Leah; Dowling, Jason A

2017-10-27

In MR only radiation therapy planning, generation of the tissue specific HU map directly from the MRI would eliminate the need of CT image acquisition and may improve radiation therapy planning. The aim of this work is to generate and validate substitute CT (sCT) scans generated from standard T2 weighted MR pelvic scans in prostate radiation therapy dose planning. A Siemens Skyra 3T MRI scanner with laser bridge, flat couch and pelvic coil mounts was used to scan 39 patients scheduled for external beam radiation therapy for localized prostate cancer. For sCT generation a whole pelvis MRI (1.6 mm 3D isotropic T2w SPACE sequence) was acquired. Patients received a routine planning CT scan. Co-registered whole pelvis CT and T2w MRI pairs were used as training images. Advanced tissue specific non-linear regression models to predict HU for the fat, muscle, bladder and air were created from co-registered CT-MRI image pairs. On a test case T2w MRI, the bones and bladder were automatically segmented using a novel statistical shape and appearance model, while other soft tissues were separated using an Expectation-Maximization based clustering model. The CT bone in the training database that was most 'similar' to the segmented bone was then transformed with deformable registration to create the sCT component of the test case T2w MRI bone tissue. Predictions for the bone, air and soft tissue from the separate regression models were successively combined to generate a whole pelvis sCT. The change in monitor units between the sCT-based plans relative to the gold standard CT plan for the same IMRT dose plan was found to be [Formula: see text] (mean  ±  standard deviation) for 39 patients. The 3D Gamma pass rate was [Formula: see text] (2 mm/2%). The novel hybrid model is computationally efficient, generating an sCT in 20 min from standard T2w images for prostate cancer radiation therapy dose planning and DRR generation.

Regression and statistical shape model based substitute CT generation for MRI alone external beam radiation therapy from standard clinical MRI sequences

NASA Astrophysics Data System (ADS)

Ghose, Soumya; Greer, Peter B.; Sun, Jidi; Pichler, Peter; Rivest-Henault, David; Mitra, Jhimli; Richardson, Haylea; Wratten, Chris; Martin, Jarad; Arm, Jameen; Best, Leah; Dowling, Jason A.

2017-11-01

In MR only radiation therapy planning, generation of the tissue specific HU map directly from the MRI would eliminate the need of CT image acquisition and may improve radiation therapy planning. The aim of this work is to generate and validate substitute CT (sCT) scans generated from standard T2 weighted MR pelvic scans in prostate radiation therapy dose planning. A Siemens Skyra 3T MRI scanner with laser bridge, flat couch and pelvic coil mounts was used to scan 39 patients scheduled for external beam radiation therapy for localized prostate cancer. For sCT generation a whole pelvis MRI (1.6 mm 3D isotropic T2w SPACE sequence) was acquired. Patients received a routine planning CT scan. Co-registered whole pelvis CT and T2w MRI pairs were used as training images. Advanced tissue specific non-linear regression models to predict HU for the fat, muscle, bladder and air were created from co-registered CT-MRI image pairs. On a test case T2w MRI, the bones and bladder were automatically segmented using a novel statistical shape and appearance model, while other soft tissues were separated using an Expectation-Maximization based clustering model. The CT bone in the training database that was most ‘similar’ to the segmented bone was then transformed with deformable registration to create the sCT component of the test case T2w MRI bone tissue. Predictions for the bone, air and soft tissue from the separate regression models were successively combined to generate a whole pelvis sCT. The change in monitor units between the sCT-based plans relative to the gold standard CT plan for the same IMRT dose plan was found to be 0.3%+/-0.9% (mean  ±  standard deviation) for 39 patients. The 3D Gamma pass rate was 99.8+/-0.00 (2 mm/2%). The novel hybrid model is computationally efficient, generating an sCT in 20 min from standard T2w images for prostate cancer radiation therapy dose planning and DRR generation.

Influence of Negative-Pressure Wound Therapy on Tissue Oxygenation in Diabetic Feet.

PubMed

Jung, Jae-A; Yoo, Ki-Hyun; Han, Seung-Kyu; Lee, Ye-Na; Jeong, Seong-Ho; Dhong, Eun-Sang; Kim, Woo-Kyung

2016-08-01

Negative-pressure wound therapy (NPWT) has become a common wound care treatment modality for a variety of wounds. Several previous studies have reported that NPWT increases blood flow in the wound bed. However, NPWT might decrease tissue oxygenation in the wound bed because the foam sponge of NPWT compresses the wound bed under the influence of the applied negative pressure. Adequate tissue oxygenation is an essential consideration during diabetic foot management, and the foot is more sensitive to ischemia than any other region. Furthermore, the issue as to whether NPWT reduces or increases tissue oxygenation in diabetic feet has never been correctly addressed. The aim of this study was to evaluate the influence of NPWT on tissue oxygenation in diabetic feet. Transcutaneous partial oxygen pressures (TcPO2) were measured to determine tissue oxygenation levels beneath NPWT dressings on 21 feet of 21 diabetic foot ulcer patients. A TcPO2 sensor was fixed at the tarsometatarsal area of contralateral unwounded feet. A suction pressure of -125 mm Hg was applied until TcPO2 reached a steady state. The TcPO2 values for diabetic feet were measured before, during, and after NPWT. The TcPO2 levels decreased significantly after applying NPWT in all patients. Mean TcPO2 values before, during, and after therapy were 44.6 (SD, 15.2), 6.0 (SD, 7.1), and 40.3 (SD, 16.4) mm Hg (P < .01), respectively. These results show that NPWT significantly reduces tissue oxygenation levels in diabetic feet.

Current regulatory issues in cell and tissue therapy.

PubMed

Burger, S R

2003-01-01

Cell-based therapies have grown dramatically in power and scope in recent years. Once limited to blood and BM transplantation, these therapies now encompass tissue repair and regeneration, metabolic support, gene replacement, and immune effector functions, with established and investigational clinical applications in disorders affecting nearly every tissue and organ system. The complexity and novel applications of human cells, tissues, and cellular and tissue-based products (HCT/Ps), however, present potential risks for adverse events. The US Food and Drug Administration, responding to these concerns, has established a tiered, risk-based regulatory structure, in which more rigorous controls and safeguards are required for products thought to pose increased risk. The proposed good tissue practices (GTP) rule and existing good manufacturing practices (GMP) requirements form the principal elements of this regulatory framework. The proposed GTPs are intended to prevent HCT/P contamination with infectious disease agents, and to ensure that these cells and tissues maintain their integrity and function. GMPs focus on production of safe, pure, and potent products, and entail a higher level of process control and product characterization. All HCT/Ps will be required to comply with GTPs. HCT/Ps considered to present greater risks of adverse events, however, will be subject to both GTPs and GMPs, and must obtain premarket approval using the Investigational New Drug (IND) mechanism established for biologics. Although these requirements will present significant challenges for clinician- investigators and laboratories producing HCT/Ps, the regulations fundamentally support good clinical care by increasing safety and control, and enable good science by improving the quality and reliability of data.

Craniofacial Wound Healing with Photobiomodulation Therapy: New Insights and Current Challenges.

PubMed

Arany, P R

2016-08-01

The fundamental pathophysiologic response for the survival of all organisms is the process of wound healing. Inadequate or lack of healing constitutes the etiopathologic basis of many oral and systemic diseases. Among the numerous efforts to promote wound healing, biophotonics therapies have shown much promise. Advances in photonic technologies and a better understanding of light-tissue interactions, from parallel biophotonics fields such as in vivo optical imaging and optogenetics, are spearheading their popularity in biology and medicine. Use of high-dose lasers and light devices in dermatology, ophthalmology, oncology, and dentistry are now popular for specific clinical applications, such as surgery, skin rejuvenation, ocular and soft tissue recontouring, and antitumor and antimicrobial photodynamic therapy. However, a less well-known clinical application is the therapeutic use of low-dose biophotonics termed photobiomodulation (PBM) therapy, which is aimed at alleviating pain and inflammation, modulating immune responses, and promoting wound healing and tissue regeneration. Despite significant volumes of scientific literature from clinical and laboratory studies noting the phenomenological evidence for this innovative therapy, limited mechanistic insights have prevented rigorous and reproducible PBM clinical protocols. This article briefly reviews current evidence and focuses on gaps in knowledge to identify potential paths forward for clinical translation with PBM therapy with an emphasis on craniofacial wound healing. PBM offers a novel opportunity to examine fundamental nonvisual photobiological processes as well as develop innovative clinical therapies, thereby presenting an opportunity for a paradigm shift from conventional restorative/prosthetic approaches to regenerative modalities in clinical dentistry. © International & American Associations for Dental Research 2016.

Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers.

PubMed

Chew, G L; Huo, C W; Huang, D; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M C; Hopper, J L; Britt, K; Henderson, M A; Haviv, I; Thompson, E W

2014-11-01

Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other pharmacologic interventions in a preclinical model of high MD.

Lung texture in serial thoracic CT scans: correlation with radiologist-defined severity of acute changes following radiation therapy

NASA Astrophysics Data System (ADS)

Cunliffe, Alexandra R.; Armato, Samuel G., III; Straus, Christopher; Malik, Renuka; Al-Hallaq, Hania A.

2014-09-01

This study examines the correlation between the radiologist-defined severity of normal tissue damage following radiation therapy (RT) for lung cancer treatment and a set of mathematical descriptors of computed tomography (CT) scan texture (‘texture features’). A pre-therapy CT scan and a post-therapy CT scan were retrospectively collected under IRB approval for each of the 25 patients who underwent definitive RT (median dose: 66 Gy). Sixty regions of interest (ROIs) were automatically identified in the non-cancerous lung tissue of each post-therapy scan. A radiologist compared post-therapy scan ROIs with pre-therapy scans and categorized each as containing no abnormality, mild abnormality, moderate abnormality, or severe abnormality. Twenty texture features that characterize gray-level intensity, region morphology, and gray-level distribution were calculated in post-therapy scan ROIs and compared with anatomically matched ROIs in the pre-therapy scan. Linear regression and receiver operating characteristic (ROC) analysis were used to compare the percent feature value change (ΔFV) between ROIs at each category of visible radiation damage. Most ROIs contained no (65%) or mild abnormality (30%). ROIs with moderate (3%) or severe (2%) abnormalities were observed in 9 patients. For 19 of 20 features, ΔFV was significantly different among severity levels. For 12 features, significant differences were observed at every level. Compared with regions with no abnormalities, ΔFV for these 12 features increased, on average, by 1.5%, 12%, and 30%, respectively, for mild, moderate, and severe abnormalitites. Area under the ROC curve was largest when comparing ΔFV in the highest severity level with the remaining three categories (mean AUC across features: 0.84). In conclusion, 19 features that characterized the severity of radiologic changes from pre-therapy scans were identified. These features may be used in future studies to quantify acute normal lung tissue damage following RT. Presented, in part at the IASLC 15th World Conference on Lung Conference, Sydney, AUS (2013).

[New possibilities will open up in human gene therapy].

PubMed

Portin, Petter

2016-01-01

Gene therapy is divided into somatic and germ line therapy. The latter involves reproductive cells or their stem cells, and its results are heritable. The effects of somatic gene therapy are generally restricted to a single tissue of the patient in question. Until now, all gene therapies in the world have belonged to the regime of somatic therapy, germ line therapy having been a theoretical possibility only. Very recently, however, a method has been developed which is applicable to germ line therapy as well. In addition to technical challenges, severe ethical problems are associated with germ line therapy, demanding opinion statement.

Radiation Therapy (For Parents)

MedlinePlus

... temporary, it can be permanent. Sore Mouth and Tooth Decay The tissues of the mouth may be sore ... and there may be an increased risk of tooth decay if a child received radiation therapy to the ...

Gene Therapy in the Cornea: 2005-present

PubMed Central

Mohan, Rajiv R.; Tovey, Jonathan C.K.; Sharma, Ajay; Tandon, Ashish

2011-01-01

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat corneal abnormalities have begun to surface. Identification of next generation viral and nanoparticle vectors, characterization of delivered gene levels, localization, and duration in the cornea, and significant success in controlling corneal disorders, particularly fibrosis and angiogenesis, in experimental animal disease models, with no major side effects have propelled gene therapy a step closer towards establishing gene-based therapies for corneal blindness. Recently, researchers have assessed the delivery of therapeutic genes for corneal diseases and disorders due to trauma, infections, chemical, mechanical, and surgical injury, and/or abnormal wound healing. This review provides an update on the developments in gene therapy for corneal diseases and discusses the barriers that hinder its utilization for delivering genes in the cornea. PMID:21967960

MCNP simulation of the dose distribution in liver cancer treatment for BNC therapy

NASA Astrophysics Data System (ADS)

Krstic, Dragana; Jovanovic, Zoran; Markovic, Vladimir; Nikezic, Dragoslav; Urosevic, Vlade

2014-10-01

The Boron Neutron Capture Therapy ( BNCT) is based on selective uptake of boron in tumour tissue compared to the surrounding normal tissue. Infusion of compounds with boron is followed by irradiation with neutrons. Neutron capture on 10B, which gives rise to an alpha particle and recoiled 7Li ion, enables the therapeutic dose to be delivered to tumour tissue while healthy tissue can be spared. Here, therapeutic abilities of BNCT were studied for possible treatment of liver cancer using thermal and epithermal neutron beam. For neutron transport MCNP software was used and doses in organs of interest in ORNL phantom were evaluated. Phantom organs were filled with voxels in order to obtain depth-dose distributions in them. The result suggests that BNCT using an epithermal neutron beam could be applied for liver cancer treatment.

Enhanced Intracellular Delivery and Tissue Retention of Nanoparticles by Mussel-Inspired Surface Chemistry.

PubMed

Chen, Kai; Xu, Xiaoqiu; Guo, Jiawei; Zhang, Xuelin; Han, Songling; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

2015-11-09

Nanomaterials have been broadly studied for intracellular delivery of diverse compounds for diagnosis or therapy. Currently it remains challenging for discovering new biomolecules that can prominently enhance cellular internalization and tissue retention of nanoparticles (NPs). Herein we report for the first time that a mussel-inspired engineering approach may notably promote cellular uptake and tissue retention of NPs. In this strategy, the catechol moiety is covalently anchored onto biodegradable NPs. Thus, fabricated NPs can be more effectively internalized by sensitive and multidrug resistant tumor cells, as well as some normal cells, resulting in remarkably potentiated in vitro activity when an antitumor drug is packaged. Moreover, the newly engineered NPs afford increased tissue retention post local or oral delivery. This biomimetic approach is promising for creating functional nanomaterials for drug delivery, vaccination, and cell therapy.

Random laser in biological tissues impregnated with a fluorescent anticancer drug

NASA Astrophysics Data System (ADS)

Lahoz, F.; Martín, I. R.; Urgellés, M.; Marrero-Alonso, J.; Marín, R.; Saavedra, C. J.; Boto, A.; Díaz, M.

2015-04-01

We have demonstrated that chemically modified anticancer drugs can provide random laser (RL) when infiltrated in a biological tissue. A fluorescent biomarker has been covalently bound to tamoxifen, which is one of the most frequently used drugs for breast cancer therapy. The light emitted by the drug-dye composite is scattered in tissue, which acts as a gain medium. Both non-coherent and coherent RL regimes have been observed. Moreover, the analysis of power Fourier transforms of coherent RL spectra indicates that the tissues show a dominant random laser cavity length of about 18 µm, similar to the average size of single cells. These results show that RL could be obtained from other drugs, if properly marked with a fluorescent tag, which could be appealing for new forms of combined opto-chemical therapies.

Multi-spectral fiber spectroscopy in 0,4-16μm range for biomedical applications(Conference Presentation)

NASA Astrophysics Data System (ADS)

Artyushenko, Viacheslav

2017-02-01

Various biomedical applications of fiber optics in a broad spectral range 0,4-16μm span from endoscopic imaging and Photo Dynamic Diagnostics (PDD) to laser power delivery for minimal invasive laser surgery, tissue coagulation and welding, Photo Dynamic Therapy (PDT), etc. Present review will highlight the latest results in advanced fiber solutions for a precise tissue diagnostics and control of some therapy methods - for so called "theranostic". Spectral fiber sensing for label free analysis of tissue composition helps to differentiate malignant and normal tissue to secure minimal invasive, but complete tumor removal or treatment. All key methods of Raman, fluorescence, diffuse reflection & MIR-absorption spectroscopy will be compared when used for the same spot of tissue - to select the most specific, sensitive and accurate method or to combine them for the synergy enhanced effect. The most informative spectral features for distinct organs/ tumor can be used to design special fiber sensors to be developed for portable and low cost applications with modern IT-features. Examples of multi-spectral tissue diagnostics promising for the future clinical applications will be presented to enable reduced mortality from cancer in the future. Translation of described methods into clinical practice will be discussed in comparison with the other method of optical diagnostics which should enhance modern medicine by less invasive, more precise and more effective methods of therapy to be fused with in-vivo diagnostics sensors & systems.

Role of adipose-derived stem cells in wound healing.

PubMed

Hassan, Waqar Ul; Greiser, Udo; Wang, Wenxin

2014-01-01

Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration. © 2014 by the Wound Healing Society.

Laser therapy for periodontitis

NASA Astrophysics Data System (ADS)

Efanov, O. I.

2001-04-01

An investigation was made of applying pulsed (lambda) equals 0.89 micrometers laser radiation in the treatment for early diagnosed periodontitis. The investigation was made on 65 patients (47 patients constituted the experimental group and 18 patients constituted a control group) affected by periodontitis. Clinical and functional tests revealed that laser therapy produced a string effect on the course of the illness. It reduced bleeding, inflammation, and pruritus. However, it did not produce an affect on electroexcitation. Biomicroscopic examinations and periodontium rheography revealed that the gingival blood flow became normal after the course of laser therapy. The capillary permeability and venous congestion decreased, which was confirmed by the increased time of vacuum tests, raised gingival temperature, reduced tissue clearance, and increased oxygen tension. Apart from that, laser therapy subsided fibrinolysis, proteolytic tissue activity, and decreased the exudative inflammation of periodontium.

Thrombolytic Therapy by Tissue Plasminogen Activator for Pulmonary Embolism.

PubMed

Islam, Md Shahidul

2017-01-01

Clinicians need to make decisions about the use of thrombolytic (fibrinolytic) therapy for pulmonary embolism (PE) after carefully considering the risks of major complications from bleeding, and the benefits of treatment, for each individual patient. They should probably not use systemic thrombolysis for PE patients with normal blood pressure. Treatment by human recombinant tissue plasminogen activator (rt-PA), alteplase, saves the lives of high-risk PE patients, that is, those with hypotension or in shock. Even in the absence of strong evidence, clinicians need to choose the most appropriate regimen for administering alteplase for individual patients, based on assessment of the urgency of the situation, risks for major complications from bleeding, and patient's body weight. In addition, invasive strategies should be considered when absolute contraindications for thrombolytic therapy exist, serious complications arise, or thrombolytic therapy fails.

[Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis].

PubMed

Su, Fei; Zheng, Ke; Fu, Yiyun; Wu, Qian; Tang, Yuan; Wang, Weiya; Jiang, Lili

2018-05-20

Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blum, R.H.; Greenberger, J.S.; Wilson, R.E.

1979-08-01

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M/sup 2/ day 1, Adriamycin (ADR) 60 mg/M/sup 2/ day 2, and DTIC 400 mg/M/sup 2/ days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M/sup 2/. Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks,more » and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment.« less

Gastro-intestinal autoimmunity: preclinical experiences and successful therapy of fistulizing bowel diseases and gut Graft versus host disease by mesenchymal stromal cells.

PubMed

Voswinkel, Jan; Francois, Sabine; Gorin, Norbert-Claude; Chapel, Alain

2013-07-01

Mesenchymal stromal cells (MSC) are multipotent adult stem cells with the potential to regenerate tissue damage and inhibit inflammation and fibrosis in parallel. As they are non-immunogenic, MSC can be safely auto- and allotransplanted and consequently represent a therapeutic option for refractory connective tissue diseases and fistulizing colitis like Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, 22 are on autoimmune diseases and 27 are actually recruiting bowel disease' patients. More than 1,500 patients with bowel diseases like Crohn's disease were treated in clinical trials by local as well as systemic MSC therapy. Phase I and II trials on fistula documented the feasibility and safety of MSC therapy, and a significant superiority compared to fibrin glue in fistulizing bowel diseases was demonstrated. Autologous as well as allogeneic use of Bone marrow as well as of adipose tissue-derived MSC are feasible. In refractory Graft versus host disease, especially in refractory gut Graft versus host diseases, encouraging results were reported using MSC. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets toward an increase in T regulatory cells and a decrease in activated effector T cells. Mesenchymal stem cells represent a safe therapy for patients with refractory inflammatory bowel diseases.

Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells.

PubMed

Ager, Ann; Watson, H Angharad; Wehenkel, Sophie C; Mohammed, Rebar N

2016-04-15

The success of adoptive T-cell therapies for the treatment of cancer patients depends on transferred T-lymphocytes finding and infiltrating cancerous tissues. For intravenously transferred T-cells, this means leaving the bloodstream (extravasation) from tumour blood vessels. In inflamed tissues, a key event in extravasation is the capture, rolling and arrest of T-cells inside blood vessels which precedes transmigration across the vessel wall and entry into tissues. This depends on co-ordinated signalling of selectins, integrins and chemokine receptors on T-cells by their respective ligands which are up-regulated on inflamed blood vessels. Clinical data and experimental studies in mice suggest that tumour blood vessels are anergic to inflammatory stimuli and the recruitment of cytotoxic CD8(+)T-lymphocytes is not very efficient. Interestingly, and somewhat counter-intuitively, anti-angiogenic therapy can promote CD8(+)T-cell infiltration of tumours and increase the efficacy of adoptive CD8(+)T-cell therapy. Rather than inhibit tumour angiogenesis, anti-angiogenic therapy 'normalizes' (matures) tumour blood vessels by promoting pericyte recruitment, increasing tumour blood vessel perfusion and sensitizing tumour blood vessels to inflammatory stimuli. A number of different approaches are currently being explored to increase recruitment by manipulating the expression of homing-associated molecules on T-cells and tumour blood vessels. Future studies should address whether these approaches improve the efficacy of adoptive T-cell therapies for solid, vascularized cancers in patients. © 2016 Authors; published by Portland Press Limited.

Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells

PubMed Central

Ager, Ann; Watson, H. Angharad; Wehenkel, Sophie C.; Mohammed, Rebar N.

2016-01-01

The success of adoptive T-cell therapies for the treatment of cancer patients depends on transferred T-lymphocytes finding and infiltrating cancerous tissues. For intravenously transferred T-cells, this means leaving the bloodstream (extravasation) from tumour blood vessels. In inflamed tissues, a key event in extravasation is the capture, rolling and arrest of T-cells inside blood vessels which precedes transmigration across the vessel wall and entry into tissues. This depends on co-ordinated signalling of selectins, integrins and chemokine receptors on T-cells by their respective ligands which are up-regulated on inflamed blood vessels. Clinical data and experimental studies in mice suggest that tumour blood vessels are anergic to inflammatory stimuli and the recruitment of cytotoxic CD8+ T-lymphocytes is not very efficient. Interestingly, and somewhat counter-intuitively, anti-angiogenic therapy can promote CD8+ T-cell infiltration of tumours and increase the efficacy of adoptive CD8+ T-cell therapy. Rather than inhibit tumour angiogenesis, anti-angiogenic therapy ‘normalizes’ (matures) tumour blood vessels by promoting pericyte recruitment, increasing tumour blood vessel perfusion and sensitizing tumour blood vessels to inflammatory stimuli. A number of different approaches are currently being explored to increase recruitment by manipulating the expression of homing-associated molecules on T-cells and tumour blood vessels. Future studies should address whether these approaches improve the efficacy of adoptive T-cell therapies for solid, vascularized cancers in patients. PMID:27068943

Postoperative Therapy for Chronic Thumb Carpometacarpal (CMC) Joint Dislocation.

PubMed

Wollstein, Ronit; Michael, Dafna; Harel, Hani

2016-01-01

Surgical arthroplasty of thumb carpometacarpal (CMC) joint osteoarthritis is commonly performed. Postoperative therapeutic protocols aim to improve range of motion and function of the revised thumb. We describe a case in which the thumb CMC joint had been chronically dislocated before surgery, with shortening of the soft-tissue dynamic and static stabilizers of the joint. The postoperative protocol addressed the soft tissues using splinting and exercises aimed at lengthening and strengthening these structures, with good results. It may be beneficial to evaluate soft-tissue tension and the pattern of thumb use after surgery for thumb CMC joint osteoarthritis to improve postoperative functional results. Copyright © 2016 by the American Occupational Therapy Association, Inc.

[The role of neurotrophic factors in regeneration of the nervous system].

PubMed

Machaliński, Bogusław; Lażewski-Banaszak, Piotr; Dąbkowska, Elżbieta; Paczkowska, Edyta; Gołąb-Janowska, Monika; Nowacki, Przemysław

2012-01-01

Neurotrophic factors regulate survival, development, and function of nervous tissue. They act via two different classes of receptors and activation of various signaling pathways in the target cells. Illumination of their physiological role in the maintenance of central nervous system homeostasis as well as regeneration of damaged tissue have ignited expectations to heal neurodegenerative diseases, including amyotrophic late-ral sclerosis and Parkinson disease. Advances in pharmaco-therapy, gene therapy, and stem cell biology have enabled development of novel therapies with application of regenerating cell transplantation. In the foreseeable future, it may lead to the establishment of safe and effective ways of treatment of these severe and currently incurable diseases.

Salivary enhancement: current status and future therapies.

PubMed

Atkinson, J C; Baum, B J

2001-10-01

Saliva provides the principal protective milieu for teeth by modulating oral microbial ecosystems and reversing the initial phases of caries development. Patients with inadequate salivary function are at increased risk for dental decay. Therefore, it is likely that therapies that increase overall fluid output of these individuals will reverse early carious lesions. The most common causes of salivary dysfunction are medication usage, Sjögren's syndrome, and damage of salivary parenchyma during therapeutic irradiation. For patients with remaining functional acinar tissue, treatment with the parasypathomimetic secretogogues pilocarpine and Cevimeline may provide relief. However, these medications do not benefit all patients. The possibilities of using gene therapy and tissue engineering to develop treatments for those with severe salivary dysfunction are discussed.

Laser therapy in the management of dental and oro-facial trauma

NASA Astrophysics Data System (ADS)

Darbar, Arun A.

2007-02-01

This is a clinical presentation demonstrating the efficacy of laser therapy in the treatment of patients presenting with trauma to both the hard and soft tissue in the orofacial region. The use of laser therapy aids the management of these cases where the patients often present with anxiety and a low pain threshold. The outcomes in these cases indicate good patient acceptance of the treatment, enhanced repair and tissue response suggesting that this form of treatment can be indicated for these patients. A combination of hard and soft lasers are used for the comprehensive dental management and treatment of these cases. The lasers used are a 810nm diode and an Er.CrYSGG.

Potential roles for uncoupling proteins in HIV lipodystrophy.

PubMed

Nolan, David; Pace, Craig

2004-07-01

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

Periodontics--tissue engineering and the future.

PubMed

Douglass, Gordon L

2005-03-01

Periodontics has a long history of utilizing advances in science to expand and improve periodontal therapies. Recently the American Academy of Periodontology published the findings of the Contemporary Science Workshop, which conducted state-of-the-art evidence-based reviews of current and emerging areas in periodontics. The findings of this workshop provide the basis for an evidence-based approach to periodontal therapy. While the workshop evaluated all areas of periodontics, it is in the area of tissue engineering that the most exciting advances are becoming a reality.

Acceleration Of Wound Healing Ny Photodynamic Therapy

DOEpatents

Hasan, Tayyaba; Hamblin, Michael R.; Trauner, Kenneth

2000-08-22

Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

Future role of endoscopic ultrasound in personalized management of pancreatic cancer

PubMed Central

Ooi, Marie; Phan, An; Nguyen, Nam Q.

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) is aggressive and lethal with the majority of cases presenting with advanced unresectable disease due to delayed diagnosis. Despite improvement in surgery, chemotherapies, and intensive care medicine, the outcome of PDAC remains poor, which may relate to the tumor biology. Recent data suggest that PDAC is a “systemic cancer” with complex molecular or genomics derangement with marked heterogeneity. The ability to characterize the PDAC better by detailed evaluation of tissue biomarkers or genomics allows for improved prediction of prognosis and stratification of treatment, a concept known as “personalized cancer therapy.” Using tissue from resected PDAC specimens has several weaknesses and is only possible in 20% of patients with PDAC. Endoscopic ultrasound (EUS)-guided biopsy overcomes these weaknesses, and with recent advancements in needle technology, tissue can be obtained for personalized cancer therapy for all patients with PDAC. This review aims to outline our current understanding of the molecular biology of PDAC specifically focusing on how EUS-guided biopsy may play a fundamental role in tissue acquisition, allowing for assessment and stratify therapy according to the individual cancer biology as we move toward the era of precision medicine. PMID:29063873

Ultralow-Power Near Infrared Lamp Light Operable Targeted Organic Nanoparticle Photodynamic Therapy.

PubMed

Huang, Ling; Li, Zhanjun; Zhao, Yang; Zhang, Yuanwei; Wu, Shuang; Zhao, Jianzhang; Han, Gang

2016-11-09

Tissue penetration depth is a major challenge in practical photodynamic therapy (PDT). A biocompatible and highly effective near infrared (NIR)-light-absorbing carbazole-substituted BODIPY (Car-BDP) molecule is reported as a class of imaging-guidable deep-tissue activatable photosensitizers for PDT. Car-BDP possesses an intense, broad NIR absorption band (600-800 nm) with a remarkably high singlet oxygen quantum yield (Φ Δ = 67%). After being encapsulated with biodegradable PLA-PEG-FA polymers, Car-BDP can form uniform and small organic nanoparticles that are water-soluble and tumor-targetable. Rather than using laser light, such nanoparticles offer an unprecedented deep-tissue, tumor targeting photodynamic therapeutic effect by using an exceptionally low-power-density and cost-effective lamp light (12 mW cm -2 ). In addition, these nanoparticles can be simultaneously traced in vivo due to their excellent NIR fluorescence. This study signals a major step forward in photodynamic therapy by developing a new class of NIR-absorbing biocompatible organic nanoparticles for effective targeting and treatment of deep-tissue tumors. This work also provides a potential new platform for precise tumor-targeting theranostics and novel opportunities for future affordable clinical cancer treatment.

Distally based saphenous neurocutaneous perforator flap combined with vac therapy for soft tissue reconstruction and hardware salvage in the lower extremities.

PubMed

Wen, Gen; Wang, Chun-Yang; Chai, Yi-Min; Cheng, Liang; Chen, Ming; Yi-Min, L V

2013-11-01

The complex wound with the exposed hardware and infection is one of the common complications after the internal fixation of the tibia fracture. The salvage of hardware and reconstruction of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to cover the complex wound with exposed hardware in the lower extremities. © 2013 Wiley Periodicals, Inc.

Ultrasound Imaging in Radiation Therapy: From Interfractional to Intrafractional Guidance

PubMed Central

Western, Craig; Hristov, Dimitre

2015-01-01

External beam radiation therapy (EBRT) is included in the treatment regimen of the majority of cancer patients. With the proliferation of hypofractionated radiotherapy treatment regimens, such as stereotactic body radiation therapy (SBRT), interfractional and intrafractional imaging technologies are becoming increasingly critical to ensure safe and effective treatment delivery. Ultrasound (US)-based image guidance systems offer real-time, markerless, volumetric imaging with excellent soft tissue contrast, overcoming the limitations of traditional X-ray or computed tomography (CT)-based guidance for abdominal and pelvic cancer sites, such as the liver and prostate. Interfractional US guidance systems have been commercially adopted for patient positioning but suffer from systematic positioning errors induced by probe pressure. More recently, several research groups have introduced concepts for intrafractional US guidance systems leveraging robotic probe placement technology and real-time soft tissue tracking software. This paper reviews various commercial and research-level US guidance systems used in radiation therapy, with an emphasis on hardware and software technologies that enable the deployment of US imaging within the radiotherapy environment and workflow. Previously unpublished material on tissue tracking systems and robotic probe manipulators under development by our group is also included. PMID:26180704

Successful Nonsurgical Management of Periapical Lesions of Endodontic Origin: A Conservative Orthograde Approach

PubMed Central

Karunakaran, J. V.; Abraham, Chris Susan; Karthik, A. Kaneesh; Jayaprakash, N.

2017-01-01

Periapical lesions of endodontic origin are common pathological conditions affecting periradicular tissues. Microbial infection of pulpal tissues is primarily responsible for initiation and progression of apical periodontitis. The primary objective of endodontic therapy should be to restore involved teeth to a state of normalcy nonsurgically. Different nonsurgical management techniques, namely, conservative root canal therapy, decompression technique, method using calcium hydroxide, aspiration-irrigation technique, lesion sterilization and tissue repair therapy, active nonsurgical decompression technique, and the apexum procedure have been advocated. New techniques which use drug-loaded injectable scaffolds, simvastatin, and epigallocatechin-3-gallate have been tried. Surgical option should be considered when intra- or extra-radicular infections are persistent. Incidence of nonendodontic periapical lesions has also been reported. An accurate diagnosis of the periapical lesion whether it is of endodontic or nonendodontic origin has to be made. Surgical methods have many disadvantages, and hence should be considered as an option only in the case of failure of nonsurgical techniques. Assessment of healing of periapical lesions has to be done periodically which necessitates a long-term follow-up. Even large periapical lesions and retreatment cases where the lesion is of endodontic origin have been successfully managed nonsurgically with orthograde endodontic therapy. PMID:29284973

Autologous transplantation of cryopreserved ovarian tissue to induce puberty-the endocrinologists' view.

PubMed

von Wolff, Michael; Stute, Petra; Flück, Christa

2016-12-01

Transplantation of cryopreserved ovarian tissue has been shown to successfully induce pregnancies. Furthermore, puberty may be induced by transplanted ovarian tissue in girls suffering from premature primary ovarian insufficiency (PPOI) due to gonadotoxic therapy. Therefore, the question arises if ovarian tissue cryopreservation should be recommended for puberty induction in prepubertal girls with cancer prior to gonadotoxic therapies. Although this strategy seems to be more natural than administering exogenous steroid sex hormones, there are some disadvantages from the endocrinological point of view. During physiologic puberty, serum estradiol levels increase very slowly, followed by irregular and finally regular ovulations with progesterone production during the luteal phase. PPOI presents as hypergonadotrophic hypogonadism. When transplanting ovarian tissue in girls with PPOI, the elevated gonadotrophins will promote a sudden follicular growth of one or several follicles with a sharp increase of serum estrogen levels and regular ovulations. This will result into an accelerated pubertal development with the risk of overt weight gain, cutaneous striae and premature growth stop possibly leading to psychological implications. Transplantation of cryopreserved ovarian tissue should not be recommended as an alternative to medically induced puberty.

HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy.

PubMed

Honeycutt, Jenna B; Thayer, William O; Baker, Caroline E; Ribeiro, Ruy M; Lada, Steven M; Cao, Youfang; Cleary, Rachel A; Hudgens, Michael G; Richman, Douglas D; Garcia, J Victor

2017-05-01

Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (∼33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.

Thermal injury models for optical treatment of biological tissues: a comparative study.

PubMed

Fanjul-Velez, Felix; Ortega-Quijano, Noe; Salas-Garcia, Irene; Arce-Diego, Jose L

2010-01-01

The interaction of optical radiation with biological tissues causes an increase in the temperature that, depending on its magnitude, can provoke a thermal injury process in the tissue. The establishment of laser irradiation pathological limits constitutes an essential task, as long as it enables to fix and delimit a range of parameters that ensure a safe treatment in laser therapies. These limits can be appropriately described by kinetic models of the damage processes. In this work, we present and compare several models for the study of thermal injury in biological tissues under optical illumination, particularly the Arrhenius thermal damage model and the thermal dosimetry model based on CEM (Cumulative Equivalent Minutes) 43°C. The basic concepts that link the temperature and exposition time with the tissue injury or cellular death are presented, and it will be shown that they enable to establish predictive models for the thermal damage in laser therapies. The results obtained by both models will be compared and discussed, highlighting the main advantages of each one and proposing the most adequate one for optical treatment of biological tissues.

Tissue engineering for lateral ridge augmentation with recombinant human bone morphogenetic protein 2 combination therapy: a case report.

PubMed

Mandelaris, George A; Spagnoli, Daniel B; Rosenfeld, Alan L; McKee, James; Lu, Mei

2015-01-01

This case report describes a tissue-engineered reconstruction with recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ ACS) + cancellous allograft and space maintenance via Medpor Contain mesh in the treatment of a patient requiring maxillary and mandibular horizontal ridge augmentation to enable implant placement. The patient underwent a previously unsuccessful corticocancellous bone graft at these sites. Multiple and contiguous sites in the maxilla and in the mandibular anterior, demonstrating advanced lateral ridge deficiencies, were managed using a tissue engineering approach as an alternative to autogenous bone harvesting. Four maxillary and three mandibular implants were placed 9 and 10 months, respectively, after tissue engineering reconstruction, and all were functioning successfully after 24 months of follow-up. Histomorphometric analysis of a bone core obtained at the time of the maxillary implant placement demonstrated a mean of 76.1% new vital bone formation, 22.2% marrow/cells, and 1.7% residual graft tissue. Tissue engineering for lateral ridge augmentation with combination therapy requires further research to determine predictability and limitations.

Emerging biomarkers in breast cancer care.

PubMed

Napieralski, Rudolf; Brünner, Nils; Mengele, Karin; Schmitt, Manfred

2010-08-01

Currently, decision-making for breast cancer treatment in the clinical setting is mainly based on clinical data, histomorphological features of the tumor tissue and a few cancer biomarkers such as steroid hormone receptor status (estrogen and progesterone receptors) and oncoprotein HER2 status. Although various therapeutic options were introduced into the clinic in recent decades, with the objective of improving surgery, radiotherapy, biochemotherapy and chemotherapy, varying response of individual patients to certain types of therapy and therapy resistance is still a challenge in breast cancer care. Therefore, since breast cancer treatment should be based on individual features of the patient and her tumor, tailored therapy should be an option by integrating cancer biomarkers to define patients at risk and to reliably predict their course of the disease and/or response to cancer therapy. Recently, candidate-marker approaches and genome-wide transcriptomic and epigenetic screening of different breast cancer tissues and bodily fluids resulted in new promising biomarker panels, allowing breast cancer prognosis, prediction of therapy response and monitoring of therapy efficacy. These biomarkers are now subject of validation in prospective clinical trials.

76 FR 13404 - Cancer Therapy Evaluation Program Intellectual Property Option to Collaborator

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... with the Agent (including specimens obtained from NCI CTEP-funded tissue banks) (``Section B Inventions... tissue banks) (``Section B Inventions''): Institution agrees to grant to Collaborator(s): (i) a paid-up...

Facts about the Cornea and Corneal Disease

MedlinePlus

... can be used as a laboratory model to test potential therapies, or used as therapies on their own to promote regrowth of healthy corneal tissue. For example, one group of researchers is developing a source ...

Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

PubMed

Harris, M; Patenaude, P; Cooperberg, P; Filipenko, D; Thorne, A; Raboud, J; Rae, S; Dailey, P; Chernoff, D; Todd, J; Conway, B; Montaner, J S

1997-11-01

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies

PubMed Central

Kirkton, Robert D.; Bursac, Nenad

2012-01-01

Patch-clamp recordings in single-cell expression systems have been traditionally used to study the function of ion channels. However, this experimental setting does not enable assessment of tissue-level function such as action potential (AP) conduction. Here we introduce a biosynthetic system that permits studies of both channel activity in single cells and electrical conduction in multicellular networks. We convert unexcitable somatic cells into an autonomous source of electrically excitable and conducting cells by stably expressing only three membrane channels. The specific roles that these expressed channels have on AP shape and conduction are revealed by different pharmacological and pacing protocols. Furthermore, we demonstrate that biosynthetic excitable cells and tissues can repair large conduction defects within primary 2- and 3-dimensional cardiac cell cultures. This approach enables novel studies of ion channel function in a reproducible tissue-level setting and may stimulate the development of new cell-based therapies for excitable tissue repair. PMID:21556054

New Technique of Applying Topical Oxygen Therapy as a Cost-Effective Procedure.

PubMed

Agarwal, Vivek; Aroor, Shashank; Gupta, Nikhil; Gupta, Arun; Agarwal, Nitin; Kaur, Navneet

2015-12-01

To describe the newly designed technique of applying topical oxygen therapy for large wounds. C arm sterile disposable cover is used for covering the wound. For abdominal and pelvis wounds, two artificial holes are created at one end of the cover for the inclusion of the limb. Free end of the cover is secured with adhesive, and a hole is created for the insertion of the suction catheter. Oxygen cylinder is connected to the suction catheter, and oxygen is supplied at the rate of 10 L/min. Three patients were treated with topical oxygen therapy. These patients were cases of necrotizing soft tissue infections and large post traumatic wounds. There were less requirements of debridement and granulation tissue appeared earlier. The cost of one cycle of the therapy is less than 500 INR. Topical oxygen therapy is the recent modality for improved wound healing. The novel method of applying topical oxygen devised by us is effective, feasible, and cost-effective as compared to standard devices.

Evaluation of nitazoxanide for the treatment of disseminated cystic echinococcosis: report of five cases and literature review.

PubMed

Pérez-Molina, José A; Díaz-Menéndez, Marta; Gallego, José I; Norman, Francesca; Monge-Maillo, Begoña; Ayala, Ana Pérez; López-Vélez, Rogelio

2011-02-01

We aimed to evaluate the effectiveness of nitazoxanide in disseminated cystic echinococcosis (DCE) that failed to respond to surgical and antiparasitic therapy. We report on seven patients (five of them with bony involvement): two cases from the literature and five patients who were included in a compassionate trial of nitazoxanide therapy in our hospital. Median follow-up time until nitazoxanide therapy was 12 years and all patients had received prior medical treatment and extensive surgery. Nitazoxanide (500 mg/12 h) in combination with albendazole, with/without praziquantel, was administered for 3-24 months. Three patients improved: one with muscle involvement (clinico-radiological response), one with lung involvement (radiological response), and another with soft tissue and bony involvement (clinico-radiological response of soft tissue cysts). There was one discontinuation after 15 days of starting therapy. Nitazoxanide combination therapy could have a role in the treatment of DCE when there is no bony involvement. Long-term safety profile seems to be favorable.

Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

PubMed Central

Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

2015-01-01

Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced Photodynamic Therapy.

PubMed

Yao, Mengyu; Ma, Lun; Li, Lihua; Zhang, Junying; Lim, Rebecca; Chen, Wei; Zhang, Yu

2016-10-01

Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.

Identification of Reduced-Order Thermal Therapy Models Using Thermal MR Images: Theory and Validation

PubMed Central

2013-01-01

In this paper, we develop and validate a method to identify computationally efficient site- and patient-specific models of ultrasound thermal therapies from MR thermal images. The models of the specific absorption rate of the transduced energy and the temperature response of the therapy target are identified in the reduced basis of proper orthogonal decomposition of thermal images, acquired in response to a mild thermal test excitation. The method permits dynamic reidentification of the treatment models during the therapy by recursively utilizing newly acquired images. Such adaptation is particularly important during high-temperature therapies, which are known to substantially and rapidly change tissue properties and blood perfusion. The developed theory was validated for the case of focused ultrasound heating of a tissue phantom. The experimental and computational results indicate that the developed approach produces accurate low-dimensional treatment models despite temporal and spatial noises in MR images and slow image acquisition rate. PMID:22531754

Predicting Sensitivity of Breast Tumors to Src-targeted Therapies Through Assessment of Cas/Src/BCAR3 Activity

DTIC Science & Technology

2017-10-01

expression is elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and DCIS... compared to IDC. (2) BCAR3 is significantly upregulated in triple negative breast cancer and normal tissue; (3) BCAR3 expression shows a modest...expression was seen to be elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and

Influence of Spinal Manipulative Therapy Force Magnitude and Application Site on Spinal Tissue Loading: A Biomechanical Robotic Serial Dissection Study in Porcine Motion Segments.

PubMed

Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Greg

In order to define the relation between spinal manipulative therapy (SMT) input parameters and the distribution of load within spinal tissues, the aim of this study was to determine the influence of force magnitude and application site when SMT is applied to cadaveric spines. In 10 porcine cadavers, a servo-controlled linear actuator motor provided a standardized SMT simulation using 3 different force magnitudes (100N, 300N, and 500N) to 2 different cutaneous locations: L3/L4 facet joint (FJ), and L4 transverse processes (TVP). Vertebral kinematics were tracked optically using indwelling bone pins, the motion segment removed and mounted in a parallel robot equipped with a 6-axis load cell. The kinematics of each SMT application were replicated robotically. Serial dissection of spinal structures was conducted to quantify loading characteristics of discrete spinal tissues. Forces experienced by the L3/L4 segment and spinal structures during SMT replication were recorded and analyzed. Spinal manipulative therapy force magnitude and application site parameters influenced spinal tissues loading. A significant main effect (P < .05) of force magnitude was observed on the loads experienced by the intact specimen and supra- and interspinous ligaments. The main effect of application site was also significant (P < .05), influencing the loading of the intact specimen and facet joints, capsules, and ligamentum flavum (P < .05). Spinal manipulative therapy input parameters of force magnitude and application site significantly influence the distribution of forces within spinal tissues. By controlling these SMT parameters, clinical outcomes may potentially be manipulated. Copyright © 2017. Published by Elsevier Inc.

Experimental investigations of an endoluminal ultrasound applicator for MR-guided thermal therapy of pancreatic cancer

NASA Astrophysics Data System (ADS)

Adams, Matthew; Salgaonkar, Vasant; Jones, Peter; Plata, Juan; Chen, Henry; Pauly, Kim Butts; Sommer, Graham; Diederich, Chris

2017-03-01

An MR-guided endoluminal ultrasound applicator has been proposed for palliative and potential curative thermal therapy of pancreatic tumors. Minimally invasive ablation or hyperthermia treatment of pancreatic tumor tissue would be performed with the applicator positioned in the gastrointestinal (GI) lumen, and sparing of the luminal tissue would be achieved with a water-cooled balloon surrounding the ultrasound transducers. This approach offers the capability of conformal volumetric therapy for fast treatment times, with control over the 3D spatial deposition of energy. Prototype endoluminal ultrasound applicators have been fabricated using 3D printed fixtures that seat two 3.2 or 5.6 MHz planar or curvilinear transducers and contain channels for wiring and water flow. Spiral surface coils have been integrated onto the applicator body to allow for device localization and tracking for therapies performed under MR guidance. Heating experiments with a tissue-mimicking phantom in a 3T MR scanner were performed and demonstrated capability of the prototype to perform volumetric heating through duodenal luminal tissue under real-time PRF-based MR temperature imaging (MRTI). Additional experiments were performed in ex vivo pig carcasses with the applicator inserted into the esophagus and aimed towards liver or soft tissue surrounding the spine under MR guidance. These experiments verified the capacity of heating targets up to 20-25 mm from the GI tract. Active device tracking and automated prescription of imaging and temperature monitoring planes through the applicator were made possible by using Hadamard encoded tracking sequences to obtain the coordinates of the applicator tracking coils. The prototype applicators have been integrated with an MR software suite that performs real-time device tracking and temperature monitoring.

Sustained secretion of anti-tumor necrosis factor α monoclonal antibody from ex vivo genetically engineered dermal tissue demonstrates therapeutic activity in mouse model of rheumatoid arthritis.

PubMed

Zafir-Lavie, Inbal; Miari, Reem; Sherbo, Shay; Krispel, Simi; Tal, Osnat; Liran, Atar; Shatil, Tamar; Badinter, Felix; Goltsman, Haim; Shapir, Nir; Benhar, Itai; Neil, Garry A; Panet, Amos

2017-08-01

Rheumatoid arthritis (RA) is a symmetric inflammatory polyarthritis associated with high concentrations of pro-inflammatory, cytokines including tumor necrosis factor (TNF)-α. Adalimumab is a monoclonal antibody (mAb) that binds TNF-α, and is widely used to treat RA. Despite its proven clinical efficacy, adalimumab and other therapeutic mAbs have disadvantages, including the requirement for repeated bolus injections and the appearance of treatment limiting anti-drug antibodies. To address these issues, we have developed an innovative ex vivo gene therapy approach, termed transduced autologous restorative gene therapy (TARGT), to produce and secrete adalimumab for the treatment of RA. Helper-dependent (HD) adenovirus vector containing adalimumab light and heavy chain coding sequences was used to transduce microdermal tissues and cells of human and mouse origin ex vivo, rendering sustained secretion of active adalimumab. The genetically engineered tissues were subsequently implanted in a mouse model of RA. Transduced human microdermal tissues implanted in SCID mice demonstrated 49 days of secretion of active adalimumab in the blood, at levels of tens of microgram per milliliter. In addition, transduced autologous dermal cells were implanted in the RA mouse model and demonstrated statistically significant amelioration in RA symptoms compared to naïve cell implantation and were similar to recombinant adalimumab bolus injections. The results of the present study report microdermal tissues engineered to secrete active adalimumab as a proof of concept for sustained secretion of antibody from the novel ex vivo gene therapy TARGT platform. This technology may now be applied to a range of antibodies for the therapy of other diseases. Copyright © 2017 John Wiley & Sons, Ltd.

Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

PubMed Central

Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, Ramasamy; Mao, Hai-Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

2009-01-01

Background Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). Methods and Findings Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. Conclusion Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID:19809493

Alpha-fetoprotein, stem cells and cancer: how study of the production of alpha-fetoprotein during chemical hepatocarcinogenesis led to reaffirmation of the stem cell theory of cancer.

PubMed

Sell, Stewart

2008-01-01

Identification of the cells in the liver that produce alpha-fetoprotein during development, in response to liver injury and during the early stages of chemical hepatocarcinogenesis led to the conclusion that maturation arrest of liver-determined tissue stem cells was the cellular process that gives rise to hepatocellular carcinomas. When the cellular changes in these processes were compared to that of the formation of teratocarcinomas, the hypothesis arose that all cancers arise from maturation arrest of tissue-determined stem cells. This was essentially a reinterpretation of the embryonal rest theory of cancer whereby tissue stem cells take the role of embryonal rests. A corollary of the stem cell theory of the origin of cancer is that cancers contain the same functional cell populations as normal tissues: stem cells, transit-amplifying cells and mature cells. Cancer stem cells retain the essential feature of normal stem cells: the ability to self-renew. Growth of cancers is due to continued proliferation of cancer transit-amplifying cells that do not differentiate to mature cells (maturation arrest). On the other hand, cancer stem cells generally divide very rarely and contribute little to tumor growth. However, the presence of cancer stem cells in tumors is believed to be responsible for the properties of immortalization, transplantability and resistance to therapy characteristic of cancers. Current therapies for cancer (chemotherapy, radiotherapy, antiangiogenesis and differentiation therapy) are directed against the cancer transit-amplifying cells. When these therapies are discontinued, the cancer reforms from the cancer stem cells. Therapy directed toward interruption of the cell signaling pathways that maintain cancer stem cells could lead to new modalities to the prevention of regrowth of the cancer. Copyright 2008 S. Karger AG, Basel.

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review.

PubMed

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan; Subbiah, Suresh Kumar

2018-02-13

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

ALPHA-FETOPROTEIN (AFP), STEM CELLS, AND CANCER: HOW STUDY OF THE PRODUCTION OF AFP DURING CHEMICAL HEPATOCARCINOGENESIS LED TO REAFFIRMATION OF THE STEM CELL THEORY OF CANCER

PubMed Central

Sell, Stewart

2008-01-01

Identification of the cells in the liver that produce alpha-fetoprotein (AFP) during development, in response to liver injury, and during the early stages of chemical hepatocarcinogenesis led to the conclusion that maturation arrest of liver-determined tissue stem cells was the cellular process that gives rise to hepatocellular carcinomas (HCC). When the cellular changes in these processes were compared that of the formation of teratocarcinomas, the hypothesis arose that all cancers arise from maturation arrest of tissue determined stem cells. This was essentially a reinterpretation of the embryonal rest theory of cancer whereby tissue stem cells take the role of embryonal rests. A corollary of the stem cell theory of the origin of cancer is that cancers contain the same functional cell populations as do normal tissues: stem cells, transit-amplifying cells, and mature cells. Cancer stem cells retain the essential feature of normal stem cells: the ability to self-renew. Growth of cancers is due to continued proliferation of cancer transit-amplifying cells that do not differentiate to mature cells (maturation arrest). On the other hand, cancer stem cells generally divide very rarely and contribute little to tumor growth. However, the presence of cancer stem cells in tumors is believed to be responsible for the properties of immortalization, transplantability and resistance to therapy characteristic of cancers. Current therapies for cancer (chemotherapy, radiotherapy, anti-angiogenesis and differentiation therapy) are directed against the cancer transit amplifying cells. When these therapies are discontinued, the cancer re-forms from the cancer stem cells. Therapy directed toward interruption of the cell-signaling pathways that maintain cancer stem cells could lead to new modalities to the prevention of re-growth of the cancer. PMID:18612221

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists.

PubMed

Sargos, P; Charleux, T; Haas, R L; Michot, A; Llacer, C; Moureau-Zabotto, L; Vogin, G; Le Péchoux, C; Verry, C; Ducassou, A; Delannes, M; Mervoyer, A; Wiazzane, N; Thariat, J; Sunyach, M P; Benchalal, M; Laredo, J D; Kind, M; Gillon, P; Kantor, G

2018-04-01

The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Myofascial treatment for patients with acetabular labral tears: a single-subject research design study.

PubMed

Cashman, Glenn E; Mortenson, W Ben; Gilbart, Michael K

2014-08-01

Single-subject research design using 4 consecutive patients. To assess whether treatment using soft tissue therapy (ART or Active Release Technique), stretching, and strengthening of the hip abductors, hip external rotators, and tensor fascia latae muscles reduces pain and improves self-reported hip function in patients with acetabular labral tears who also have posterolateral hip pain of suspected myofascial origin. Acetabular labral tears cause pain in some but not all patients. Pain commonly presents anteriorly but may also present posteriorly and laterally. The standard of care is arthroscopic repair, which helps many but not all patients. It is possible that these patients may present with extra-articular contributions to their pain, such as myofascial pain, making their clinical presentation more complex. No previous study has assessed soft tissue therapy as a treatment option for this subset of patients. This A-B-A design used repeated measures of the Hip Outcome Score and visual analog scale for pain. Four patients were treated for 6 to 8 weeks, using a combination of soft tissue therapy, stretching, and strengthening for the hip abductors, external rotators, and tensor fascia latae. Data were assessed visually, statistically, and by comparing mean differences before and after intervention. All 4 patients experienced both statistically significant and clinically meaningful improvement in posterolateral hip pain and hip-related function. Three patients also experienced reduction in anteromedial hip pain. Myofascial hip pain may contribute to hip-related symptoms and disability in patients with acetabular labral tears and posterolateral hip pain. These patients may benefit from soft tissue therapy combined with stretching and strengthening exercises targeting the hip abductors, tensor fascia latae, and hip external rotator muscles. Level of Evidence Therapy, level 4.

[Prognostic impact of Helicobacter pylori infection and eradication therapy in gastric mucosa-associated lymphoid tissue lymphoma].

PubMed

Park, Sang Hyuk; Chi, Hyun-Sook; Park, Seo-Jin; Jang, Seongsoo; Park, Chan-Jeoung; Huh, Joo Ryung

2010-12-01

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection and H. pylori eradication is used as its first-line therapy. However, controversies exist about the prognostic value of H. pylori infection in these patients. We evaluated the prognostic impact of H. pylori infection and eradication therapy in gastric MALT lymphoma. A total of 292 patients diagnosed with MALT lymphoma since 2000 were analysed. MALT lymphoma was diagnosed with tissue biopsy and H. pylori infection was diagnosed with hematoxylin-eosin and additional Warthin-Starry stains on tissue sections. Clinical variables such as bone marrow (BM) involvement, multiorgan involvement, tumor stage at diagnosis, and remission were obtained with retrospective review of electronic medical records. Non-gastric MALT lymphoma patients showed higher multiorgan involvement rates (26.6% vs. 9.6%, P<0.001) and higher proportion of stage ≥ 3 (27.7% vs. 16.7%, P=0.029) than gastric cases. Regarding gastric MALT lymphoma, patients with H. pylori infection at diagnosis showed significantly less BM (2.1% vs. 21.8%, P<0.001) and multiorgan involvement rates (6.3% vs. 18.2%, P=0.011) than those without infection. But there was no significant difference in remission rates between them. In contrast, those with successful H. pylori eradication therapy showed significantly higher remission rates (81.0% vs. 30.8%, P<0.001) than those with failure. Non-gastric MALT lymphoma patients showed worse prognosis compared to gastric cases. As for remission rates in patients with gastric MALT lymphoma, successful H. pylori eradication therapy could be a good prognostic factor even if H. pylori infection was present at diagnosis.

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review

PubMed Central

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan

2018-01-01

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections. PMID:29438279

Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature

PubMed Central

Zhu, Xingjun; Feng, Wei; Chang, Jian; Tan, Yan-Wen; Li, Jiachang; Chen, Min; Sun, Yun; Li, Fuyou

2016-01-01

Photothermal therapy (PTT) at present, following the temperature definition for conventional thermal therapy, usually keeps the temperature of lesions at 42–45 °C or even higher. Such high temperature kills cancer cells but also increases the damage of normal tissues near lesions through heat conduction and thus brings about more side effects and inhibits therapeutic accuracy. Here we use temperature-feedback upconversion nanoparticle combined with photothermal material for real-time monitoring of microscopic temperature in PTT. We observe that microscopic temperature of photothermal material upon illumination is high enough to kill cancer cells when the temperature of lesions is still low enough to prevent damage to normal tissue. On the basis of the above phenomenon, we further realize high spatial resolution photothermal ablation of labelled tumour with minimal damage to normal tissues in vivo. Our work points to a method for investigating photothermal properties at nanoscale, and for the development of new generation of PTT strategy. PMID:26842674

Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration.

PubMed

Chávez, Myra Noemi; Schenck, Thilo Ludwig; Hopfner, Ursula; Centeno-Cerdas, Carolina; Somlai-Schweiger, Ian; Schwarz, Christian; Machens, Hans-Günther; Heikenwalder, Mathias; Bono, María Rosa; Allende, Miguel L; Nickelsen, Jörg; Egaña, José Tomás

2016-01-01

The use of artificial tissues in regenerative medicine is limited due to hypoxia. As a strategy to overcome this drawback, we have shown that photosynthetic biomaterials can produce and provide oxygen independently of blood perfusion by generating chimeric animal-plant tissues during dermal regeneration. In this work, we demonstrate the safety and efficacy of photosynthetic biomaterials in vivo after engraftment in a fully immunocompetent mouse skin defect model. Further, we show that it is also possible to genetically engineer such photosynthetic scaffolds to deliver other key molecules in addition to oxygen. As a proof-of-concept, biomaterials were loaded with gene modified microalgae expressing the angiogenic recombinant protein VEGF. Survival of the algae, growth factor delivery and regenerative potential were evaluated in vitro and in vivo. This work proposes the use of photosynthetic gene therapy in regenerative medicine and provides scientific evidence for the use of engineered microalgae as an alternative to deliver recombinant molecules for gene therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

A bird's-eye view of cell therapy and tissue engineering for cardiac regeneration.

PubMed

Soler-Botija, Carolina; Bagó, Juli R; Bayes-Genis, Antoni

2012-04-01

Complete recovery of ischemic cardiac muscle after myocardial infarction is still an unresolved concern. In recent years, intensive research efforts have focused on mimicking the physical and biological properties of myocardium for cardiac repair. Here we show how heart regeneration approaches have evolved from cell therapy to refined tissue engineering. Despite progressive improvements, the best cell type and delivery strategy are not well established. Our group has identified a new population of cardiac adipose tissue-derived progenitor cells with inherent cardiac and angiogenic potential that is a promising candidate for cell therapy to restore ischemic myocardium. We also describe results from three strategies for cell delivery into a murine model of myocardial infarction: intramyocardial injection, implantation of a fibrin patch loaded with cells, and an engineered bioimplant (a combination of chemically designed scaffold, peptide hydrogel, and cells); dual-labeling noninvasive bioluminescence imaging enables in vivo monitoring of cardiac-specific markers and cell survival. © 2012 New York Academy of Sciences.

Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature.

PubMed

Zhu, Xingjun; Feng, Wei; Chang, Jian; Tan, Yan-Wen; Li, Jiachang; Chen, Min; Sun, Yun; Li, Fuyou

2016-02-04

Photothermal therapy (PTT) at present, following the temperature definition for conventional thermal therapy, usually keeps the temperature of lesions at 42-45 °C or even higher. Such high temperature kills cancer cells but also increases the damage of normal tissues near lesions through heat conduction and thus brings about more side effects and inhibits therapeutic accuracy. Here we use temperature-feedback upconversion nanoparticle combined with photothermal material for real-time monitoring of microscopic temperature in PTT. We observe that microscopic temperature of photothermal material upon illumination is high enough to kill cancer cells when the temperature of lesions is still low enough to prevent damage to normal tissue. On the basis of the above phenomenon, we further realize high spatial resolution photothermal ablation of labelled tumour with minimal damage to normal tissues in vivo. Our work points to a method for investigating photothermal properties at nanoscale, and for the development of new generation of PTT strategy.

ECM and ECM-like materials - Biomaterials for applications in regenerative medicine and cancer therapy.

PubMed

Hinderer, Svenja; Layland, Shannon Lee; Schenke-Layland, Katja

2016-02-01

Regenerative strategies such as stem cell-based therapies and tissue engineering applications are being developed with the aim to replace, remodel, regenerate or support damaged tissues and organs. In addition to careful cell type selection, the design of appropriate three-dimensional (3D) scaffolds is essential for the generation of bio-inspired replacement tissues. Such scaffolds are usually made of degradable or non-degradable biomaterials and can serve as cell or drug carriers. The development of more effective and efficient drug carrier systems is also highly relevant for novel cancer treatment strategies. In this review, we provide a summary of current approaches that employ ECM and ECM-like materials, or ECM-synthetic polymer hybrids, as biomaterials in the field of regenerative medicine. We further discuss the utilization of such materials for cell and drug delivery, and highlight strategies for their use as vehicles for cancer therapy. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Hyaluronic Acid: A Boon in Periodontal Therapy

PubMed Central

Dahiya, Parveen; Kamal, Reet

2013-01-01

Hyaluronic acid is a naturally occurring linear polysaccharide of the extracellular matrix of connective tissue, synovial fluid, and other tissues. Its use in the treatment of the inflammatory process is established in medical areas such as orthopedics, dermatology, and ophthalmology. The Pubmed/Medline database was searched for keywords “Hyaluronic acid and periodontal disease” and “Hyaluronic acid and gingivitis” which resulted in 89 and 22 articles respectively. Only highly relevant articles from electronic and manual search in English literature were selected for the present review article. In the field of dentistry, hyaluronic acid has shown anti-inflammatory and anti-bacterial effects in the treatment of periodontal diseases. Due to its tissue healing properties, it could be used as an adjunct to mechanical therapy in the treatment of periodontitis. Further studies are required to determine the clinical efficacy of hyaluronic acid in healing of periodontal lesion. The aim of the present review, article is to discuss the role of hyaluronic acid in periodontal therapy. PMID:23814761

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector-p53.

PubMed

Baliaka, A; Zarogoulidis, P; Domvri, K; Hohenforst-Schmidt, W; Sakkas, A; Huang, H; Le Pivert, P; Koliakos, G; Koliakou, E; Kouzi-Koliakos, K; Tsakiridis, K; Chioti, A; Siotou, E; Cheva, A; Zarogoulidis, K; Sakkas, L

2014-02-01

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

SU-G-TeP3-09: Proton Minibeam Radiation Therapy Increases Normal Tissue Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prezado, Y; Gonzalez-Infantes, W; Juchaux, M

Purpose: The dose tolerances of normal tissues continue being the main limitation in radiotherapy. To overcome it, we recently proposed a novel concept: proton minibeam radiation therapy (pMBRT) [1]. It allies the physical advantages of protons with the normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams (minibeam radiation therapy) [2]. The dose distributions are such that the tumor receives a homogeneous dose distribution, while normal tissues benefit from the spatial fractionation of the dose. The objective of our work was to implement this promising technique at a clinical center (Proton therapy center in Orsay) in order tomore » evaluate the potential gain in tissue sparing. Methods: Dose distributions were measured by means of gafchromic films and a PTW microdiamond detector (60019). Once the dosimetry was established, the whole brain of 7 weeks old male Fischer 344 rats was irradiated. Half of the animals received conventional seamless proton irradiation (25 Gy in one fraction). The other rats were irradiated with pMBRT (58 Gy peak dose in one fraction). The average dose deposited in the same targeted volume was in both cases 25 Gy. Results: The first complete set of dosimetric data in such small proton field sizes was obtained [3]. Rats treated with conventional proton irradiation exhibited severe moist desquamation and permanent epilation afterwards. The minibeam group, on the other hand, exhibited no skin damage and no clinical symptoms. MRI imaging and histological analysis are planned at 6 months after irradiation. Conclusion: Our preliminary results indicate that pMBRT leads to an increase in tissue resistance. This can open the door to an efficient treatment of very radioresistant tumours. [1] Prezado et al. Med. Phys. 40, 031712, 1–8 (2013).[2] Prezado et al., Rad. Research. 184, 314-21 (2015). [3] Peucelle et al., Med. Phys. 42 7108-13 (2015).« less

Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure

PubMed Central

Peck, Amy R.; Witkiewicz, Agnieszka K.; Liu, Chengbao; Stringer, Ginger A.; Klimowicz, Alexander C.; Pequignot, Edward; Freydin, Boris; Tran, Thai H.; Yang, Ning; Rosenberg, Anne L.; Hooke, Jeffrey A.; Kovatich, Albert J.; Nevalainen, Marja T.; Shriver, Craig D.; Hyslop, Terry; Sauter, Guido; Rimm, David L.; Magliocco, Anthony M.; Rui, Hallgeir

2011-01-01

Purpose To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. Patients and Methods Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. Results Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). Conclusion Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy. PMID:21576635

Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 2: Reconstruction of Lacrimal Gland Tissue: What Has Been Achieved So Far and What Are the Remaining Challenges?

PubMed

Massie, Isobel; Dietrich, Jana; Roth, Mathias; Geerling, Gerd; Mertsch, Sonja; Schrader, Stefan

2016-10-01

The lacrimal gland is located in the upper temporal compartment of the orbita, and along with the ocular surface, eye lids, and sensory and motor nerves forms the lacrimal functional unit (LFU). The LFU is responsible for producing, distributing, and maintaining the tear film in order to maintain a smooth, moist, and regular ocular surface epithelium such that appropriate refractive properties are achieved and the eyeball is protected against dust, debris, and pathogens. If the main lacrimal gland is impaired (due to either disease or injury), this balance is disrupted, and severe quantitative dry eye syndrome (DES) can develop. DES treatments remain palliative, with the most commonly used therapies being based on tear substitution, tear retention, and control of inflammation on the ocular surface. Causative treatments such as salivary gland transplantation have shown to reduce symptoms in very severe cases, however can cause problems on the ocular surface due to different properties of saliva and tears. Therefore, causative approaches for treating DES by regeneration or reconstruction of lacrimal gland tissue depending on disease severity seem highly appealing. This article reviews current approaches for in vitro reconstruction of lacrimal gland tissue. Finally, the limitations that must be overcome before a new, tissue-engineered therapy may be delivered to clinic will be discussed.

A Prototype Therapy System for Transcutaneous Application of Boiling Histotripsy.

PubMed

Maxwell, Adam D; Yuldashev, Petr V; Kreider, Wayne; Khokhlova, Tatiana D; Schade, George R; Hall, Timothy L; Sapozhnikov, Oleg A; Bailey, Michael R; Khokhlova, Vera A

2017-10-01

Boiling histotripsy (BH) is a method of focused ultrasound surgery that noninvasively applies millisecond-length pulses with high-amplitude shock fronts to generate liquefied lesions in tissue. Such a technique requires unique outputs compared to a focused ultrasound thermal therapy apparatus, particularly to achieve high in situ pressure levels through intervening tissue. This paper describes the design and characterization of a system capable of producing the necessary pressure to transcutaneously administer BH therapy through clinically relevant overlying tissue paths using pulses with duration up to 10 ms. A high-voltage electronic pulser was constructed to drive a 1-MHz focused ultrasound transducer to produce shock waves with amplitude capable of generating boiling within the pulse duration in tissue. The system output was characterized by numerical modeling with the 3-D Westervelt equation using boundary conditions established by acoustic holography measurements of the source field. Such simulations were found to be in agreement with directly measured focal waveforms. An existing derating method for nonlinear therapeutic fields was used to estimate in situ pressure levels at different tissue depths. The system was tested in ex vivo bovine liver samples to create BH lesions at depths up to 7 cm. Lesions were also created through excised porcine body wall (skin, adipose, and muscle) with 3-5 cm thickness. These results indicate that the system is capable of producing the necessary output for transcutaneous ablation with BH.

Cryopreservation Method for the Effective Collection of Dental Pulp Stem Cells.

PubMed

Takebe, Yusuke; Tatehara, Seiko; Fukushima, Tatsuhiro; Tokuyama-Toda, Reiko; Yasuhara, Rika; Mishima, Kenji; Satomura, Kazuhito

2017-05-01

Dental pulp stem cells (DPSCs) are an attractive cell source for use in cell-based therapy, regenerative medicine, and tissue engineering because DPSCs have a high cell proliferation ability and multidifferentiation capacity. However, several problems are associated with the collection and preservation of DPSCs for use in future cell-based therapy. In particular, the isolation of DPSCs for cryopreservation is time consuming and expensive. In this study, we developed a novel cryopreservation method (NCM) for dental pulp tissues to isolate suitable DPSCs after thawing cryopreserved tissue. Using the NCM, dental pulp tissues were cultured on adhesion culture dishes for 5 days and then cryopreserved. After thawing, the cryopreserved dental pulp tissue fragments exhibited cell migration. We evaluated each property of DPSCs isolated using the NCM (DPSCs-NCM) and the explant method alone without cryopreservation (DPSCs-C). DPSCs-NCM had the same proliferation capacity as DPSCs-C. Flow cytometry (FACS) analysis indicated that both DPSCs-NCM and DPSCs-C were positive for mesenchymal stem cell markers at the same level but negative for hematopoietic cell markers. Moreover, both DPSCs-NCM and DPSCs-C could differentiate into osteogenic, chondrogenic, and adipogenic cells during culture in each induction medium. These results suggest that DPSCs-NCM may be mesenchymal stem cells. Therefore, our novel method might facilitate the less expensive cryopreservation of DPSCs, thereby providing suitable DPSCs for use in patients in future cell-based therapies.

Dental pulp stem cells as a multifaceted tool for bioengineering and the regeneration of craniomaxillofacial tissues

PubMed Central

Aurrekoetxea, Maitane; Garcia-Gallastegui, Patricia; Irastorza, Igor; Luzuriaga, Jon; Uribe-Etxebarria, Verónica; Unda, Fernando; Ibarretxe, Gaskon

2015-01-01

Dental pulp stem cells, or DPSC, are neural crest-derived cells with an outstanding capacity to differentiate along multiple cell lineages of interest for cell therapy. In particular, highly efficient osteo/dentinogenic differentiation of DPSC can be achieved using simple in vitro protocols, making these cells a very attractive and promising tool for the future treatment of dental and periodontal diseases. Among craniomaxillofacial organs, the tooth and salivary gland are two such cases in which complete regeneration by tissue engineering using DPSC appears to be possible, as research over the last decade has made substantial progress in experimental models of partial or total regeneration of both organs, by cell recombination technology. Moreover, DPSC seem to be a particularly good choice for the regeneration of nerve tissues, including injured or transected cranial nerves. In this context, the oral cavity appears to be an excellent testing ground for new regenerative therapies using DPSC. However, many issues and challenges need yet to be addressed before these cells can be employed in clinical therapy. In this review, we point out some important aspects on the biology of DPSC with regard to their use for the reconstruction of different craniomaxillofacial tissues and organs, with special emphasis on cranial bones, nerves, teeth, and salivary glands. We suggest new ideas and strategies to fully exploit the capacities of DPSC for bioengineering of the aforementioned tissues. PMID:26528190

Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia

PubMed Central

Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

2015-01-01

This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy. PMID:26712750

Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

PubMed Central

Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

1995-01-01

Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

Combining manual therapy with pain neuroscience education in the treatment of chronic low back pain: A narrative review of the literature.

PubMed

Puentedura, Emilio J; Flynn, Timothy

2016-07-01

Teaching people with chronic low back pain (CLBP) about the neurobiology and neurophysiology of their pain is referred to as pain neuroscience education (PNE). There is growing evidence that when PNE is provided to patients with chronic musculoskeletal pain, it can result in decreased pain, pain catastrophization, disability, and improved physical performance. Because the aim of PNE is to shift the patient's focus from the tissues in the low back as the source of their pain to the brain's interpretation of inputs, many clinicians could mistakenly believe that PNE should be a "hands-off," education-only approach. An argument can be made that by providing manual therapy or exercise to address local tissue pathology, the patient's focus could be brought back to the low back tissues as the source of their problem. In this narrative literature review, we present the case for a balanced approach that combines PNE with manual therapy and exercise by considering how manual therapy can also be incorporated for interventions with patients with CLBP. We propose that as well as producing local mechanical effects, providing manual therapy within a PNE context can be seen as meeting or perhaps enhancing patient expectations, and also refreshing or sharpening body schema maps within the brain. Ideally, all of this should lead to better outcomes in patients with CLBP.

Progress towards genetic and pharmacological therapies for keratin genodermatoses: current perspective and future promise

PubMed Central

Chamcheu, Jean Christopher; Wood, Gary S.; Siddiqui, Imtiaz A.; Syed, Deeba N.; Adhami, Vaqar M.; Teng, Joyce M.; Mukhtar, Hasan

2012-01-01

Hereditary keratin disorders of the skin and its appendages comprise a large group of clinically heterogeneous disfiguring blistering and ichthyotic diseases, primarily characterized by the loss of tissue integrity, blistering and hyperkeratosis in severely affected tissues. Pathogenic mutations in keratins cause these afflictions. Typically, these mutations in concert with characteristic features have formed the basis for improved disease diagnosis, prognosis and most recently therapy development. Examples include epidermolysis bullosa simplex, keratinopathic ichthyosis, pachyonychia congenita and several other tissue-specific hereditary keratinopathies. Understanding the molecular and genetic events underlying skin dysfunction has initiated alternative treatment approaches that may provide novel therapeutic opportunities for affected patients. Animal and in vitro disease modelling studies have shed more light on molecular pathogenesis, further defining the role of keratins in disease processes and promoting the translational development of new gene and pharmacological therapeutic strategies. Given that the molecular basis for these monogenic disorders is well established, gene therapy and drug discovery targeting pharmacological compounds with the ability to reinforce the compromised cytoskeleton may lead to promising new therapeutic strategies for treating hereditary keratinopathies. In this review, we will summarize and discuss recent advances in the preclinical and clinical modelling and development of gene, natural product, pharmacological and protein-based therapies for these disorders, highlighting the feasibility of new approaches for translational clinical therapy. PMID:22716242

Progress towards genetic and pharmacological therapies for keratin genodermatoses: current perspective and future promise.

PubMed

Chamcheu, Jean Christopher; Wood, Gary S; Siddiqui, Imtiaz A; Syed, Deeba N; Adhami, Vaqar M; Teng, Joyce M; Mukhtar, Hasan

2012-07-01

Hereditary keratin disorders of the skin and its appendages comprise a large group of clinically heterogeneous disfiguring blistering and ichthyotic diseases, primarily characterized by the loss of tissue integrity, blistering and hyperkeratosis in severely affected tissues. Pathogenic mutations in keratins cause these afflictions. Typically, these mutations in concert with characteristic features have formed the basis for improved disease diagnosis, prognosis and most recently therapy development. Examples include epidermolysis bullosa simplex, keratinopathic ichthyosis, pachyonychia congenita and several other tissue-specific hereditary keratinopathies. Understanding the molecular and genetic events underlying skin dysfunction has initiated alternative treatment approaches that may provide novel therapeutic opportunities for affected patients. Animal and in vitro disease modelling studies have shed more light on molecular pathogenesis, further defining the role of keratins in disease processes and promoting the translational development of new gene and pharmacological therapeutic strategies. Given that the molecular basis for these monogenic disorders is well established, gene therapy and drug discovery targeting pharmacological compounds with the ability to reinforce the compromised cytoskeleton may lead to promising new therapeutic strategies for treating hereditary keratinopathies. In this review, we will summarize and discuss recent advances in the preclinical and clinical modelling and development of gene, natural product, pharmacological and protein-based therapies for these disorders, highlighting the feasibility of new approaches for translational clinical therapy. © 2012 John Wiley & Sons A/S.

Standard and Nonstandard Craniospinal Radiotherapy Using Helical TomoTherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, William, E-mail: william@medphys.mcgill.c; Brodeur, Marylene; Roberge, David

2010-07-01

Purpose: To show the advantages of planning and delivering craniospinal radiotherapy with helical TomoTherapy (TomoTherapy Inc., Madison, WI) by presenting 4 cases treated at our institution. Methods and Materials: We first present a standard case of craniospinal irradiation in a patient with recurrent myxopapillary ependymoma (MPE) and follow this with 2 cases requiring differential dosing to multiple target volumes. One of these, a patient with recurrent medulloblastoma, required a lower dose to be delivered to the posterior fossa because the patient had been previously irradiated to the full dose, and the other required concurrent boosts to leptomeningeal metastases as partmore » of his treatment for newly diagnosed MPE. The final case presented is a patient with pronounced scoliosis who required spinal irradiation for recurrent MPE. Results: The four cases presented were planned and treated successfully with Helical Tomotherapy. Conclusions: Helical TomoTherapy delivers continuous arc-based intensity-modulated radiotherapy that gives high conformality and excellent dose homogeneity for the target volumes. Increased healthy tissue sparing is achieved at higher doses albeit at the expense of larger volumes of tissue receiving lower doses. Helical TomoTherapy allows for differential dosing of multiple targets, resulting in very elegant dose distributions. Daily megavoltage computed tomography imaging allows for precision of patient positioning, permitting a reduction in planning margins and increased healthy tissue sparing in comparison with standard techniques.« less

Infrared photobiomodulation (PBM) therapy improves glucose metabolism and intracellular insulin pathway in adipose tissue of high-fat fed mice.

PubMed

Silva, Gabriela; Ferraresi, Cleber; de Almeida, Rodrigo Teixeira; Motta, Mariana Lopes; Paixão, Thiago; Ottone, Vinicius Oliveira; Fonseca, Ivana Alice; Oliveira, Murilo Xavier; Rocha-Vieira, Etel; Dias-Peixoto, Marco Fabrício; Esteves, Elizabethe Adriana; Coimbra, Cândido Celso; Amorim, Fabiano Trigueiro; de Castro Magalhães, Flávio

2018-04-01

Obesity represents a continuously growing global epidemic and is associated with the development of type 2 diabetes mellitus. The etiology of type 2 diabetes is related to the resistance of insulin-sensitive tissues to its action leading to impaired blood glucose regulation. Photobiomodulation (PBM) therapy might be a non-pharmacological, non-invasive strategy to improve insulin resistance. It has been reported that PBM therapy in combination with physical exercise reduces insulin resistance. Therefore, the aim of this study was to investigate the effects of PBM therapy on insulin resistance in obese mice. Male Swiss albino mice received low-fat control diet (n = 16, LFC) or high-fat diet (n = 18, HFD) for 12 weeks. From 9th to 12th week, the mice received PBM therapy (LASER) or Sham (light off) treatment and were allocated into four groups: LFC Sham (n = 8), LFC PBM (n = 8), HFD Sham (n = 9), and HFD PBM (n = 9). The PBM therapy was applied in five locations: to the left and right quadriceps muscle, upper limbs and center of the abdomen, during 40 s at each point, once a day, 5 days a week, for 4 weeks (780 nm, 250 mW/cm 2 , 10 J/cm 2 , 0.4 J per site; 2 J total dose per day). Insulin signaling pathway was evaluated in the epididymal adipose tissue. PBM therapy improved glucose tolerance and phosphorylation of Akt (Ser473) and reversed the HFD-induced reduction of GLUT4 content and phosphorylation of AS160 (Ser588). Also, PBM therapy reversed the increased area of epididymal and mesenteric adipocytes. The results showed that chronic PBM therapy improved parameters related to obesity and insulin resistance in HFD-induced obesity in mice.

Sports medicine and platelet-rich plasma: nonsurgical therapy.

PubMed

Grambart, Sean T

2015-01-01

A Cochrane Review was performed to assess the effects of platelet-rich therapies for treating musculoskeletal soft tissue injuries. Selection criteria were randomized and quasirandomized controlled trials (RCTs) that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling, or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain, and adverse effects. The investigators found 19 studies that compared platelet-rich therapy with placebo, autologous whole blood, dry needling, or no platelet-rich therapy. Disorders included rotator cuff tears (arthroscopic repair; 6 trials); shoulder impingement syndrome surgery (1 trial); elbow epicondylitis (3 trials); anterior cruciate ligament (ACL) reconstruction (4 trials), ACL reconstruction (donor graft site application; 2 trials), patellar tendinopathy (1 trial), Achilles tendinopathy (1 trial), and acute Achilles rupture surgical repair (1 trial). They further subdivided the studies based on type of treatment, including tendinopathies in which platelet-rich therapy injections were the main treatment (5 trials), and surgical augmentation procedures in which platelet-rich therapy was applied during surgery (14 trials). The conclusion was that there is currently insufficient evidence to support the use of platelet-rich therapy for treating musculoskeletal soft tissue injuries. Researchers contemplating RCTs should consider the coverage of currently ongoing trials when assessing the need for future RCTs on specific conditions. There is a need for standardization of PRP preparation methods. At this time, the use of PRP in foot and ankle surgery as an orthobiologic does not have an absolute indication. Many of the studies are lower evidence-based from surgical techniques. Several in vitro studies have shown that growth factors promote the regeneration of bone, cartilage, and tendons. More clinical studies are needed to evaluate the use of PRP as an orthobiologic. In the author’s opinion, PRP does have a role when conservative treatment has failed and the next treatment option is an invasive surgical procedure Copyright © 2015 Elsevier Inc. All rights reserved.

Subarachnoid-to-Subarachnoid Shunt for Correction of Nonfunctioning Baclofen Pump in a Severe Case of Chronic Debilitating Post-Spinal Cord Injury Spasticity.

PubMed

Bakare, Adewale A; Weyhenmeyer, Jonathan; Lee, Albert

2018-02-01

Perhaps the most disabling condition seen in patients with spinal cord injury (SCI) is spasticity. Spasticity is characterized as hyperreflexia and hypertonicity as a result of damage to the supraspinal tracts in the aftermath of SCI. Intrathecal baclofen (ITB) is the mainstay therapy for spasticity unresponsive to oral baclofen. One of the problems associated with post-SCI spasticity unresponsive to ITB is the development of scar tissue that prevents the diffusion of baclofen in the desired spinal cord area. This case offers a unique strategy to deal with multilevel scar tissue. This 46-year-old paraplegic male with a T8 SCI whose spasticity had been well managed with ITB therapy for many years recently suffered intractable spasticity necessitating multiple reoperations for a nonfunctioning ITB catheter secondary to extensive scar tissue and intrathecal adhesions. Placement of a subarachnoid-to-subarachnoid shunt eliminated the problem of extensive scar tissue preventing adequate baclofen therapy. After undergoing multilevel thoracic and lumbar laminectomies with subarachnoid-to-subarachnoid spinal shunt, the patient's spasticity was finally brought under control with adequate daily baclofen infusion. This case demonstrates a creative way to address ITB catheter failure before considering other measures, such as neuroablative procedures (e.g., rhizotomy, myelotomy). This case reinforces the recommendation that ablative procedures, which have far greater complications, should be reserved for patients who have failed medical or other nonablative therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of tension-type headache with articulatory and suboccipital soft tissue therapy: A double-blind, randomized, placebo-controlled clinical trial.

PubMed

Espí-López, Gemma V; Gómez-Conesa, Antonia; Gómez, Anna Arnal; Martínez, Josep Benítez; Pascual-Vaca, Angel Oliva; Blanco, Cleofás Rodríguez

2014-10-01

This study researches the effectiveness of two manual therapy treatments focused on the suboccipital region for tension-type headache. A randomized double-blind clinical trial was conducted over a period of four weeks with a follow-up at one month. Eighty-four patients with a mean age of 39.7 years (SD 11.4) with tension-type headache were assigned to 4 groups which included the following manual therapy treatment: suboccipital soft tissue inhibition; occiput-atlas-axis global manipulation; combination of both techniques; and a control group. The primary assessment consisted of collecting socio-demographic data and headache characteristics in a one-month base period, data such as age, gender, severity of pain, intensity and frequency of headache, among other. Outcome secondary assessment were: impact of headache, disability, ranges of motion of the craniocervical junction, frequency and intensity of headache, and pericranial tenderness. In the month prior to the study, average pain intensity, was rated at 6.49 (SD 1.69), and 66.7% subjects suffered headaches of moderate intensity. After 8 weeks, statistically significant improvements were noted. OAA manipulative treatment and combined therapy treatments proved to be more effective than suboccipital soft tissue inhibition for tension-type headache. The treatment with suboccipital soft tissue inhibition, despite producing less significant results, also has positive effects on different aspects of headache. Copyright © 2014 Elsevier Ltd. All rights reserved.

Principles of definitive soft tissue coverage with flaps.

PubMed

Levin, L Scott

2008-01-01

Despite the emergence of negative pressure wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by V.A.C.(R) Therapy (KCI, San Antonio, TX) for orthopaedic trauma, vascularized tissue transfer whether it be pedicle, free, or tissue transfer using the operating microscope or as an island, remains the mainstay of soft tissue reconstruction for orthopaedic traumatology. The critisism of microvascular procedures has been that they are lengthy, costly, and required technical expertise to perform. While technical skills are required, microsurgical care has evolved into a routine operation with high degrees of success in experienced hand. The problem that still remains is access to surgeons who are interested in soft tissue reconstruction and can perform definitive coverage with flaps. There is a need in the orthopaedic community to solve the problem of lack of flap surgeons and as a result, NPWT/ROCF has been touted as the answer to flap reconstruction. NPWT/ROCF is an important addition to soft tissue reconstruction but it serves as a bridge rather than definitive coverage in many hands. Just as wound technology is evolving with tissue substitutes, growth factors and NPWT/ROCF flaps technology continues to advance with new perforator flaps and local regional flaps, particularly the sural flap, coming on line as mainstays of soft tissue reconstruction.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog

PubMed Central

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

Introduction The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. Materials and methods GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. Results GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. Conclusion The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy. PMID:29713167

Metalloporphyrins and their uses as radiosensitizers for radiation therapy

DOEpatents

Miura, Michiko; Slatkin, Daniel N.

2004-07-06

The present invention covers radiosensitizers containing as an active ingredient halogenated derivatives of boronated porphyrins containing multiple carborane cages having the structure ##STR1## which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies including, but not limited to, boron neutron--capture therapy and photodynamic therapy. The present invention also covers methods for using these radiosensitizers in tumor imaging and cancer treatment.

Versatile graphene biosensors for enhancing human cell therapy.

PubMed

Vlăsceanu, George M; Amărandi, Roxana-Maria; Ioniță, Mariana; Tite, Teddy; Iovu, Horia; Pilan, Luisa; Burns, Jorge S

2018-05-01

Technological advances in engineering and cell biology stimulate novel approaches for medical treatment, in particular cell-based therapy. The first cell-based gene therapy against cancer was recently approved by the US Food and Drug Administration. Progress in cancer diagnosis includes a blood test detecting five cancer types. Numerous stem cell phase I/II clinical trials showing safety and efficacy will soon pursue qualifying criteria for advanced therapy medicinal products (ATMP), aspiring to join the first stem-cell therapy approved by the European Medicines Agency. Cell based therapy requires extensive preclinical characterisation of biomarkers indicating mechanisms of action crucial to the desired therapeutic effect. Quantitative analyses monitoring critical functions for the manufacture of optimal cell and tissue-based clinical products include successful potency assays for implementation. The challenge to achieve high quality measurement is increasingly met by progress in biosensor design. We adopt a cell therapy perspective to highlight recent examples of graphene-enhanced biointerfaces for measurement of biomarkers relevant to cancer treatment, diagnosis and tissue regeneration. Graphene based biosensor design problems can thwart their use for health care transformative point of care testing and real-time applications. We discuss concerns to be addressed and emerging solutions for establishing clinical grade biosensors to accelerate human cell therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

NASA Astrophysics Data System (ADS)

Fontenot, Jonas David

External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only weakly on uncertainties in the risk model and inter-patient variations. Second cancer risks were sensitive to changes in the RBE of neutrons. However, the findings of the study were qualitatively consistent for all patient sizes and risk models considered, and for all neutron RBE values less than 100.

Multimodal OCT for complex assessment of tumors response to therapy

NASA Astrophysics Data System (ADS)

Sirotkina, Marina A.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Zaitsev, Vladimir Yu.; Matveyev, Alexander L.; Shirmanova, Marina V.; Sovetsky, Alexander A.; Moiseev, Alexander A.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

2017-07-01

Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

Vaginal Speculum For Photodynamic Therapy And Method Of Using The Same

DOEpatents

Tadir, Yona; Berns, Michael W.; Monk, Brad J.; Profeta, Glen; Tromberg, Bruce J.

1995-10-17

An improved vaginal speculum for photodynamic therapy of intraepithelial tissue and in particular vaginal, cervical and vulvar neoplasia utilizes a precisely and accurately positionable optic fiber through which a predetermined dose of light in the range of 620 to 700 nanometers is delivered over a controlled area which has been previously treated with photodynamic therapeutic substances. In particular, the neoplastic area has been treated with hematoporphyrin derivatives and other photosensitizers which are selectively taken into the cancerous tissue. Exposure to the appropriate wavelength laser light photoactivates the absorbed hematoporphyrins causing the release of singlet oxygen which internally oxidizes and ultimately causes cell death. The fiber optic tip from which the laser light is transmitted is precisely positioned within the body cavity at a predetermined distance from the intraepithelial neoplasia in order to obtain the appropriate spot size and location to minimize damage to healthy tissue and maximize damage to the selectively impregnated cancerous tissue.

The effect of the shape and size of gold seeds irradiated with ultrasound on the bio-heat transfer in tissue.

PubMed

Gkigkitzis, Ioannis; Austerlitz, Carlos; Haranas, Ioannis; Campos, Diana

2015-01-01

The aim of this report is to propose a new methodology to treat prostate cancer with macro-rod-shaped gold seeds irradiated with ultrasound and develop a new computational method for temperature and thermal dose control of hyperthermia therapy induced by the proposed procedure. A computer code representation, based on the bio-heat diffusion equation, was developed to calculate the heat deposition and temperature elevation patterns in a gold rod and in the tissue surrounding it as a result of different therapy durations and ultrasound power simulations. The numerical results computed provide quantitative information on the interaction between high-energy ultrasound, gold seeds and biological tissues and can replicate the pattern observed in experimental studies. The effect of differences in shapes and sizes of gold rod targets irradiated with ultrasound is calculated and the heat enhancement and the bio-heat transfer in tissue are analyzed.

Evidence-based dentistry on laser paediatric dentistry: review and outlook.

PubMed

Olivi, G; Genovese, M D; Caprioglio, C

2009-03-01

The goal of paediatric dentistry is to provide preventive education to parents and patients as well as interception and therapy of dental diseases in a minimally invasive way using a stress-free approach. Different laser wavelengths are used for different applications following these minimally invasive concepts: argon, KTP, diode, Nd:YAG, and CO2 lasers are used for soft tissue applications and the erbium family is used for both soft and hard tissue procedures. This paper offers a revision and a discussion of the international literature, showing also some clinical procedures. related to these scientific studies. Soft tissues laser applications in Pediatric Dentistry include application in oral surgery as well as in periodontics and orthodontics. Laser applications on hard tissues include caries prevention and detection and application for sealing of pits and fissures. Also application for cavity preparation, carious removal and pulp therapy are discussed.

Lasers in oral surgery and implantology

NASA Astrophysics Data System (ADS)

Vescovi, Paolo

2016-03-01

The usefulness of laser for oral hard tissue procedure such as caries treatment, impacted teeth extraction, periodontal therapy, peri-implantitis management, sinus lifting is reported by several Authors [1]. Conventionally, mechanical rotary instruments and hand instruments are employed for bone surgery. Rotary instruments have better accessibility and cutting efficiency, but there is a risk of excessive heating of bone tissue and caution must be exercised to avoid the bur becoming entangled with surrounding soft tissues and the reflected flap. The main clinical advantages of the lasers are represented by minimal patient discomfort, good recovery with decreased or absent post-operative pain. In the last ten years are described in the international literature great advantages of Laser Surgery and Low Level Laser Therapy (LLLT) performed with different wavelength in addition to traditional surgical techniques to improve bone and soft tissue healing and for pain and infection control.

The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy.

PubMed

Nolan, David J; Rose, Rebecca; Rodriguez, Patricia H; Salemi, Marco; Singer, Elyse J; Lamers, Susanna L; McGrath, Michael S

2018-01-01

Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.

Tissue engineering and regenerative medicine: concepts for clinical application.

PubMed

Atala, Anthony

2004-01-01

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly given the aging population. Scientists in the field of regenerative medicine and tissue engineering apply the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. This paper reviews recent advances that have occurred in regenerative medicine and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

Engineering tissues, organs and cells.

PubMed

Atala, Anthony

2007-01-01

Patients suffering from diseased and injured organs may be treated with transplanted organs; however, there is a severe shortage of donor organs that is worsening yearly, given the ageing population. In the field of regenerative medicine and tissue engineering, scientists apply the principles of cell transplantation, materials science and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy, including the use of amniotic and placental fetal stem cells. This review covers recent advances that have occurred in regenerative medicine and describes applications of these technologies using chemical compounds that may offer novel therapies for patients with end-stage organ failure. 2007 John Wiley & Sons, Ltd

Combinatorial biomatrix/cell-based therapies for restoration of host tissue architecture and function

PubMed Central

Cantu, David Antonio; Kao, W. John

2014-01-01

This Progress Report reviews recent advances in the utility of extracellular matrix (ECM)-mimic biomaterials in presenting and delivering therapeutic cells to promote tissue healing. This overview gives a brief introduction of different cell types being used in regenerative medicine and tissue engineering while addressing critical issues that must be overcome before cell-based approaches can be routinely employed in the clinic. A selection of 5 commonly used cell-associated, biomaterial platforms (collagen, hyaluronic acid, fibrin, alginate, and poly(ethylene glycol)) are reviewed for treatment of a number of acute injury or diseases with emphasis on animal models and clinical trials. This article concludes with current challenges and future perspectives regarding foreign body host response to biomaterials and immunological reactions to allogeneic or xenogeneic cells, vascularization and angiogenesis, matching mechanical strength and anisotropy of native tissues, as well as other non-technical issues regarding the clinical translation of biomatrix/cell-based therapies. PMID:23828863

Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

PubMed

da Rocha, E L; Porto, L M; Rambo, C R

2014-01-01

Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

Minimally invasive ultrasound thermal therapy with MR thermal monitoring and guidance

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Stafford, R. Jason; Price, Roger E.; Nau, William H.; Tyreus, Per Daniel; Rivera, Belinda; Schomer, Donald; Olsson, Lars; Hazle, John D.

2001-06-01

In this study both transurethral and interstitial ultrasound thermal therapy were applied to thermally coagulate targeted portions of the canine prostate or brain and implanted TVT tumors while using MRI-based thermal mapping techniques to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. The complex phase-difference mapping technique using an iGE-EPI sequence with lipid suppression was used for determining temperature elevations within the in vivo prostate or brain and surrounding structures. Calculated temperature distributions, thermal dose exposures, T2-wieghted & T1-contrast enhanced images, gross inspection, and histology of sectioned prostates and brains were in good agreement with each other in defining destroyed tissue zones. Interstitial and transurethral ultrasound applicators produce directed zones of thermal coagulation within targeted tissue and implanted tumor, which can be accurately monitored and evaluated by MRI.

Changes in co-contraction during stair descent after manual therapy protocol in knee osteoarthritis: A pilot, single-blind, randomized study.

PubMed

Cruz-Montecinos, Carlos; Flores-Cartes, Rodrigo; Montt-Rodriguez, Agustín; Pozo, Esteban; Besoaín-Saldaña, Alvaro; Horment-Lara, Giselle

2016-10-01

Manual therapy has shown clinical results in patients with knee osteoarthritis. However, the biomechanical aspects during functional tasks have not been explored in depth. Through surface electromyography, the medial and lateral co-contractions of the knee were measured while descending stairs, prior and posterior to applying a manual therapy protocol in the knee, with emphasis on techniques of joint mobilization and soft-tissue management. Sixteen females with slight or moderate knee osteoarthritis were recruited (eight experimental, eight control). It was observed that the lateral co-contraction index of the experimental group, posterior to intervention, increased by 11.7% (p = 0.014). The application of a manual therapy protocol with emphasis on techniques of joint mobilization and soft-tissue management modified lateral co-contraction, which would have a protective effect on the joint. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hot topics in biomedical ultrasound: ultrasound therapy and its integration with ultrasonic imaging

NASA Astrophysics Data System (ADS)

Everbach, E. Carr

2005-09-01

Since the development of biomedical ultrasound imaging from sonar after WWII, there has been a clear divide between ultrasonic imaging and ultrasound therapy. While imaging techniques are designed to cause as little change as possible in the tissues through which ultrasound propagates, ultrasound therapy typically relies upon heating or acoustic cavitation to produce a desirable therapeutic effect. Concerns over the increasingly high acoustic outputs of diagnostic ultrasound scanners prompted the adoption of the Mechanical Index (MI) and Thermal Index (TI) in the early 1990s. Therapeutic applications of ultrasound, meanwhile, have evolved from deep tissue heating in sports medicine to include targeted drug delivery, tumor and plaque ablation, cauterization via high intensity focused ultrasound (HIFU), and accelerated dissolution of blood clots. The integration of ultrasonic imaging and therapy in one device is just beginning, but the promise of improved patient outcomes is balanced by regulatory and practical impediments.

High-intensity laser application in Orthodontics.

PubMed

Sant'Anna, Eduardo Franzotti; Araújo, Mônica Tirre de Souza; Nojima, Lincoln Issamu; Cunha, Amanda Carneiro da; Silveira, Bruno Lopes da; Marquezan, Mariana

2017-01-01

In dental practice, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) are mainly used for dental surgery and biostimulation therapy. Within the Orthodontic specialty, while LLLT has been widely used to treat pain associated with orthodontic movement, accelerate bone regeneration after rapid maxillary expansion, and enhance orthodontic tooth movement, HILT, in turn, has been seen as an alternative for addressing soft tissue complications associated to orthodontic treatment. The aim of this study is to discuss HILT applications in orthodontic treatment. This study describes the use of HILT in surgical treatments such as gingivectomy, ulotomy, ulectomy, fiberotomy, labial and lingual frenectomies, as well as hard tissue and other dental restorative materials applications. Despite the many applications for lasers in Orthodontics, they are still underused by Brazilian practitioners. However, it is quite likely that this demand will increase over the next years - following the trend in the USA, where laser therapies are more widely used.

Poster - Thurs Eve-16: Just-in-time tomography (JiTT).

PubMed

Pang, G; Rowlands, J A

2008-07-01

Soft-tissue target motion is one of the main concerns in high-precision radiation therapy. Cone beam computed tomography (CBCT) has been developed recently to image soft-tissue targets in the treatment room for image-guided radiation therapy. However, due to its relatively long image acquisition time the CBCT approach cannot provide images of the target at the instant of the treatment and thus is not adequate for imaging targets with intrafraction motion. In this work, a new concept for image-guided radiation therapy- just-in-time tomography (JiTT) - is introduced. Differing from CBCT, JiTT takes much less time to generate the needed tomographical, beam's-eye-view images of the treatment target at the right moment to guide the radiation therapy treatment. A system to achieve JiTT is proposed and its feasibility is investigated. Research supported by Siemens. © 2008 American Association of Physicists in Medicine.

Effect of Target Therapy on the Content of Transcription and Growth Factors, Protein Kinase TOR, and Activity of Intracellular Proteases in Patients with Metastatic Renal Cell Carcinoma.

PubMed

Spirina, L V; Usynin, E A; Kondakova, I V; Yurmazov, Z A; Slonimskaya, E M

2016-04-01

We analyzed the dynamics of the expression of transcription factors, VEGF and its receptor VEGFR2, serine-threonine protein kinase mTOR and activity of proteasome and calpain in patients with metastatic renal cancer during therapy with tyrosine kinase inhibitor Votrient and mTOR blocker Afinitor. The expression of hypoxic nuclear factor HIF-1α in the tumor tissue decreased during therapy with the target preparations. The decrease of VEGF and its receptor VEGFR2 was observed only in patients treated with mTOR inhibitor. The increase in calpain activity in the tumor tissue was observed in both groups. These findings extend our understanding of the mechanism of action of target anticancer preparations as allow considering the studied markers as predictors in choosing optimal therapy.

Successful limb salvage through staged bypass combined with free gracilis muscle transfer for critical limb ischemia with osteomyelitis after failed endovascular therapy.

PubMed

Miyake, Keisuke; Kikuchi, Shinsuke; Okuda, Hiroko; Koya, Atsuhiro; Abe, Satomi; Sawa, Yoshiki; Ota, Tetsuo; Azuma, Nobuyoshi

2018-05-02

Critical limb ischemia with osteomyelitis is so difficult to treat that even appropriate revascularization and wound therapy cannot achieve limb salvage because of uncontrollable infection. It is still difficult to judge the possibility of limb salvage before revascularization. A 73-year-old male complained of a small ulcer on his left toe, which was treated with multiple endovascular therapy. After failed endovascular therapy, he suffered extensive tissue loss with tibial osteomyelitis. We carried out staged surgery that was composed of dual bypass to the sural artery and posterior tibial artery. After intensive debridement and wound care, insertion of a subsequent free gracilis muscle flap to cover the exposed tibial bone was performed, achieving functional limb salvage. Even in the threatened limb with extensive tissue loss and osteomyelitis, intensive and multidisciplinary treatment with staged revascularization, muscle transfer, and appropriate wound care achieved functional limb salvage.

Effects of vascularization on cancer nanochemotherapy outcomes

NASA Astrophysics Data System (ADS)

Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

2016-08-01

Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

Physical therapy intervention for an adolescent with a knee flexion contracture and diagnosis of multiple pterygium syndrome.

PubMed

Bellamy, Sandra Gail; Gibbs, Karen; Lazaro, Rolando

2007-01-01

The purpose of this case report is to describe a course of physical therapy for a client with a rare genetic condition, multiple pterygium syndrome (MPS). MPS is a rare genetic disorder characterized by connective tissue webbing across multiple joints, dysmorphic facies, and various visceral and skeletal deformities. Before the patient commenced physical therapy, surgical amputation was recommended for the client's knee flexion contracture. The client's treatment plan included stretching, manual therapy, and resisted exercise. Long-term outcomes were decreased back and knee pain and improved range of motion, strength, and ambulation. Therapists using techniques to improve joint range of motion in clients with MPS should be aware that pterygia may include contractile tissue, nerves, and blood vessels and there may be underlying skeletal deformity or weakness in these areas. Children with MPS are at high risk of developing scoliosis and should be appropriately assessed in early childhood.

ON THE BENEFITS AND RISKS OF PROTON THERAPY IN PEDIATRIC CRANIOPHARYNGIOMA

PubMed Central

Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2013-01-01

Purpose Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm3, and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R2 values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not. PMID:21570209

The effect of individual antiretroviral drugs on body composition in HIV-infected persons initiating highly active antiretroviral therapy.

PubMed

Shlay, Judith C; Sharma, Shweta; Peng, Grace; Gibert, Cynthia L; Grunfeld, Carl

2009-07-01

To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ARTs assessed were as follows: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine, and abacavir. Skinfolds and circumferences were measured at baseline and every 4 months. Mid arm, mid thigh, and waist subcutaneous tissue areas and nonsubcutaneous tissue areas were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. d4T and ZDV use was associated with losses in subcutaneous tissue area and skinfold thickness. 3TC use was associated with gains in all subcutaneous tissue areas and skinfold thickness, whereas abacavir use was associated with an increase in waist subcutaneous tissue area. Indinavir was associated with gains in waist subcutaneous tissue area, whereas indinavir, efavirenz, and nevirapine were associated with increases in upper back skinfolds. d4T use was also associated with increases in all nonsubcutaneous tissue areas; 3TC use was associated with the greatest increase in waist nonsubcutaneous tissue area. In this prospective nonrandomized evaluation, the nucleoside reverse transcriptase inhibitors d4T and ZDV were associated with decreases in subcutaneous tissue areas, whereas 3TC use was associated with increased subcutaneous tissue areas and waist nonsubcutaneous tissue area.

Tissue engineering and regenerative medicine in applied research: a year in review of 2014.

PubMed

Lin, Xunxun; Huang, Jia; Shi, Yuan; Liu, Wei

2015-04-01

Tissue engineering and regenerative medicine (TERM) remains to be one of the fastest growing fields, which covers a wide scope of topics of both basic and applied biological researches. This overview article summarized the advancements in applied researches of TERM area, including stem cell-mediated tissue regeneration, material science, and TERM clinical trial. These achievements demonstrated the great potential of clinical regenerative therapy of tissue/organ disease or defect through stem cells and tissue engineering approaches.

The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

PubMed

Rafiq, Qasim A; Ortega, Ilida; Jenkins, Stuart I; Wilson, Samantha L; Patel, Asha K; Barnes, Amanda L; Adams, Christopher F; Delcassian, Derfogail; Smith, David

2015-11-01

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

[Role of angiotensin II receptor type 2 in predicting biochemical recurrence in the treatment of prostate cancer].

PubMed

Chibichyan, M B; Kogan, M I; Chernogubova, E A; Pavlenko, I A; Matishov, D G

2016-12-01

To identify markers for predicting aggressive forms of prostate cancer. The study retrospectively evaluated expression of angiotensin II type 2 receptors (AT2-R) in prostate needle biopsy tissue from patients with and without biochemical recurrence after combined hormone and radiation therapy. The study findings showed that low expression of AT2-R in prostate tissue was associated with a high risk of biochemical recurrence. The data on the nature of AT2-R expression in prostate tissue of prostate cancer patients may be considered as a tool for predicting biochemical recurrence after combined hormone and radiation therapy. The test has a sensitivity of 87.5% and specificity of 85.71%.

Effects of drugs on the efficacy of radioiodine (|) therapy in hyperthyroid patients.

PubMed

Oszukowska, Lidia; Knapska-Kucharska, Małgorzata; Lewiński, Andrzej

2010-03-01

The treatment of hyperthyroidism is targeted at reducing the production of thyroid hormones by inhibiting their synthesis or suppressing their release, as well as by controlling their influence on peripheral tissue (conservative therapy, medical treatment). Radical treatment includes surgical intervention to reduce the volume of thyroid tissue or damage of the mechanisms of thyroid hormone synthesis by radioiodine ((131)|) administration. Radioiodine ((131)|) is a reactor radionuclide, produced as a result of uranium decomposition and emission of β and γ radiation. The therapeutic effects of the isotope are obtained by the emission of β radiation. In the paper, the effects of administered drugs (antithyroid, glucocorticosteroids, lithium carbonate, inorganic iodine, β-blockers) on the final outcome of radioiodine therapy in patients with hyperthyroidism are discussed.

Orthodontics-surgical combination therapy for Class III skeletal malocclusion

PubMed Central

Ravi, M. S.; Shetty, Nillan K.; Prasad, Rajendra B.

2012-01-01

The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le – Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical–orthodontic combination therapy has resulted in near–normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level. PMID:22557903

Prodrug strategy for cancer cell-specific targeting: A recent overview.

PubMed

Zhang, Xian; Li, Xiang; You, Qidong; Zhang, Xiaojin

2017-10-20

The increasing development of targeted cancer therapy provides extensive possibilities in clinical trials, and numerous strategies have been explored. The prodrug is one of the most promising strategies in targeted cancer therapy to improve the selectivity and efficacy of cytotoxic compounds. Compared with normal tissues, cancer cells are characterized by unique aberrant markers, thus inactive prodrugs targeting these markers are excellent therapeutics to release active drugs, killing cancer cells without damaging normal tissues. In this review, we explore an integrated view of potential prodrugs applied in targeted cancer therapy based on aberrant cancer specific markers and some examples are provided for inspiring new ideas of prodrug strategy for cancer cell-specific targeting. Copyright © 2017. Published by Elsevier Masson SAS.

Clinical Ion Beam Applications: Basic Properties, Application, Quality Control, Planning

NASA Astrophysics Data System (ADS)

Kraft, Gerhard

2009-03-01

Heavy-ion therapy using beam scanning and biological dose optimization is a novel technique of high-precision external radiotherapy. It yields a better perspective for tumor cure of radio-resistant tumors. However, heavy-ion therapy is not a general solution for all types of tumors. As compared to conventional radiotherapy, heavy-ion radiotherapy has the advantages of higher tumor dose, improved sparing of normal tissue in the entrance channel, a more precise concentration of the dose in the target volume with steeper gradients to the normal tissue, and a higher radiobiological effectiveness for tumors which are radio-resistant in conventional therapy. These properties make it possible to treat radio-resistant tumors with great success, including those in close vicinity to critical organs.

Does an Algorithmic Approach to Using Brachytherapy and External Beam Radiation Result in Good Function, Local Control Rates, and Low Morbidity in Patients With Extremity Soft Tissue Sarcoma?

PubMed

Klein, Jason; Ghasem, Alex; Huntley, Samuel; Donaldson, Nathan; Keisch, Martin; Conway, Sheila

2018-03-01

High-dose-rate brachytherapy (HDR-BT) and external-beam radiation therapy (EBRT) are two modalities used in the treatment of soft tissue sarcoma. Previous work at our institution showed early complications and outcomes for patients treated with HDR-BT, EBRT, or a combination of both radiation therapy modalities. As the general indications for each of these approaches to radiation therapy differ, it is important to evaluate the use of each in an algorithmic way, reflecting how they are used in contemporary practice at sites that use these treatments. QUESTION/PURPOSES: (1) To determine the proportions of intermediate- and long-term complications associated with the use of brachytherapy in the treatment of primary high-grade extremity soft tissue sarcomas; (2), to characterize the long-term morbidity of the three radiation treatment groups using the Radiation Therapy Oncology Group/ European Organization for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Scoring Scheme; (3) to determine whether treatment with HDR-BT, EBRT, and HDR-BT+EBRT therapy, in combination with limb-salvage surgery, results in acceptable local control in this high-risk group of sarcomas. We retrospectively studied data from 171 patients with a diagnosis of high-grade extremity soft tissue sarcoma treated with limb-sparing surgery and radiation therapy between 1990 and 2012 at our institution, with a mean followup of 72 months. Of the 171 patients, 33 (20%) were treated with HDR-BT, 128 (75%) with EBRT, and 10 (6%) with HDR-BT+EBRT. We excluded 265 patients with soft tissue sarcomas owing to axial tumor location, previous radiation to the affected extremity, incomplete patient records, patients receiving primary amputation, recurrent tumors, pediatric patients, low- and intermediate-grade tumors, and rhabdoid histology. Fifteen patients (9%) were lost to followup for any reason including died of disease or other causes during the first 12 months postoperatively. This included four patients who received HDR-BT (12%), 11 who received EBRT (9%), and none who received HDR-BT+EBRT (0%) with less than 12 months followup. Determination of radiation therapy technique for each patient was individualized in a multidisciplinary forum of sarcoma specialists. Anticipated close or positive surgical margins and a low likelihood of complex soft tissue procedures were factors that encouraged use of brachytherapy, whereas the anticipated need for secondary procedures and/or soft tissue coverage encouraged use of EBRT alone. Combination therapy was used when the treatment volume exceeded the treatment field of the brachytherapy catheters or when the catheters were used to boost a close or positive surgical margin. Local recurrence, complications, and morbidity outcomes scores (RTOG) were calculated based on chart review. Between-group comparisons pertaining to the proportion of patients experiencing complications, morbidity outcomes scores, and local recurrence rates were not performed because of dissimilarities among the patients in each group at baseline. The HDR-BT treatment group showed a high incidence of intermediate-term complications, with the three most common being: deep infection (33%, 11 of 33); dehiscence and delayed wound healing (24%, eight of 33); and seroma and hematoma (21%, seven of 33). The EBRT group showed a high incidence of intermediate- and long-term complications with the three most common being: chronic radiation dermatitis (35%, 45 of 128); fibrosis (27%, 35 of 128); and chronic pain and neuritis (13%, 16 of 128). The RTOG scores for each treatment group were: HDR-BT 0.8 ± SD 1.2; EBRT 1.9 ± 2.0; and HDR-BT+EBRT 1.7 ± 1.7. Overall, 142 of 169 (84%) patients were free from local recurrence: 27 (82%) in the HDR-BT group, 108 (86%) in the EBRT group, and seven (70%) in the combination therapy group. In this single-institution study, an algorithmic approach to using HDR-BT and EBRT in the treatment of patients with high-grade soft tissue sarcomas can yield acceptable complication rates, good morbidity outcome scores, and a high degree of local control. Based on these results, we believe HDR-BT is best for patients with an anticipated close margin, a positive surgical margin, and for patients who are unlikely to receive a complex soft tissue procedure. Conversely, if a secondary procedure and/or soft tissue coverage are likely to be used, EBRT alone may be reasonable. Finally, combination therapy might be considered when the treatment volume exceeded the treatment field capacity for HDR-BT or when the catheters were used to boost a close or positive surgical margin. Level IV, therapeutic study.

Importance of tissue perfusion in ST segment elevation myocardial infarction patients undergoing reperfusion strategies: role of adenosine.

PubMed

Forman, Mervyn B; Jackson, Edwin K

2007-11-01

High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the "no-reflow" phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well-characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the "no reflow" phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri-reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6-month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the "no-reflow" phenomenon, support its use in high risk STEMI undergoing reperfusion.

Adjunctive use of the diode laser in non-surgical periodontal therapy: exploring the controversy.

PubMed

Porteous, Mary Sornborger; Rowe, Dorothy J

2014-04-01

Despite the controversy regarding clinical efficacy, dental hygienists use the diode laser as an adjunct to non-surgical periodontal therapy. The technique to maximize successful laser therapy outcome is controversial as well. The purpose of this review is to explore the scientific foundation of the controversy surrounding the use of the diode laser as an adjunct to non-surgical periodontal therapy. Further, this paper addresses the weaknesses in study design, the heterogeneity of methodology in the published clinical studies, especially the laser parameters, and how these issues impact the collective clinical and microbial data, and thus conclusions regarding clinical efficacy. Evaluation of the literature identifies possible mechanisms that could contribute to the varied, often conflicting results among laser studies that are the foundation of the controversy surrounding clinical efficacy. These mechanisms include current paradigms of periodontal biofilm behavior, tissue response to laser therapy being dependent on tissue type and health, and that the successful therapeutic treatment window is specific to the target tissue, biofilm composition, laser wavelength, and laser energy delivered. Lastly, this paper discusses laser parameters used in the various clinical studies, and how their diversity contributes to the controversy. Although this review does not establish clinical efficacy, it does reveal the scientific foundation of the controversy and the need for standardized, well designed randomized controlled clinical trials to develop specific guidelines for using the laser as an adjunct to non-surgical periodontal therapy. Using evidence-based laser guidelines would allow dental hygienists to provide more effective non-surgical periodontal care.

Equipoise among recanalization strategies.

PubMed

Tomsick, T A; Khatri, P; Jovin, T; Demaerschalk, B; Malisch, T; Demchuk, A; Hill, M D; Jauch, E; Spilker, J; Broderick, J P

2010-03-30

Modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable clinical outcomes. We outline key issues that we think underlie equipoise regarding the comparative clinical efficacy of IV recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial (IA) reperfusion therapies for acute ischemic stroke. On the one hand, IV rt-PA therapy has the benefit of speed with presumed lower rates of recanalization of large artery occlusions as compared to IA methods. More recent reports of major arterial occlusions treated with IV rt-PA, as measured by transcranial Doppler and magnetic resonance angiography, demonstrate higher rates of recanalization. Conversely, IA therapies report higher recanalization rates, but are hampered by procedural delays and risks, even failing to be applied at all in occasional patients where time to reperfusion remains a critical factor. Higher rates of recanalization in IA trials using clot-removal devices have not translated into improved patient functional outcome as compared to trials of IV therapy. Combined IV-IA therapy promises to offer advantages of both, but perhaps only when applied in the timeliest of fashions, compared to IV therapy alone. Where equipoise exists, randomizing subjects to either IV rt-PA therapy or IV therapy followed by IA intervention, while incorporating new interventions into the study design, is a rational and appropriate research approach.

Magnetic microspheres and tissue model studies for therapeutic applications

NASA Technical Reports Server (NTRS)

Ramachandran, Narayanan; Mazuruk, Konstantin

2004-01-01

The use of magnetic fluids and magnetic particles in combinatorial hyperthermia therapy for cancer treatment is reviewed. The investigation approach adopted for producing thermoregulating particles and tissue model studies for studying particle retention and heating characteristics is discussed.

Adult Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult soft tissue sarcoma (STS) treatment is determined by the tumor grade and may include surgery, radiation therapy, and/or chemotherapy. Get comprehensive information for newly diagnosed and recurrent STS and treatment in this summary for clinicians.

Regeneration and Repair in Endodontics—A Special Issue of the Regenerative Endodontics—A New Era in Clinical Endodontics

PubMed Central

Saoud, Tarek Mohamed A.; Ricucci, Domenico; Lin, Louis M.; Gaengler, Peter

2016-01-01

Caries is the most common cause of pulp-periapical disease. When the pulp tissue involved in caries becomes irreversibly inflamed and progresses to necrosis, the treatment option is root canal therapy because the infected or non-infected necrotic pulp tissue in the root canal system is not accessible to the host's innate and adaptive immune defense mechanisms and antimicrobial agents. Therefore, the infected or non-infected necrotic pulp tissue must be removed from the canal space by pulpectomy. As our knowledge in pulp biology advances, the concept of treatment of pulpal and periapical disease also changes. Endodontists have been looking for biologically based treatment procedures, which could promote regeneration or repair of the dentin-pulp complex destroyed by infection or trauma for several decades. After a long, extensive search in in vitro laboratory and in vivo preclinical animal experiments, the dental stem cells capable of regenerating the dentin-pulp complex were discovered. Consequently, the biological concept of ‘regenerative endodontics’ emerged and has highlighted the paradigm shift in the treatment of immature permanent teeth with necrotic pulps in clinical endodontics. Regenerative endodontics is defined as biologically based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as the pulp-dentin complex. According to the American Association of Endodontists’ Clinical Considerations for a Regenerative Procedure, the primary goal of the regenerative procedure is the elimination of clinical symptoms and the resolution of apical periodontitis. Thickening of canal walls and continued root maturation is the secondary goal. Therefore, the primary goal of regenerative endodontics and traditional non-surgical root canal therapy is the same. The difference between non-surgical root canal therapy and regenerative endodontic therapy is that the disinfected root canals in the former therapy are filled with biocompatible foreign materials and the root canals in the latter therapy are filled with the host's own vital tissue. The purpose of this article is to review the potential of using regenerative endodontic therapy for human immature and mature permanent teeth with necrotic pulps and/or apical periodontitis, teeth with persistent apical periodontitis after root canal therapy, traumatized teeth with external inflammatory root resorption, and avulsed teeth in terms of elimination of clinical symptoms and resolution of apical periodontitis. PMID:29563445

Regeneration and Repair in Endodontics-A Special Issue of the Regenerative Endodontics-A New Era in Clinical Endodontics.

PubMed

Saoud, Tarek Mohamed A; Ricucci, Domenico; Lin, Louis M; Gaengler, Peter

2016-02-27

Caries is the most common cause of pulp-periapical disease. When the pulp tissue involved in caries becomes irreversibly inflamed and progresses to necrosis, the treatment option is root canal therapy because the infected or non-infected necrotic pulp tissue in the root canal system is not accessible to the host's innate and adaptive immune defense mechanisms and antimicrobial agents. Therefore, the infected or non-infected necrotic pulp tissue must be removed from the canal space by pulpectomy. As our knowledge in pulp biology advances, the concept of treatment of pulpal and periapical disease also changes. Endodontists have been looking for biologically based treatment procedures, which could promote regeneration or repair of the dentin-pulp complex destroyed by infection or trauma for several decades. After a long, extensive search in in vitro laboratory and in vivo preclinical animal experiments, the dental stem cells capable of regenerating the dentin-pulp complex were discovered. Consequently, the biological concept of 'regenerative endodontics' emerged and has highlighted the paradigm shift in the treatment of immature permanent teeth with necrotic pulps in clinical endodontics. Regenerative endodontics is defined as biologically based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as the pulp-dentin complex. According to the American Association of Endodontists' Clinical Considerations for a Regenerative Procedure, the primary goal of the regenerative procedure is the elimination of clinical symptoms and the resolution of apical periodontitis. Thickening of canal walls and continued root maturation is the secondary goal. Therefore, the primary goal of regenerative endodontics and traditional non-surgical root canal therapy is the same. The difference between non-surgical root canal therapy and regenerative endodontic therapy is that the disinfected root canals in the former therapy are filled with biocompatible foreign materials and the root canals in the latter therapy are filled with the host's own vital tissue. The purpose of this article is to review the potential of using regenerative endodontic therapy for human immature and mature permanent teeth with necrotic pulps and/or apical periodontitis, teeth with persistent apical periodontitis after root canal therapy, traumatized teeth with external inflammatory root resorption, and avulsed teeth in terms of elimination of clinical symptoms and resolution of apical periodontitis.

The Use of Mathematical Modelling for Improving the Tissue Engineering of Organs and Stem Cell Therapy.

PubMed

Lemon, Greg; Sjoqvist, Sebastian; Lim, Mei Ling; Feliu, Neus; Firsova, Alexandra B; Amin, Risul; Gustafsson, Ylva; Stuewer, Annika; Gubareva, Elena; Haag, Johannes; Jungebluth, Philipp; Macchiarini, Paolo

2016-01-01

Regenerative medicine is a multidisciplinary field where continued progress relies on the incorporation of a diverse set of technologies from a wide range of disciplines within medicine, science and engineering. This review describes how one such technique, mathematical modelling, can be utilised to improve the tissue engineering of organs and stem cell therapy. Several case studies, taken from research carried out by our group, ACTREM, demonstrate the utility of mechanistic mathematical models to help aid the design and optimisation of protocols in regenerative medicine.

Electrotherapy and hyperbaric oxygen: Promising treatments for postradiation complications

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.E.; Scheetz, J.; Jacob, R.F.

1989-09-01

Electrotherapy and hyperbaric oxygen therapy have been added to physical therapy to treat patients with postsurgery and radiation sequelae. Problems of reduced oral opening and range of head movement, soft tissue necrosis, osteoradionecrosis, and delayed wound healing were addressed in 37 patients over a 3-year period. Of this group, 16 irradiated maxillary resection patients were specifically followed up to determine the effectiveness of the new modalities on improving reduced oral opening. Although healing and the quality of the soft tissues showed marked improvement there was no significant improvement in oral opening.

Metalloporphyrins and their uses as imageable tumor-targeting agents for radiation therapy

DOEpatents

Miura, Michiko; Slatkin, Daniel N.

2003-05-20

The present invention covers halogenated derivatives of boronated porphyrins containing multiple carborane cages having the formula ##STR1## which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies including, but not limited to, boron neutron- capture therapy and photodynamic therapy. The present invention also covers methods for using these halogenated derivatives of boronated porphyrins in tumor imaging and cancer treatment.

Use of novel metalloporphyrins as imageable tumor-targeting agents for radiation therapy

DOEpatents

Miura, Michiko; Slatkin, Daniel N.

2005-10-04

The present invention covers halogenated derivatives of boronated phorphyrins containing multiple carborane cages having the formula ##STR1## which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies including, but not limited to, boron neutron-capture therapy and photodynamic therapy. The present invention also covers methods for using these halogenated derivatives of boronated porphyrins in tumor imaging and cancer treatment.

The concept and evolution of involved site radiation therapy for lymphoma.

PubMed

Specht, Lena; Yahalom, Joachim

2015-10-01

We describe the development of radiation therapy for lymphoma from extended field radiotherapy of the past to modern conformal treatment with involved site radiation therapy based on advanced imaging, three-dimensional treatment planning and advanced treatment delivery techniques. Today, radiation therapy is part of the multimodality treatment of lymphoma, and the irradiated tissue volume is much smaller than before, leading to highly significant reductions in the risks of long-term complications.

Systemic Gene Therapy for Tuberous Sclerosis

DTIC Science & Technology

2017-07-01

especially for children and LAM patients. Our group is focused on developing gene therapy for TSC which has the potential for single application and low-to...neurologic diseases in adults and children , and AAV9 can deliver genes not only to peripheral tissues, but also to the brain in mice and non-human...therapies, especially for children and LAM patients. Our group is focused on developing gene therapy for TSC which has the potential for single

[The protective effect of bone marrow mesenchymal stem cells carrying antioxidant gene superoxide dismutase on paraquat lung injury in mice].

PubMed

Liu, Hong; Ding, Yingwei; Hou, Yuehui; Zhao, Guangju; Lu, Yang; Chen, Xiao; Cai, Qiqi; Hong, Guangliang; Qiu, Qiaomeng; Lu, Zhongqiu

2016-01-01

To explore the possible mechanism and protective effect of BMSCs (bone mesenchymal stem cells) carrying superoxide dismutase (SOD) gene on mice with paraquat-induced acute lung injury. To establish the cell line of BMSCs bringing SOD gene, lentiviral vector bringing SOD gene was built and co-cultured with BMSCs. A total of 100 BALB/c mice were randomly divided into five groups, namely Control group, poisoning group (PQ group) , BMSCs therapy group (BMSC group) , BMSCs-Cherry therapy group (BMSC-Cherry group) , BMSCs-SOD therapy group (BMSC-SOD group) . PQ poisoning model was produced by stomach lavaged once with 1 ml of 25 mg/kg PQ solution, and the equal volume of normal saline (NS) was given to Control group mice instead of PQ. The corresponding BMSCs therapy cell lines were delivered to mice through the tail vein of mice 4h after PQ treatment.Five mice of each group were sacrificed 3 d, 7 d, 14 d and 21 days after corresponding BMSCs therapy cell lines administration, and lung tissues of mice were taken to make sections for histological analysis. The serum levels of glutathione (GSH) , malondialdehyde (MDA) , SOD, and the levels of transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) in lung tissue were determined. The level of SOD was assayed by Westen-blot. Compared with Control group, the early (3 days) levels of SOD protein in lung tissue of PQ group obviously decreased, and the late (21 days) levels of SOD obviously increased, while in therapy groups, that was higher than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Compared with Control group, the levels of plasma GSH and SOD of PQ group and each therapy group wae significantly lower than those in Control group, while in therapy groups, those were higher than those of PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) .Compared with Control group, the level of plasma MDA, TNF-α and TGF-β in PQ group and therapy groups were significantly higher, while in therapy groups, that was lower than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Lung biopsy showed that, the degree of lung tissue damage in each therapy group obviously reduced. SOD is the key factor of the removal of reactive oxygen species (ROS) in cells, that can obviously inhibit the oxidative stress damage and the apoptosis induced by PQ, thus significantly increasing alveolar epithelial cell ability to fight outside harmful environment.

Complementary Effects of Negative-Pressure Wound Therapy and Pulsed Radiofrequency Energy on Cutaneous Wound Healing in Diabetic Mice.

PubMed

Chen, Bin; Kao, Huang-Kai; Dong, Ziqing; Jiang, Zhaohua; Guo, Lifei

2017-01-01

Negative-pressure wound therapy and pulsed radiofrequency energy are two clinical modalities used to treat soft-tissue wounds. They are purported to affect healing differently. The aim of this experimental study was to contrast the two modalities at a mechanistic level and to investigate whether their combined therapy could achieve additive and complementary effects on wound healing. Full-thickness dorsal cutaneous wounds of diabetic, db/db, mice were treated with either negative-pressure wound therapy, pulsed radiofrequency energy, or combined therapies. Macroscopic healing kinetics were examined. Epidermal regeneration (proliferation rate and length of reepithelialization) and neovascularization (blood vessel density) were investigated. Messenger RNA levels indicative of angiogenic (basic fibroblast growth factor), profibrotic (transforming growth factor-β), epidermal proliferative (keratinocyte growth factor), and extracellular matrix remodeling (collagen 1) processes were measured in wound tissues. All three treatment groups displayed faster wound healing. The negative-pressure wound therapy/pulsed radiofrequency energy combined therapy led to significantly faster healing than either the negative-pressure wound therapy or pulsed radiofrequency energy therapy alone. Epidermal regeneration and neovascularization were enhanced in all three groups. The two negative-pressure wound therapy groups (alone and combined with pulsed radiofrequency energy) demonstrated more significant increases in expression of all assayed growth factors than the pulsed radiofrequency energy group. Furthermore, the combined therapy exhibited a more profound elevation in collagen 1 expression than either of the two therapies alone. Combining the negative-pressure wound therapy and pulsed radiofrequency energy modalities can achieve additive benefits in cutaneous healing, and the two therapies can be easily used together to complement each other in clinical wound treatments.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

PubMed

Xie, Qiang; Wu, Hai-Bing; Yan, Yu-Feng; Liu, Meng; Wang, Er-Song

2017-04-01

The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of vasopressin and terlipressin in refractory shock compared to conventional therapy in the neonatal and pediatric population: a systematic review, meta-analysis, and trial sequential analysis.

PubMed

Masarwa, Reem; Paret, Gideon; Perlman, Amichai; Reif, Shimon; Raccah, Bruria Hirsh; Matok, Ilan

2017-01-05

Vasopressin (AVP) and terlipressin (TP) have been used as last-line therapy in refractory shock in children. However, the efficacy and safety profiles of AVP and TP have not been determined in pediatric refractory shock of different origins. We aimed to assess the efficacy and safety of the addition of AVP/TP therapy in pediatric refractory shock of all causes compared to conventional therapy with fluid resuscitation and vasopressor and inotropic therapy. We conducted a systematic review, meta-analysis, and trial sequential analysis (TSA) comparing AVP and TP to conventional therapy. MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched up to February 2016. The systematic review included all reports of AVP/TP use in the pediatric population. Reports of clinical trials were pooled using random-effects models and TSA. Main outcomes were mortality and tissue ischemia. Three randomized controlled trials and five "before-and-after clinical" trials (without comparator) met the inclusion criteria. Among 224 neonates and children (aged 0 to 18 years) with refractory shock, 152 received therapy with AVP or TP. Pooled analyses showed no association between AVP/TP treatment and mortality (relative risk (RR),1.19; 95% confidence interval (CI), 0.71-2.00), length of stay in the pediatric intensive care unit (PICU) (mean difference (MD), -3.58 days; 95% CI, -9.05 to 1.83), and tissue ischemia (RR, 1.48; 95% CI, 0.47-4.62). In TSA, no significant effect on mortality and risk for developing tissue ischemia was observed with AVP/TP therapy. Our results emphasize the lack of observed benefit for AVP/TP in terms of mortality and length of stay in the PICU, and suggest an increased risk for ischemic events. Our TSA suggests that further large studies are necessary to demonstrate and establish benefits of AVP/TP in children. PROSPERO registry: CRD42016035872.

Male fertility preservation before gonadotoxic therapies

PubMed Central

Wyns, C.

2010-01-01

Background: Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, radiotherapy and preparative regimens for bone marrow transplantation can severely affect male germ cells, including spermatogonial stem cells (SSCs), and lead to permanent loss of fertility. Different options for fertility preservation are dependent on the pubertal state of the patient. Methods: Relevant studies were identified by an extensive Medline search of English and French language articles. Results: Sperm cryopreservation prior to gonadotoxic treatment is a well established method after puberty. In case of ejaculation failure by masturbation, assisted ejaculation methods or testicular tissue sampling should be considered. Although no effective gonadoprotective drug is yet available for in vivo spermatogonial stem cell (SSC) protection in humans, current evidence supports the feasibility of immature testicular tissue (ITT) cryopreservation. The different cryopreservation protocols and available fertility restoration options from frozen tissue, i.e. cell suspension transplantation, tissue grafting and in vitro maturation, are presented. Results obtained in humans are discussed in the light of lessons learned from animal studies. Conclusion: Advances in reproductive technology have made fertility preservation a real possibility in young patients whose gonadal function is threatened by gonadotoxic therapies. The putative indications for such techniques, as well as their limitations according to disease, are outlined. PMID:25302103

Male fertility preservation before gonadotoxic therapies.

PubMed

Wyns, C

2010-01-01

Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, radiotherapy and preparative regimens for bone marrow transplantation can severely affect male germ cells, including spermatogonial stem cells (SSCs), and lead to permanent loss of fertility. Different options for fertility preservation are dependent on the pubertal state of the patient. Relevant studies were identified by an extensive Medline search of English and French language articles. Sperm cryopreservation prior to gonadotoxic treatment is a well established method after puberty. In case of ejaculation failure by masturbation, assisted ejaculation methods or testicular tissue sampling should be considered. Although no effective gonadoprotective drug is yet available for in vivo spermatogonial stem cell (SSC) protection in humans, current evidence supports the feasibility of immature testicular tissue (ITT) cryopreservation. The different cryopreservation protocols and available fertility restoration options from frozen tissue, i.e. cell suspension transplantation, tissue grafting and in vitro maturation, are presented. RESULTS obtained in humans are discussed in the light of lessons learned from animal studies. Advances in reproductive technology have made fertility preservation a real possibility in young patients whose gonadal function is threatened by gonadotoxic therapies. The putative indications for such techniques, as well as their limitations according to disease, are outlined.

Tissue characterization of brain tumors during and after pion radiation therapy.

PubMed

Boesiger, P; Greiner, R; Schoepflin, R E; Kann, R; Kuenzi, U

1990-01-01

Negative Pi-mesons (pions) are applied at the Paul Scherrer Institute in the radiotherapy of highly malignant gliomas using a dose escalation program. The therapy effects of 7 randomly selected patients were followed up by 62 MRI examinations. The quantification of the effects is based on the relaxation times T1 and T2, which are acquired by a new designed multi-echo multiple saturation recovery imaging technique. As a summary of the results, roughly two reaction types are observed. For both types the relaxation times increase up to two to three months after the radiation therapy. Then in one type (two patients) the T1 and T2 values of the tumors, and of the edemas surrounding the tumors, further increase, indicating an unfavorable prognosis. In the other type (five patients) the relaxation times drop down towards, or even below, their initial values, reflecting the onset of the reparation processes in the tissue. This later behaviour reflects an at least temporary control of the disease; that is, the short term prognosis for these patients is more favorable. It further can be concluded, with respect to our MR parameters, that the radiotolerance of healthy brain tissue is much higher than that of malignant glioma tissue, despite the fact that these tumors are very seldom definitively radiosensible.

Photodynamic diagnosis and related optical techniques for the management of malignant glioma

NASA Astrophysics Data System (ADS)

Sroka, R.; Stepp, H.; Beyer, W.; Markwardt, N.; Rühm, A.

2017-04-01

Malignant gliomas are a devastating brain tumor disease with very poor prognosis. Stereotactic biopsy sampling is routinely used in larger neurosurgical centers to confirm the diagnosis of a suspected brain tumor. This procedure is associated with risk of blood vessel rupture as well as false-negative results. Recent investigations suggest a potential of light-based techniques to improve both therapy and diagnosis of GBM. Optical guidance can be utilized to improve the biopsy sampling procedure in terms of safety, reliability, and efficacy. Recording of optical signals (transmission, remission, fluorescence) can be potentially integrated into a biopsy needle for providing optical detection of tumor tissue and blood vessel recognition during the biopsy sampling. Optical signals can also be used for monitoring purposes during photodynamic therapy. Here, fluorescence signals recorded before the treatment indicate the presence and accumulation level of photosensitizer, while photobleaching of the photosensitizer fluorescence during the treatment can be used as a measure of the effectiveness of the therapy. Finally, transmitted light can reveal problematic tissue-optical conditions as well as changes of the optical properties of the treated tissue, which may be relevant with regard to treatment prognosis and strategy. Different optical concepts for interstitial PDT monitoring and optical tissue property assessment are presented.

Engineering a clinically-useful matrix for cell therapy.

PubMed

Prestwich, Glenn D

2008-01-01

The design criteria for matrices for encapsulation of cells for cell therapy include chemical, biological, engineering, marketing, regulatory, and financial constraints. What is required is a biocompatible material for culture of cells in three-dimensions (3-D) that offers ease of use, experimental flexibility to alter composition and compliance, and a composition that would permit a seamless transition from in vitro to in vivo use. The challenge is to replicate the complexity of the native extracellular matrix (ECM) environment with the minimum number of components necessary to allow cells to rebuild a given tissue. Our approach is to deconstruct the ECM to a few modular components that can be reassembled into biomimetic materials that meet these criteria. These semi-synthetic ECMs (sECMs) employ thiol-modified derivatives of hyaluronic acid (HA) that can form covalently crosslinked, biodegradable hydrogels. These sECMs are "living" biopolymers, meaning that they can be crosslinked in the presence of cells or tissues to enable cell therapy and tissue engineering. Moreover, the sECMs allow inclusion of the appropriate biological cues needed to simulate the complexity of the ECM of a given tissue. Taken together, the sECM technology offers a manufacturable, highly reproducible, flexible, FDA-approvable, and affordable vehicle for cell expansion and differentiation in 3-D.

Placental-derived stem cells: Culture, differentiation and challenges

PubMed Central

Oliveira, Maira S; Barreto-Filho, João B

2015-01-01

Stem cell therapy is a promising approach to clinical healing in several diseases. A great variety of tissues (bone marrow, adipose tissue, and placenta) are potentially sources of stem cells. Placenta-derived stem cells (p-SCs) are in between embryonic and mesenchymal stem cells, sharing characteristics with both, such as non-carcinogenic status and property to differentiate in all embryonic germ layers. Moreover, their use is not ethically restricted as fetal membranes are considered medical waste after birth. In this context, the present review will be focused on the biological properties, culture and potential cell therapy uses of placental-derived stem cells. Immunophenotype characterization, mainly for surface marker expression, and basic principles of p-SC isolation and culture (mechanical separation or enzymatic digestion of the tissues, the most used culture media, cell plating conditions) will be presented. In addition, some preclinical studies that were performed in different medical areas will be cited, focusing on neurological, liver, pancreatic, heart, muscle, pulmonary, and bone diseases and also in tissue engineering field. Finally, some challenges for stem cell therapy applications will be highlighted. The understanding of the mechanisms involved in the p-SCs differentiation and the achievement of pure cell populations (after differentiation) are key points that must be clarified before bringing the preclinical studies, performed at the bench, to the medical practice. PMID:26029347

Numerical simulation of time fractional dual-phase-lag model of heat transfer within skin tissue during thermal therapy.

PubMed

Kumar, Dinesh; Rai, K N

2017-07-01

In this paper, we investigated the thermal behavior in living biological tissues using time fractional dual-phase-lag bioheat transfer (DPLBHT) model subjected to Dirichelt boundary condition in presence of metabolic and electromagnetic heat sources during thermal therapy. We solved this bioheat transfer model using finite element Legendre wavelet Galerkin method (FELWGM) with help of block pulse function in sense of Caputo fractional order derivative. We compared the obtained results from FELWGM and exact method in a specific case, and found a high accuracy. Results are interpreted in the form of standard and anomalous cases for taking different order of time fractional DPLBHT model. The time to achieve hyperthermia position is discussed in both cases as standard and time fractional order derivative. The success of thermal therapy in the treatment of metastatic cancerous cell depends on time fractional order derivative to precise prediction and control of temperature. The effect of variability of parameters such as time fractional derivative, lagging times, blood perfusion coefficient, metabolic heat source and transmitted power on dimensionless temperature distribution in skin tissue is discussed in detail. The physiological parameters has been estimated, corresponding to the value of fractional order derivative for hyperthermia treatment therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Manual therapy as an effective treatment for fibrosis in a rat model of upper extremity overuse injury

PubMed Central

Bove, Geoffrey M.; Harris, Michele Y; Zhao, Huaqing; Barbe, Mary F.

2016-01-01

Key clinical features of carpal tunnel syndrome and other types of cumulative trauma disorders of the hand and wrist include pain and functional disabilities. Mechanistic details remain under investigation but may involve tissue inflammation and/or fibrosis. We examined the effectiveness of modeled manual therapy (MMT) as a treatment for sensorimotor behavior declines and increased fibrogenic processes occurring in forearm tissues of rats performing an high repetition high force (HRHF) reaching and grasping task for 12 weeks. Young adult, female rats were examined: food restricted control rats (FRC, n=12); rats that were trained for 6 weeks before performing the HRHF task for 12 weeks with no treatment (HRHF-CON, n=11); and HRHF task rats received modeled manual therapy (HRHF-MMT, n=5) for 5 days/week for the duration of the 12-week of task. Rats receiving the MMT expressed fewer discomfort-related behaviors, and performed progressively better in the HRHF task. Grip strength, while decreased after training, improved following MMT. Fibrotic nerve and connective tissue changes (increased collagen and TGF-β1 deposition) present in 12-week HRHF-CON rats were significantly decreased in 12-week HRHF-MMT rats. These observations support the investigation of manual therapy as a preventative for repetitive motion disorders. PMID:26810536

HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honeycutt, Jenna B.; Thayer, William O.; Baker, Caroline E.

Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA andmore » DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (~33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. Furthermore, these observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.« less

HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy

DOE PAGES

Honeycutt, Jenna B.; Thayer, William O.; Baker, Caroline E.; ...

2017-04-17

Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA andmore » DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (~33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. Furthermore, these observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.« less

HIV persistence in tissue macrophages of humanized myeloid only mice during antiretroviral therapy

PubMed Central

Honeycutt, J. B.; Thayer, W.O.; Baker, C. E.; Ribeiro, R.M.; Lada, S.M.; Cao, Y.; Cleary, R. A.; Hudgens, M. G.; Richman, D.D.; Garcia, J. V.

2017-01-01

Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in the host and is never eradicated. One major barrier to eradication is that multiple different cell types are infected that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV disease (1–3); however, their specific role in HIV persistence during long-term suppressive ART has not been established (4–6). Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as determined by a rapid drop in plasma viral load and a dramatic drop in the levels of cell-associated viral RNA and DNA. No virus rebound was observed in the plasma of 67% of the ART treated animals at seven weeks post-ART interruption, and no replication competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (~33%), a significantly delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence of HIV persistence in tissue macrophages in vivo. PMID:28414330

Predictive analysis of photodynamic therapy applied to esophagus cancer

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; del Campo-Gutiérrez, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

2008-04-01

The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

NASA Astrophysics Data System (ADS)

Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

2009-03-01

Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

The case for particle therapy.

PubMed

Jones, B

2006-01-01

Among the most important decisions facing the British Government regarding the treatment of cancer in the National Health Service (NHS) is the purchase of charged particle therapy (CPT) centres. CPT is different from conventional radiotherapy: the dose is deposited far more selectively in Bragg Peaks by either protons or "heavy" ions, such as carbon. In this way, it is possible to "dose paint" targets, voxel by voxel, with far less dose to surrounding tissues than with X-ray techniques. At present the UK possesses a 62 MeV cyclotron proton facility at Clatterbridge (Wirral), which provides therapy for intraocular cancers such as melanoma; for deeper situated cancers in the pelvis, chest etc., much higher energies, over 200 MeV are required from a synchrotron facility. There is an impressive expansion in particle beam therapy (PBT) centres worldwide, since they offer good prospects of improved quality of life with enhanced cancer cures in situations where conventional therapy is limited due to radioresistance or by the close proximity of critical normal tissues. There is a threat to UK Oncology, since it is anticipated that several thousand British patients may require referral abroad for therapy; this would severely disrupt their multidisciplinary management and require demanding logistical support.

rAAV Gene Therapy in a Canavan's Disease Mouse Model Reveals Immune Impairments and an Extended Pathology Beyond the Central Nervous System.

PubMed

Ahmed, Seemin Seher; Schattgen, Stefan A; Frakes, Ashley E; Sikoglu, Elif M; Su, Qin; Li, Jia; Hampton, Thomas G; Denninger, Andrew R; Kirschner, Daniel A; Kaspar, Brian; Matalon, Reuben; Gao, Guangping

2016-06-01

Aspartoacylase (AspA) gene mutations cause the pediatric lethal neurodegenerative Canavan disease (CD). There is emerging promise of successful gene therapy for CD using recombinant adeno-associated viruses (rAAVs). Here, we report an intracerebroventricularly delivered AspA gene therapy regime using three serotypes of rAAVs at a 20-fold reduced dose than previously described in AspA(-/-) mice, a bona-fide mouse model of CD. Interestingly, central nervous system (CNS)-restricted therapy prolonged survival over systemic therapy in CD mice but failed to sustain motor functions seen in systemically treated mice. Importantly, we reveal through histological and functional examination of untreated CD mice that AspA deficiency in peripheral tissues causes morphological and functional abnormalities in this heretofore CNS-defined disorder. We demonstrate for the first time that AspA deficiency, possibly through excessive N-acetyl aspartic acid accumulation, elicits both a peripheral and CNS immune response in CD mice. Our data establish a role for peripheral tissues in CD pathology and serve to aid the development of more efficacious and sustained gene therapy for this disease.

Xenogeneic collagen matrix with coronally advanced flap compared to connective tissue with coronally advanced flap for the treatment of dehiscence-type recession defects.

PubMed

McGuire, Michael K; Scheyer, E Todd

2010-08-01

For root coverage therapy, the connective tissue graft (CTG) plus coronally advanced flap (CAF) is considered the gold standard therapy against which alternative therapies are generally compared. When evaluating these therapies, in addition to traditional measures of root coverage, subject-reported, qualitative measures of esthetics, pain, and overall preferences for alternative procedures should also be considered. This study determines if a xenogeneic collagen matrix (CM) with CAF might be as effective as CTG+CAF in the treatment of recession defects. This study was a single-masked, randomized, controlled, split-mouth study of dehiscence-type recession defects in contralateral sites; one defect received CTG+CAF and the other defect received CM+CAF. A total of 25 subjects (8 male, 17 female; mean age: 43.7 +/- 12.2 years) were evaluated at 6 months and 1 year. The primary efficacy endpoint was recession depth at 6 months. Secondary endpoints included traditional periodontal measures, such as width of keratinized tissue and percentage of root coverage. Subject-reported values of pain, discomfort, and esthetic satisfaction were also recorded. At 6 months, recession depth was on average 0.52 mm for test sites and 0.10 mm for control sites. Recession depth change from baseline was statistically significant between test and control, with an average of 2.62 mm gained at test sites and 3.10 mm gained at control sites for a difference of 0.4 mm (P = 0.0062). At 1 year, test percentage of root coverage averaged 88.5%, and controls averaged 99.3% (P = 0.0313). Keratinized tissue width gains were equivalent for both therapies and averaged 1.34 mm for test sites and 1.26 mm for control sites (P = 0.9061). There were no statistically significant differences between subject-reported values for esthetic satisfaction, and subjects' assessments of pain and discomfort were also equivalent. When balanced with subject-reported esthetic values and compared to historical root coverage outcomes reported by other investigators, CM+CAF presents a viable alternative to CTG+CAF, without the morbidity of soft tissue graft harvest.

Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy.

PubMed

Watanabe, Tsubasa; Hattori, Yoshihide; Ohta, Youichiro; Ishimura, Miki; Nakagawa, Yosuke; Sanada, Yu; Tanaka, Hiroki; Fukutani, Satoshi; Masunaga, Shin-Ichiro; Hiraoka, Masahiro; Ono, Koji; Suzuki, Minoru; Kirihata, Mitsunori

2016-11-08

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [ 18 F]-L-FBPA, an 18 F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [ 18 F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [ 19 F]-L-FBPA as alternatives to [ 18 F]-L-FBPA. SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [ 19 F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [ 19 F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. There were no differences between L-BPA and [ 19 F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [ 19 F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to blood ratio of the boron concentrations derived from the values measured by PET on dose calculation.

Hierarchical Design of Tissue Regenerative Constructs.

PubMed

Rose, Jonas C; De Laporte, Laura

2018-03-01

The worldwide shortage of organs fosters significant advancements in regenerative therapies. Tissue engineering and regeneration aim to supply or repair organs or tissues by combining material scaffolds, biochemical signals, and cells. The greatest challenge entails the creation of a suitable implantable or injectable 3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell-induced tissue formation. This review gives an overview of the essential components of tissue regenerating scaffolds, ranging from the molecular to the macroscopic scale in a hierarchical manner. Further, this review elaborates about recent pivotal technologies, such as photopatterning, electrospinning, 3D bioprinting, or the assembly of micrometer-scale building blocks, which enable the incorporation of local heterogeneities, similar to most native extracellular matrices. These methods are applied to mimic a vast number of different tissues, including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the tremendous progress that has been made in the last decade, it remains a hurdle to build biomaterial constructs in vitro or in vivo with a native-like structure and architecture, including spatiotemporal control of biofunctional domains and mechanical properties. New chemistries and assembly methods in water will be crucial to develop therapies that are clinically translatable and can evolve into organized and functional tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening.

PubMed

Lu, Hong Fang; Leong, Meng Fatt; Lim, Tze Chiun; Chua, Ying Ping; Lim, Jia Kai; Du, Chan; Wan, Andrew C A

2017-05-11

Cardiotoxicity is one of the major reasons for clinical drug attrition. In vitro tissue models that can provide efficient and accurate drug toxicity screening are highly desired for preclinical drug development and personalized therapy. Here, we report the fabrication and characterization of a human cardiac tissue model for high throughput drug toxicity studies. Cardiac tissues were fabricated via cellular self-assembly of human transgene-free induced pluripotent stem cells-derived cardiomyocytes in pre-fabricated polydimethylsiloxane molds. The formed tissue constructs expressed cardiomyocyte-specific proteins, exhibited robust production of extracellular matrix components such as laminin, collagen and fibronectin, aligned sarcomeric organization, and stable spontaneous contractions for up to 2 months. Functional characterization revealed that the cardiac cells cultured in 3D tissues exhibited higher contraction speed and rate, and displayed a significantly different drug response compared to cells cultured in age-matched 2D monolayer. A panel of clinically relevant compounds including antibiotic, antidiabetic and anticancer drugs were tested in this study. Compared to conventional viability assays, our functional contractility-based assays were more sensitive in predicting drug-induced cardiotoxic effects, demonstrating good concordance with clinical observations. Thus, our 3D cardiac tissue model shows great potential to be used for early safety evaluation in drug development and drug efficiency testing for personalized therapy.

A Mechatronic System for Quantitative Application and Assessment of Massage-Like Actions in Small Animals

PubMed Central

Wang, Qian; Zeng, Hansong; Best, Thomas M.; Haas, Caroline; Heffner, Ned T.; Agarwal, Sudha; Zhao, Yi

2013-01-01

Massage therapy has a long history and has been widely believed effective in restoring tissue function, relieving pain and stress, and promoting overall well-being. However, the application of massage-like actions and the efficacy of massage are largely based on anecdotal experiences that are difficult to define and measure. This leads to a somewhat limited evidence-based interface of massage therapy with modern medicine. In this study, we introduce a mechatronic device that delivers highly reproducible massage-like mechanical loads to the hind limbs of small animals (rats and rabbits), where various massage-like actions are quantified by the loading parameters (magnitude, frequency and duration) of the compressive and transverse forces on the subject tissues. The effect of massage is measured by the difference in passive viscoelastic properties of the subject tissues before and after mechanical loading, both obtained by the same device. Results show that this device is useful in identifying the loading parameters that are most conducive to a change in tissue mechanical properties, and can determine the range of loading parameters that result in sustained changes in tissue mechanical properties and function. This device presents the first step in our effort for quantifying the application of massage-like actions used clinically and measurement of their efficacy that can readily be combined with various quantitative measures (e.g., active mechanical properties and physiological assays) for determining the therapeutic and mechanistic effects of massage therapies. PMID:23943071

Treatment of Vascular Soft Tissue Sarcomas With Razoxane, Vindesine, and Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rhomberg, Walter; Wink, Anna; Pokrajac, Boris

2009-05-01

Purpose: In previous studies, razoxane and vindesine together with radiotherapy was proved to be effective in soft tissue sarcomas (STS). Because razoxane leads to a redifferentiation of pathological tumor blood vessels, it was of particular interest to study the influence of this drug combination in vascular soft tissue sarcomas. Methods and Materials: This open multicenter Phase II study was performed by the Austrian Society of Radiooncology. Among 13 evaluable patients (10 angiosarcomas and 3 hemangio-pericytomas), 9 had unresectable measurable disease, 3 showed microscopic residuals, and 1 had a resection with clear margins. They received a basic treatment with razoxane andmore » vindesine supported by radiation therapy. Outcome measures were objective response rates, survival time, and the incidence of distant metastases. Results: In nine patients with measurable vascular soft tissue sarcomas (eight angiosarcomas and one hemangiopericytoma), 6 complete remissions, 2 partial remissions, and 1 minor remission were achieved, corresponding to a major response rate of 89%. A maintenance therapy with razoxane and vindesine of 1 year or longer led to a suppression of distant metastases. The median survival time from the start of the treatment is 23+ months (range, 3-120+) for 12 patients with macroscopic and microscopic residual disease. The progression-free survival at 6 months was 75%. The combined treatment was associated with a low general toxicity, but attention must be given to increased normal tissue reactions. Conclusions: This trimodal treatment leads to excellent response rates, and it suppresses distant metastases when given as maintenance therapy.« less

Extracorporeal shock wave therapy (ESWT) for wound healing: technology, mechanisms, and clinical efficacy.

PubMed

Mittermayr, Rainer; Antonic, Vlado; Hartinger, Joachim; Kaufmann, Hanna; Redl, Heinz; Téot, Luc; Stojadinovic, Alexander; Schaden, Wolfgang

2012-01-01

For almost 30 years, extracorporeal shock wave therapy has been clinically implemented as an effective treatment to disintegrate urinary stones. This technology has also emerged as an effective noninvasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life. Intensive wound care is required, and this places an enormous burden on society in terms of lost productivity and healthcare costs. Therefore, cost-effective, noninvasive, and efficacious treatments are imperative to achieve both (accelerated and complete) healing of problematic wounds and reduce treatment-related costs. Several experimental and clinical studies show efficacy for extracorporeal shock wave therapy as means to accelerate tissue repair and regeneration in various wounds. However, the biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains unclear. Potential mechanisms, which are discussed herein, include initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves. This review aims to provide an overview of shock wave therapy, its history and development as well as its current place in clinical practice. Recent research advances are discussed emphasizing the role of extracorporeal shock wave therapy in soft tissue wound healing. © 2012 by the Wound Healing Society.

Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis.

PubMed

Borab, Zachary; Mirmanesh, Michael D; Gantz, Madeleine; Cusano, Alessandro; Pu, Lee L Q

2017-04-01

Every year, 1.2 million cancer patients receive radiation therapy in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. Tissue injury can include skin necrosis, which can lead to chronic nonhealing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Adhering to PRISMA guidelines, a systematic review of currently published articles was performed, evaluating the use of hyperbaric oxygen to treat skin necrosis. Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation-induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes; however, additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation-induced skin necrosis. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Acute effects of low-level laser therapy (660 nm) on oxidative stress levels in diabetic rats with skin wounds.

PubMed

Denadai, Amanda Silveira; Aydos, Ricardo Dutra; Silva, Iandara Schettert; Olmedo, Larissa; de Senna Cardoso, Bruno Mendonça; da Silva, Baldomero Antonio Kato; de Carvalho, Paulo de Tarso Camillo

2017-09-01

Laser therapy influences oxidative stress parameters such as the activity of antioxidant enzymes and the production of reactive oxygen species. To analyze the effects of low-level laser therapy on oxidative stress in diabetics rats with skin wounds. Thirty-six animals were divided into 4 groups: NDNI: non-diabetic rats with cutaneous wounds that not received laser therapy; NDI: non-diabetic rats with cutaneous wounds that received laser therapy; DNI: diabetic rats with skin wounds who did not undergo laser therapy; DI: rats with diabetes insipidus and cutaneous wounds and received laser therapy. The animals were treated with LLLT (660 nm, 100 mW, 6 J/cm, spot size 0.028 cm). On the day of killing the animals, tissue-wrapped cutaneous wounds were collected and immediately frozen, centrifuged, and stored to analyze malondialdehyde (MDA) levels. Significant difference was observed within the groups of MDA levels (ANOVA, p = 0.0001). Tukey's post-hoc test showed significantly lower values of MDA in irradiated tissues, both in diabetic and non-diabetic rats. ANOVA of the diabetic group revealed a significant difference (p &#60; 0.01) when all groups, except NDI and DI, were compared. LLLT was effective in decreasing MDA levels in acute surgical wounds in diabetic rats.

Free radical scavenging injectable hydrogels for regenerative therapy.

PubMed

Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2017-02-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of metallic implants on electroporation therapies: feasibility of irreversible electroporation for brachytherapy salvage.

PubMed

Neal, Robert E; Smith, Ryan L; Kavnoudias, Helen; Rosenfeldt, Franklin; Ou, Ruchong; Mclean, Catriona A; Davalos, Rafael V; Thomson, Kenneth R

2013-12-01

Electroporation-based therapies deliver brief electric pulses into a targeted volume to destabilize cellular membranes. Nonthermal irreversible electroporation (IRE) provides focal ablation with effects dependent on the electric field distribution, which changes in heterogeneous environments. It should be determined if highly conductive metallic implants in targeted regions, such as radiotherapy brachytherapy seeds in prostate tissue, will alter treatment outcomes. Theoretical and experimental models determine the impact of prostate brachytherapy seeds on IRE treatments. This study delivered IRE pulses in nonanimal, as well as in ex vivo and in vivo tissue, with and in the absence of expired radiotherapy seeds. Electrical current was measured and lesion dimensions were examined macroscopically and with magnetic resonance imaging. Finite-element treatment simulations predicted the effects of brachytherapy seeds in the targeted region on electrical current, electric field, and temperature distributions. There was no significant difference in electrical behavior in tissue containing a grid of expired radiotherapy seeds relative to those without seeds for nonanimal, ex vivo, and in vivo experiments (all p > 0.1). Numerical simulations predict no significant alteration of electric field or thermal effects (all p > 0.1). Histology showed cellular necrosis in the region near the electrodes and seeds within the ablation region; however, there were no seeds beyond the ablation margins. This study suggests that electroporation therapies can be implemented in regions containing small metallic implants without significant changes to electrical and thermal effects relative to use in tissue without the implants. This supports the ability to use IRE as a salvage therapy option for brachytherapy.

Image-based modeling of tumor shrinkage in head and neck radiation therapy1

PubMed Central

Chao, Ming; Xie, Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing, Lei

2010-01-01

Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the “ground truth” with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy. PMID:20527569

Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles

PubMed Central

Wen, Liewei; Yang, Sihua; Zhong, Junping; Zhou, Quan; Xing, Da

2017-01-01

Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy. PMID:28638483

Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles.

PubMed

Wen, Liewei; Yang, Sihua; Zhong, Junping; Zhou, Quan; Xing, Da

2017-01-01

Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy.

Blood vessel crosstalk during organogenesis – Focus on Pancreas

PubMed Central

Azizoglu, D. Berfin; Cleaver, Ondine

2016-01-01

Blood vessels form a highly branched, interconnected and largely stereotyped network of tubes that sustains every organ and tissue in vertebrates. How vessels come to take on their particular architecture, or how they are ‘patterned’, and in turn, how they influence surrounding tissues are fundamental questions of organogenesis. Decades of work have begun to elucidate how endothelial progenitors arise and home to precise locations within tissues, integrating attractive and repulsive cues to build vessels where they are needed. Conversely, more recent findings have revealed an exciting facet of blood vessel interaction with tissues, where vascular cells provide signals to developing organs and progenitors therein. Here, we discuss the exchange of reciprocal signals between endothelial cells (ECs) and neighboring tissues during embryogenesis, with a special focus on the developing pancreas. Understanding the mechanisms driving both sides of these interactions will be crucial to the development of therapies, from improving organ regeneration to efficient production of cell based therapies. Specifically, elucidating the interface of the vasculature with pancreatic lineages, including endocrine cells, will instruct approaches such as generation of replacement beta cells for Type I diabetes. PMID:27328421

Stereology techniques in radiation biology

NASA Technical Reports Server (NTRS)

Kubinova, Lucie; Mao, XiaoWen; Janacek, Jiri; Archambeau, John O.; Nelson, G. A. (Principal Investigator)

2003-01-01

Clinicians involved in conventional radiation therapy are very concerned about the dose-response relationships of normal tissues. Before proceeding to new clinical protocols, radiation biologists involved with conformal proton therapy believe it is necessary to quantify the dose response and tolerance of the organs and tissues that will be irradiated. An important focus is on the vasculature. This presentation reviews the methodology and format of using confocal microscopy and stereological methods to quantify tissue parameters, cell number, tissue volume and surface area, and vessel length using the microvasculature as a model tissue. Stereological methods and their concepts are illustrated using an ongoing study of the dose response of the microvessels in proton-irradiated hemibrain. Methods for estimating the volume of the brain and the brain cortex, the total number of endothelial cells in cortical microvessels, the length of cortical microvessels, and the total surface area of cortical microvessel walls are presented step by step in a way understandable for readers with little mathematical background. It is shown that stereological techniques, based on a sound theoretical basis, are powerful and reliable and have been used successfully.

Fourier and non-Fourier bio-heat transfer models to predict ex vivo temperature response to focused ultrasound heating

NASA Astrophysics Data System (ADS)

Li, Chenghai; Miao, Jiaming; Yang, Kexin; Guo, Xiasheng; Tu, Juan; Huang, Pintong; Zhang, Dong

2018-05-01

Although predicting temperature variation is important for designing treatment plans for thermal therapies, research in this area is yet to investigate the applicability of prevalent thermal conduction models, such as the Pennes equation, the thermal wave model of bio-heat transfer, and the dual phase lag (DPL) model. To address this shortcoming, we heated a tissue phantom and ex vivo bovine liver tissues with focused ultrasound (FU), measured the temperature response, and compared the results with those predicted by these models. The findings show that, for a homogeneous-tissue phantom, the initial temperature increase is accurately predicted by the Pennes equation at the onset of FU irradiation, although the prediction deviates from the measured temperature with increasing FU irradiation time. For heterogeneous liver tissues, the predicted response is closer to the measured temperature for the non-Fourier models, especially the DPL model. Furthermore, the DPL model accurately predicts the temperature response in biological tissues because it increases the phase lag, which characterizes microstructural thermal interactions. These findings should help to establish more precise clinical treatment plans for thermal therapies.

Potential feasibility of dental stem cells for regenerative therapies: stem cell transplantation and whole-tooth engineering.

PubMed

Nakahara, Taka

2011-07-01

Multipotent mesenchymal stem cells from bone marrow are expected to be a somatic stem cell source for the development of new cell-based therapy in regenerative medicine. However, dental clinicians are unlikely to carry out autologous cell/tissue collection from patients (i.e., marrow aspiration) as a routine procedure in their clinics; hence, the utilization of bone marrow stem cells seems impractical in the dental field. Dental tissues harvested from extracted human teeth are well known to contain highly proliferative and multipotent stem cell compartments and are considered to be an alternative autologous cell source in cell-based medicine. This article provides a short overview of the ongoing studies for the potential application of dental stem cells and suggests the utilization of 2 concepts in future regenerative medicine: (1) dental stem cell-based therapy for hepatic and other systemic diseases and (2) tooth replacement therapy using the bioengineered human whole tooth, called the "test-tube dental implant." Regenerative therapies will bring new insights and benefits to the fields of clinical medicine and dentistry.

Safety and efficacy of targeted hyperthermia treatment utilizing gold nanorod therapy in spontaneous canine neoplasia.

PubMed

Schuh, Elizabeth M; Portela, Roberta; Gardner, Heather L; Schoen, Christian; London, Cheryl A

2017-10-02

Hyperthermia is an established anti-cancer treatment but is limited by tolerance of adjacent normal tissues. Parenteral administration of gold nanorods (NRs) as a photosensitizer amplifies the effects of hyperthermia treatment while sparing normal tissues. This therapy is well tolerated and has demonstrated anti-tumor effects in mouse models. The purpose of this phase 1 study was to establish the safety and observe the anti-tumor impact of gold NR enhanced (plasmonic) photothermal therapy (PPTT) in client owned canine patients diagnosed with spontaneous neoplasia. Seven dogs underwent gold NR administration and subsequent NIR PPTT. Side effects were mild and limited to local reactions to NIR laser. All of the dogs enrolled in the study experienced stable disease, partial remission or complete remission. The overall response rate (ORR) was 28.6% with partial or complete remission of tumors at study end. PPTT utilizing gold nanorod therapy can be safely administered to canine patients. Further studies are needed to determine the true efficacy in a larger population of canine cancer patients and to and identify those patients most likely to benefit from this therapy.

Photodynamic hyperthermal chemotherapy with indocyanine green: a novel cancer therapy for 16 cases of malignant soft tissue sarcoma

PubMed Central

Onoyama, Masaki; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Minami, Saburo; Azuma, Kazuo; Kawashima, Kazuhiko; Ishi, Hiroshi; Takayama, Takahiro; Ogawa, Nobuhiko

2014-01-01

Sixteen cases of malignant soft tissue sarcoma (STS; 10 canines and six felines) were treated with a novel triple therapy that combined photodynamic therapy, hyperthermia using indocyanine green with a broadband light source, and local chemotherapy after surgical tumor resection. This triple therapy was called photodynamic hyperthermal chemotherapy (PHCT). In all cases, the surgical margin was insufficient. In one feline case, PHCT was performed without surgical resection. PHCT was performed over an interval of 1 to 2 weeks and was repeated three to 21 times. No severe side effects, including severe skin burns, necrosis, or skin suture rupture, were observed in any of the animals. No disease recurrence was observed in seven out of 10 (70.0%) dogs and three out of six (50.0%) cats over the follow-up periods ranging from 238 to 1901 days. These results suggest that PHCT decreases the risk of STS recurrence. PHCT should therefore be considered an adjuvant therapy for treating companion animals with STS in veterinary medicine. PMID:24136207

Imaging Stem Cell Therapy for the Treatment of Peripheral Arterial Disease

PubMed Central

Ransohoff, Julia D.; Wu, Joseph C.

2013-01-01

Arteriosclerotic cardiovascular diseases are among the leading causes of morbidity and mortality worldwide. Therapeutic angiogenesis aims to treat ischemic myocardial and peripheral tissues by delivery of recombinant proteins, genes, or cells to promote neoangiogenesis. Concerns regarding the safety, side effects, and efficacy of protein and gene transfer studies have led to the development of cell-based therapies as alternative approaches to induce vascular regeneration and to improve function of damaged tissue. Cell-based therapies may be improved by the application of imaging technologies that allow investigators to track the location, engraftment, and survival of the administered cell population. The past decade of investigations has produced promising clinical data regarding cell therapy, but design of trials and evaluation of treatments stand to be improved by emerging insight from imaging studies. Here, we provide an overview of pre-clinical and clinical experience using cell-based therapies to promote vascular regeneration in the treatment of peripheral arterial disease. We also review four major imaging modalities and underscore the importance of in vivo analysis of cell fate for a full understanding of functional outcomes. PMID:22239638

Spurious testosterone laboratory results in a patient taking synthetic alkaline phosphatase (asfotase alfa).

PubMed

Sofronescu, Alina G; Ross, Meredith; Rush, Eric; Goldner, Whitney

2018-04-27

We report a case of discordant total and free testosterone values in a patient with hypogonadism and juvenile hypophosphatasia after he initiated treatment with asfotase alfa, recombinant tissue non-specific alkaline phosphatase. Total testosterone was evaluated using immunoassay pre and post initiation of therapy with asfotase alfa, and free testosterone was evaluated using radioimmunoassay and LC-MS/MS while on asfotase alfa therapy. Total testosterone measured by immunoassay was normal prior to therapy with asfotase alfa, and was low post initiation of therapy. During the same time frame, free testosterone measured using RAI and total testosterone measured using LC-MS/MS were normal on asfotase alfa therapy. This suggests assay interference with the total testosterone immunoassay. When laboratory results are discordant or do not match the clinical impression, the possibility of assay interference should be considered. Alternative laboratory methods free of the interference should be selected to evaluate these patients. ALPL gene, Approved name: Alkaline phosphatase, liver/bone/kidney, Synonym: Tissue non-specific alkaline phosphatase (TNSAP). Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Soft Tissue Alterations in Esthetic Postextraction Sites: A 3-Dimensional Analysis.

PubMed

Chappuis, V; Engel, O; Shahim, K; Reyes, M; Katsaros, C; Buser, D

2015-09-01

Dimensional alterations of the facial soft and bone tissues following tooth extraction in the esthetic zone play an essential role to achieve successful outcomes in implant therapy. This prospective study is the first to investigate the interplay between the soft tissue dimensions and the underlying bone anatomy during an 8-wk healing period. The analysis is based on sequential 3-dimensional digital surface model superimpositions of the soft and bone tissues using digital impressions and cone beam computed tomography during an 8-wk healing period. Soft tissue thickness in thin and thick bone phenotypes at extraction was similar, averaging 0.7 mm and 0.8 mm, respectively. Interestingly, thin bone phenotypes revealed a 7-fold increase in soft tissue thickness after an 8-wk healing period, whereas in thick bone phenotypes, the soft tissue dimensions remained unchanged. The observed spontaneous soft tissue thickening in thin bone phenotypes resulted in a vertical soft tissue loss of only 1.6 mm, which concealed the underlying vertical bone resorption of 7.5 mm. Because of spontaneous soft tissue thickening, no significant differences were detected in the total tissue loss between thin and thick bone phenotypes at 2, 4, 6, and 8 wk. More than 51% of these dimensional alterations occurred within 2 wk of healing. Even though the observed spontaneous soft tissue thickening in thin bone phenotypes following tooth extraction conceals the pronounced underlying bone resorption pattern by masking the true bone deficiency, spontaneous soft tissue thickening offers advantages for subsequent bone regeneration and implant therapies in sites with high esthetic demand (Clinicaltrials.gov NCT02403700). © International & American Associations for Dental Research.

A review of research into the uses of low level ultrasound in cancer therapy.

PubMed

Yu, Tinghe; Wang, Zhibiao; Mason, Timothy J

2004-04-01

The use of low power ultrasound in therapeutic medicine is a developing field and this review will concentrate on the applications of this technology in cancer therapy. The effects of low power ultrasound have been evaluated in terms of the biological changes induced in the structure and function of tissue. The main fields of study have been in sonodynamic therapy, improving chemotherapy, gene therapy and apoptosis therapy. The range of ultrasonic power levels that can be effectively employed in therapy appears to be narrow and this may have hindered past research in the applications in cancer treatment.

Current Methods for Skeletal Muscle Tissue Repair and Regeneration

PubMed Central

Liu, Juan; Saul, Dominik; Böker, Kai Oliver; Ernst, Jennifer; Lehman, Wolfgang

2018-01-01

Skeletal muscle has the capacity of regeneration after injury. However, for large volumes of muscle loss, this regeneration needs interventional support. Consequently, muscle injury provides an ongoing reconstructive and regenerative challenge in clinical work. To promote muscle repair and regeneration, different strategies have been developed within the last century and especially during the last few decades, including surgical techniques, physical therapy, biomaterials, and muscular tissue engineering as well as cell therapy. Still, there is a great need to develop new methods and materials, which promote skeletal muscle repair and functional regeneration. In this review, we give a comprehensive overview over the epidemiology of muscle tissue loss, highlight current strategies in clinical treatment, and discuss novel methods for muscle regeneration and challenges for their future clinical translation. PMID:29850487

[Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

NASA Astrophysics Data System (ADS)

Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

2018-02-01

The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

Ischemia-Reperfusion Injury in Stroke

PubMed Central

Nour, May; Scalzo, Fabien; Liebeskind, David S.

2013-01-01

Despite ongoing advances in stroke imaging and treatment, ischemic and hemorrhagic stroke continue to debilitate patients with devastating outcomes at both the personal and societal levels. While the ultimate goal of therapy in ischemic stroke is geared towards restoration of blood flow, even when mitigation of initial tissue hypoxia is successful, exacerbation of tissue injury may occur in the form of cell death, or alternatively, hemorrhagic transformation of reperfused tissue. Animal models have extensively demonstrated the concept of reperfusion injury at the molecular and cellular levels, yet no study has quantified this effect in stroke patients. These preclinical models have also demonstrated the success of a wide array of neuroprotective strategies at lessening the deleterious effects of reperfusion injury. Serial multimodal imaging may provide a framework for developing therapies for reperfusion injury. PMID:25187778

Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

ClinicalTrials.gov

2017-09-07

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Biodegradable nanoparticles for gene therapy technology

NASA Astrophysics Data System (ADS)

Hosseinkhani, Hossein; He, Wen-Jie; Chiang, Chiao-Hsi; Hong, Po-Da; Yu, Dah-Shyong; Domb, Abraham J.; Ou, Keng-Liang

2013-07-01

Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes.

[Advantages and disadvantages of composite tissue allotransplantation].

PubMed

Yang, Yang; Lu, Binglun; Zhang, Hui; Xia, Wei; Yi, Chenggang; Guo, Shuzhong

2009-12-01

To review the research progress of composite tissue allotransplantation (CTA), analyze the superiority and the inferiority, and inform the possible direction of further research. Literature concerning CTA was reviewed and analyzed in terms of the limits of conventional reparative and reconstructive surgery, the definition of CTA, potential advantages, and treatment risks. The clinical research of CTA both at home and abroad proved that the therapeutic effect of CTA was better than that of conventional reparative and reconstructive surgery. However, the risks resulting from immunosuppressive therapy were still the primary factors restraining the wide clinical application of CTA. The development of immunosuppressive therapy explores a great development potential for the CTA, and how to decrease the treatment risk of immunosuppressive therapy will be the main research direction in the field of CTA.

A glycoporphyrin story: from chemistry to PDT treatment of cancer mouse models.

PubMed

Lupu, M; Maillard, Ph; Mispelter, J; Poyer, F; Thomas, C D

2018-06-01

Photodynamic therapy (PDT) represents a non-toxic and non-mutagenic antitumor therapy. The photosensitizer's (PS) chemo-physical properties are essential for the therapy, being responsible for the biological effects induced in the targeted tissues. In this study, we present the synthesis and development of some glycoconjugated porphyrins based on lectin-type receptor interaction. They were tested in vitro for finally choosing the most effective chemical structure for an optimum antitumor outcome. The most effective photosensitizer is substituted by three diethylene glycol α-d-mannosyl groups. In vivo studies allow firstly the determination of some characteristics of the biological processes triggered by the initial photochemical activation. Secondly, they make it possible to improve the therapeutic protocol in the function of the structural architecture of the targeted tumor tissue.

Chondrocyte Differentiation of Human Endometrial Gland-Derived MSCs in Layered Cell Sheets

PubMed Central

Shimizu, Tatsuya; Yamato, Masayuki; Umezawa, Akihiro; Okano, Teruo

2013-01-01

Recently, regenerative medicine using engineered three-dimensional (3D) tissues has been focused. In the fields of cell therapy and regenerative medicine, mesenchymal stem cells (MSCs) are attractive autologous cell sources. While, in bioengineered tissues, a 3D environment may affect the differentiation of the stem cells, little is known regarding the effect of 3D environment on cellular differentiation. In this study, MSC differentiation in in vitro 3D tissue models was assessed by human endometrial gland-derived MSCs (hEMSCs) and cell sheet technology. hEMSC sheets were layered into cell-dense 3D tissues and were cultured on porous membranes. The tissue sections revealed that chondrocyte-like cells were found within the multilayered cell sheets even at 24 h after layering. Immunostainings of chondrospecific markers were positive within those cell sheet constructs. In addition, sulfated glycosaminoglycan accumulation within the tissues increased in proportion to the numbers of layered cell sheets. The findings suggested that a high cell density and hypoxic environment in 3D tissues by layering cell sheets might accelerate a rapid differentiation of hEMSCs into chondrocytes without the help of chondro-differentiation reagents. These tissue models using cell sheets would give new insights to stem cell differentiation in 3D environment and contribute to the future application of stem cells to cartilage regenerative therapy. PMID:24348153

Myocardial Tissue Engineering for Regenerative Applications.

PubMed

Fujita, Buntaro; Zimmermann, Wolfram-Hubertus

2017-09-01

This review provides an overview of the current state of tissue-engineered heart repair with a special focus on the anticipated modes of action of tissue-engineered therapy candidates and particular implications as to transplant immunology. Myocardial tissue engineering technologies have made tremendous advances in recent years. Numerous different strategies are under investigation and have reached different stages on their way to clinical translation. Studies in animal models demonstrated that heart repair requires either remuscularization by delivery of bona fide cardiomyocytes or paracrine support for the activation of endogenous repair mechanisms. Tissue engineering approaches result in enhanced cardiomyocyte retention and sustained remuscularization, but may also be explored for targeted paracrine or mechanical support. Some of the more advanced tissue engineering approaches are already tested clinically; others are at late stages of pre-clinical development. Process optimization towards cGMP compatibility and clinical scalability of contractile engineered human myocardium is an essential step towards clinical translation. Long-term allograft retention can be achieved under immune suppression. HLA matching may be an option to enhance graft retention and reduce the need for comprehensive immune suppression. Tissue-engineered heart repair is entering the clinical stage of the translational pipeline. Like in any effective therapy, side effects must be anticipated and carefully controlled. Allograft implantation under immune suppression is the most likely clinical scenario. Strategies to overcome transplant rejection are evolving and may further boost the clinical acceptance of tissue-engineered heart repair.

Photodynamic therapy: a promising alternative in oncology

NASA Astrophysics Data System (ADS)

Nelius, Thomas; de Riese, Werner T. W.; Filleur, Stephanie

2004-07-01

Photodynamic Therapy (PDT) is a treatment modality that is based on the administration of a photosensitizer and the following application of light in a wavelength range matching the absorption spectrum of the photosensitizer. Ideally the photosensitizer retains in the tumor tissue more than in normal tissue and thus allows targeted destruction of cancerous tissue. The use of PDT is slowly being accepted as a standard treatment for certain types of cancer. This includes mainly treatment strategies with only palliative intentions (obstructive esophageal cancer and advanced lung cancer) while for certain malignant conditions new applications exists that are already intended for cure (e.g. early stage of lung cancer). The main advantage of PDT is that the treatment can be repeated multiple times safely without major side effects. PDT can be safely combined with already established treatment options like surgery, chemotherapy or radiotherapy. A disadvantage of PDT is the only localized effect of the therapy, which usually cannot significantly alter the outcome of a systemic disease. In this paper we review the history of PDT as well as current clinical applications in oncology and future directions.

Radiotherapy in the management of keloids. Clinical experience with electron beam irradiation and comparison with X-ray therapy.

PubMed

Maarouf, Mohammad; Schleicher, Ursula; Schmachtenberg, Axel; Ammon, Jürgen

2002-06-01

Aim of this study was to evaluate the advantages of electron beam irradiation compared to kilovoltage X-ray therapy in the treatment of keloids. Furthermore, the risk of developing malignancy following keloid radiotherapy was assessed. An automatic water phantom was used to evaluate the dose distribution in tissue. Furthermore, a series of measurements was done on the patients using thermoluminescence dosimeters (TLD) to estimate the doses absorbed by the organs at risk. We also report our clinical experience with electron beam radiation of 134 keloids following surgical excision. Electron beam irradiation offers a high control rate (84%) with minimal side effects for keloids. Electron irradiation provides better dose distribution in tissue, and therefore less radiation burden to the organs at risk. After a mean follow-up period of 7.2 years, no severe side effects or malignancies were observed after keloid radiotherapy. Electron radiation therapy is superior to kilovoltage irradiation for treating keloids due to better dose distribution in tissue. In agreement with the literature, no cases of malignancy were observed after keloid irradiation.

Multifunctional gold nanorods for image-guided surgery and photothermal therapy

NASA Astrophysics Data System (ADS)

Barriere, Clement; Qi, Ji; Garcia-Allende, P. Beatriz; Newton, Richard; Elson, Daniel S.

2012-03-01

Nanoparticles are viewed as a promising tool for numerous medical applications, for instance imaging and photothermal therapy (PTT) has been proposed using gold nanorods. We are developing multi-functional gold nanorods (m-GNRs) which have potential for image guided endoscopic surgery of tumour tissue with a modified laparoscope system. A new synthesis method potentially allows any useful acid functionalised molecules to be bonded at the surface. We have created fluorescent m-GNRs which can be used for therapy as they absorb light in the infrared, which may penetrate deep into the tissue and produce localised heating. We have performed a tissue based experiment to demonstrate the feasibility of fluorescence guided PTT using m- GNRs. Ex vivo tests were performed using sheep heart. This measurement, correlated with the fluorescence signal of the m-GNRs measured by the laparoscope allows the clear discrimination of the artery system containing m-GNRs. A laser diode was used to heat the m-GNRs and a thermal camera was able to record the heat distribution. These images were compared to the fluorescence images for validation.

Gene Delivery Strategies to Promote Spinal Cord Repair

PubMed Central

Walthers, Christopher M; Seidlits, Stephanie K

2015-01-01

Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed. PMID:25922572

Stem Cell Applications in Tendon Disorders: A Clinical Perspective

PubMed Central

Young, Mark

2012-01-01

Tendon injuries are a common cause of morbidity and a significant health burden on society. Tendons are structural tissues connecting muscle to bone and are prone to tearing and tendinopathy, an overuse or degenerative condition that is characterized by failed healing and cellular depletion. Current treatments, for tendon tear are conservative, surgical repair or surgical scaffold reconstruction. Tendinopathy is treated by exercises, injection therapies, shock wave treatments or surgical tendon debridement. However, tendons usually heal with fibrosis and scar tissue, which has suboptimal tensile strength and is prone to reinjury, resulting in lifestyle changes with activity restriction. Preclinical studies show that cell therapies have the potential to regenerate rather than repair tendon tissue, a process termed tenogenesis. A number of different cell lines, with varying degrees of differentiation, have being evaluated including stem cells, tendon derived cells and dermal fibroblasts. Even though cellular therapies offer some potential in treating tendon disorders, there have been few published clinical trials to determine the ideal cell source, the number of cells to administer, or the optimal bioscaffold for clinical use. PMID:22448174

Periodontal considerations for esthetics: edentulous ridge augmentation.

PubMed

Rosenberg, E S; Cutler, S A

1993-01-01

Edentulous ridge augmentation is a plastic surgical technique that is performed to improve patient esthetics when unsightly, deformed ridges exist. This article describes the etiology of ridge deformities and the many procedures that can be executed to achieve an esthetic, functional result. Historically, soft-tissue mucogingival techniques were described to augment collapsed ridges. Pedicle grafts, free soft-tissue grafts, and subepithelial connective tissue grafts are predictable forms of therapy. More recently, ridge augmentation techniques were developed that regenerate the lost periodontium. These include allografts, bioglasses, guided tissue regenerative procedures, and tissue expansion.

Skeletal status and soft tissue composition in astronauts. Tissue and fluid changes by radionuclide absorptiometry in vivo

NASA Technical Reports Server (NTRS)

Cameron, J. R.; Mazess, R. B.; Wilson, C. R.

1974-01-01

Research on the measurement of bone mineral content and body composition ranges from isotopic tracer methods and the adoption of clinical standards to osteoporosis therapy and the effects of nutritional factors on bone loss.

Perioperative and maintenance therapy following first-line therapy as paradigms for drug discovery in urothelial carcinoma

PubMed Central

Hoffman-Censits, Jean; Wong, Yu-Ning

2015-01-01

Perioperative chemotherapy given to increase the chance of cure for localized disease, and maintenance therapy for metastatic disease, represent distinct aspects of the urothelial cancer disease treatment spectrum. The ability to access both pre and post chemotherapy tissue in the neoadjuvant setting provides important opportunities for translational research to test novel therapies and identify predictors of response to therapy. The maintenance setting may be more complex and study design and endpoints need to be determined based on the candidate drugs mechanism of action and toxicity. PMID:25987535

Postburn itching, pain, and psychological symptoms are reduced with massage therapy.

PubMed

Field, T; Peck, M; Scd; Hernandez-Reif, M; Krugman, S; Burman, I; Ozment-Schenck, L

2000-01-01

Twenty patients with burn injuries were randomly assigned to a massage therapy or a standard treatment control group during the remodeling phase of wound healing. The massage therapy group received a 30-minute massage with cocoa butter to a closed, moderate-sized scar tissue area twice a week for 5 weeks. The massage therapy group reported reduced itching, pain, and anxiety and improved mood immediately after the first and last therapy sessions, and their ratings on these measures improved from the first day to the last day of the study.

Gene therapy strategies for urological dysfunction.

PubMed

Chancellor, M B; Yoshimura, N; Pruchnic, R; Huard, J

2001-07-01

Novel molecular techniques such as conventional and ex vivo gene therapy, and tissue engineering have only recently been introduced to the field of urology. The lower urinary tract is ideally suited for minimally invasive therapy, and also ex vivo approaches would limit the risk of systemic side effects. Muscle-derived stem cells have been used successfully to treat stress incontinence, and rats with diabetic bladder dysfunction benefited from nerve growth factor (NGF)-based gene therapy. Nitric oxide synthase and capase-7 might provide suitable gene therapy targets for erectile dysfunction and benign prostatic hyperplasia, respectively.

Gold nanoshell thermal confinement of conformal laser thermal therapy in liver metastasis

NASA Astrophysics Data System (ADS)

Elliott, Andrew M.; Wang, James; Shetty, Anil M.; Schwartz, Jon; Hazle, John D.; Stafford, R. Jason

2008-02-01

Cooled fiber tip technology has significantly improved the volume coverage of laser induced thermal therapy (LITT), making LITT an attractive technology for the minimally invasive treatment of cancer. Gold coated nanoshells can be tuned to experience a plasmon resonance at a desired laser frequency, there introduction into the treatment region can greatly amplify the effectiveness of the thermal treatment. The goal is to conformaly heat the target, while sparing surrounding healthy tissue. To this end a treatment option that is self-confining to the target lesion is highly desirable. This can be achieved in the liver by allowing nanoshells to be taken up by the healthy tissue of the liver as part of their natural removal from the blood stream. The lesion is then incased inside the nanoshell laden tissue of the surrounding healthy tissue. When an interstitial laser probe is introduced into the center of the lesion the thermal radiation scatters outward until it interacts with and is absorbed by the nanoshells located around the lesion periphery. As the periphery heats it acts as secondary source of thermal radiation, sending heat back into lesion and giving rise to ablative temperatures within the lesion while sparing the surrounding tissue. In order to better monitor therapy and know when the target volume has been ablated, or exceeded, accurate knowledge is needed of both the spatial distribution of heating and the maximum temperature achieved. Magnetic resonance temperature imaging (MRTI) is capable of monitoring the spatiotemporal distribution of temperature in vivo[1]. Experiments have been performed in vitro using a dog liver containing nanoshells (concentration 860ppm) and a tissue like lesion phantom designed to have the optical properties of liver metastasis [2].

Assessment of cone beam CT registration for prostate radiation therapy: fiducial marker and soft tissue methods.

PubMed

Deegan, Timothy; Owen, Rebecca; Holt, Tanya; Fielding, Andrew; Biggs, Jennifer; Parfitt, Matthew; Coates, Alicia; Roberts, Lisa

2015-02-01

This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM ) and the soft tissue prostate (CBCTST ). Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland-Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean ) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST . Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM ) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM . CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of -4.9 to 2.6, -1.6 to 2.5 and -4.7 to 1.9 mm in the superior-inferior, left-right and anterior-posterior planes, respectively. Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy. © 2014 The Royal Australian and New Zealand College of Radiologists.

Expansion in microcarrier-spinner cultures improves the chondrogenic potential of human early mesenchymal stromal cells.

PubMed

Lin, Youshan Melissa; Lim, Jessica Fang Yan; Lee, Jialing; Choolani, Mahesh; Chan, Jerry Kok Yen; Reuveny, Shaul; Oh, Steve Kah Weng

2016-06-01

Cartilage tissue engineering with human mesenchymal stromal cells (hMSC) is promising for allogeneic cell therapy. To achieve large-scale hMSC propagation, scalable microcarrier-based cultures are preferred over conventional static cultures on tissue culture plastic. Yet it remains unclear how microcarrier cultures affect hMSC chondrogenic potential, and how this potential is distinguished from that of tissue culture plastic. Hence, our study aims to compare the chondrogenic potential of human early MSC (heMSC) between microcarrier-spinner and tissue culture plastic cultures. heMSC expanded on either collagen-coated Cytodex 3 microcarriers in spinner cultures or tissue culture plastic were harvested for chondrogenic pellet differentiation with empirically determined chondrogenic inducer bone morphogenetic protein 2 (BMP2). Pellet diameter, DNA content, glycosaminoglycan (GAG) and collagen II production, histological staining and gene expression of chondrogenic markers including SOX9, S100β, MMP13 and ALPL, were investigated and compared in both conditions. BMP2 was the most effective chondrogenic inducer for heMSC. Chondrogenic pellets generated from microcarrier cultures developed larger pellet diameters, and produced more DNA, GAG and collagen II per pellet with greater GAG/DNA and collagen II/DNA ratios compared with that of tissue culture plastic. Moreover, they induced higher expression of chondrogenic genes (e.g., S100β) but not of hypertrophic genes (e.g., MMP13 and ALPL). A similar trend showing enhanced chondrogenic potential was achieved with another microcarrier type, suggesting that the mechanism is due to the agitated nature of microcarrier cultures. This is the first study demonstrating that scalable microcarrier-spinner cultures enhance the chondrogenic potential of heMSC, supporting their use for large-scale cell expansion in cartilage cell therapy. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Boron Neutron Capture Therapy for HER2+ breast cancers: A feasibility study evaluating BNCT for potential role in breast conservation therapies

NASA Astrophysics Data System (ADS)

Jenkins, Peter Anthony

A novel Boron Neutron Capture Therapy (BNCT) regimen for the treatment of HER2+ breast cancers has been proposed as an alternative to whole breast irradiation for breast conservation therapy patients. The proposed therapy regimen is based on the assumed production of boron delivery agents that would be synthesized from compounds of Trastuzumab (Herceptin ®) and oligomeric phosphate diesters (OPDs). The combination of the anti-HER2 monoclonal antibody and the high boron loading capability of OPDs has led to the assumption that boron could be delivered to the HER2+ cancer cells at Tumor to Healthy Tissue ratios (T:H) of up to 35:1 and boron concentrations above 50 μg/g. This significantly increased boron delivery efficiency has opened new BNCT possibilities. This proof of concept study examined treatment parameters derived as the results in previous efforts in the context of patient-specific geometry and compared calculated dose results to those observed during actual patient therapy. These results were based on dose calculations performed with a set of calculated Kerma coefficients derived from tissues specific to the regions of interest for breast cancer. A comparison was made of the dose to the tumor region, the patient's skin, and the peripheral organs. The results of this study demonstrated that, given the performance of the proposed boron delivery agent, the BNCT treatment regimen is feasible. The feasibility is based on the findings that the equivalent dose could be delivered to the treatment volume with less dose to the skin and peripheral organs. This is anticipated to improve the treatment outcomes by maintaining local control of tumor cells while reducing dose to healthy tissues.

[Surgical Regeneration Therapy Using Myoblast Sheets for Severe Heart Failure].

PubMed

Sawa, Yoshiki

2017-01-01

Heart failure is a life-threatening disorder worldwide, and the current end-stage therapies for severe heart failure are replacement therapies such as ventricular-assist devices and heart transplantation. Although these therapies have been reported to be useful, there are many issues in terms of the durability, complications, limited donors, adverse effect of continuous administration of immunosuppressive agents, and high costs involved. Recently, regenerative therapy based on genetic, cellular, or tissue engineering techniques has gained attention as a new therapy to overcome the challenges encountered in transplantation medicine. We focused on skeletal myoblasts as the source of progenitor cells for autologous cell transplantation and the cell-sheet technique for site-specific implantation. In vitro studies have reported that myoblast sheets secrete cytoprotective and angiogenic cytokines such as hepatocyte growth factor (HGF). Additionally, in vivo studies using large and small animal models of heart failure, we have shown that myoblast sheets could improve diastolic and systolic performance and enhance angiogenesis and antifibrosis as well as the expression of several cytokines including HGF and vascular endothelial growth factor(VEGF) in the tissues at the transplanted site. Based on the results of these studies, we performed clinical trials using autologous myoblast sheets in ischemic cardiomyopathy (ICM) and dilated cardiomyopathy patients. Some patients showed left ventricular reverse remodeling and improved symptoms and exercise tolerance. Recently, multiple medical institutions including our institution successfully conducted an exploratory, uncontrolled, open-label phase II study in subjects with ICM to validate the efficacy and safety of autologous myoblast sheets. Moreover, as a novel cell source for regenerative medicine, our recent studies demonstrated that induced pluripotent stem cell-derived cardiomyocyte sheets showed electrical and microstructural homogeneity with heart tissue in vitro and in vivo, thus establishing proof of concept in small and large animal models of heart failure.

Combined photothermal therapy and magneto-motive ultrasound imaging using multifunctional nanoparticles

NASA Astrophysics Data System (ADS)

Mehrmohammadi, Mohammad; Ma, Li L.; Chen, Yun-Sheng; Qu, Min; Joshi, Pratixa; Chen, Raeanna M.; Johnston, Keith P.; Emelianov, Stanislav

2010-02-01

Photothermal therapy is a laser-based non-invasive technique for cancer treatment. Photothermal therapy can be enhanced by employing metal nanoparticles that absorb the radiant energy from the laser leading to localized thermal damages. Targeting of nanoparticles leads to more efficient uptake and localization of photoabsorbers thus increasing the effectiveness of the treatment. Moreover, efficient targeting can reduce the required dosage of photoabsorbers; thereby reducing the side effects associated with general systematic administration of nanoparticles. Magnetic nanoparticles, due to their small size and response to an external magnetic field gradient have been proposed for targeted drug delivery. In this study, we investigate the applicability of multifunctional nanoparticles (e.g., magneto-plasmonic nanoparticles) and magneto-motive ultrasound imaging for image-guided photothermal therapy. Magneto-motive ultrasound imaging is an ultrasound based imaging technique capable of detecting magnetic nanoparticles indirectly by utilizing a high strength magnetic field to induce motion within the magnetically labeled tissue. The ultrasound imaging is used to detect the internal tissue motion. Due to presence of the magnetic component, the proposed multifunctional nanoparticles along with magneto-motive ultrasound imaging can be used to detect the presence of the photo absorbers. Clearly the higher concentration of magnetic carriers leads to a monotonic increase in magneto-motive ultrasound signal. Thus, magnetomotive ultrasound can determine the presence of the hybrid agents and provide information about their location and concentration. Furthermore, the magneto-motive ultrasound signal can indicate the change in tissue elasticity - a parameter that is expected to change significantly during the photothermal therapy. Therefore, a comprehensive guidance and assessment of the photothermal therapy may be feasible through magneto-motive ultrasound imaging and magnetoplasmonic nanoparticles.

Direct tissue oxygen monitoring by in vivo photoacoustic lifetime imaging (PALI)

NASA Astrophysics Data System (ADS)

Shao, Qi; Morgounova, Ekaterina; Ashkenazi, Shai

2014-03-01

Tissue oxygen plays a critical role in maintaining tissue viability and in various diseases, including response to therapy. Images of oxygen distribution provide the history of tissue hypoxia and evidence of oxygen availability in the circulatory system. Currently available methods of direct measuring or imaging tissue oxygen all have significant limitations. Previously, we have reported a non-invasive in vivo imaging modality based on photoacoustic lifetime. The technique maps the excited triplet state of oxygen-sensitive dye, thus reflects the spatial and temporal distribution of tissue oxygen. We have applied PALI on tumor hypoxia in small animals, and the hypoxic region imaged by PALI is consistent with the site of the tumor imaged by ultrasound. Here, we present two studies of applying PALI to monitor changes of tissue oxygen by modulations. The first study involves an acute ischemia model using a thin thread tied around the hind limb of a normal mouse to reduce the blood flow. PALI images were acquired before, during, and after the restriction. The drop of muscle pO2 and recovery from hypoxia due to reperfusion were observed by PALI tracking the same region. The second study modulates tissue oxygen by controlling the percentage of oxygen the mouse inhales. We demonstrate that PALI is able to reflect the change of oxygen level with respect to both hyperbaric and hypobaric conditions. We expect this technique to be very attractive for a range of clinical applications in which tissue oxygen mapping would improve therapy decision making and treatment planning.

Special cases for proton beam radiotherapy: re-irradiation, lymphoma, and breast cancer.

PubMed

Plastaras, John P; Berman, Abigail T; Freedman, Gary M

2014-12-01

The dose distributions that can be achieved with protons are usually superior to those of conventional photon external-beam radiation. There are special cases where proton therapy may offer a substantial potential benefit compared to photon treatments where toxicity concerns dominate. Re-irradiation may theoretically be made safer with proton therapy due to lower cumulative lifetime doses to sensitive tissues, such as the spinal cord. Proton therapy has been used in a limited number of patients with rectal, pancreatic, esophageal, and lung cancers. Chordomas and soft tissue sarcomas require particularly high radiation doses, posing additional challenges for re-irradiation. Lymphoma is another special case where proton therapy may be advantageous. Late toxicities from even relatively low radiation doses, including cardiac complications and second cancers, are of concern in lymphoma patients with high cure rates and long life expectancies. Proton therapy has begun to be used for consolidation after chemotherapy in patients with Hodgkin and non-Hodgkin lymphoma. Breast cancer is another emerging area of proton therapy development and use. Proton therapy may offer advantages compared to other techniques in the setting of breast boosts, accelerated partial breast irradiation, and post-mastectomy radiotherapy. In these settings, proton therapy may decrease toxicity associated with breast radiotherapy. As techniques are refined in proton therapy, we may be able to improve the therapeutic ratio by maintaining the benefits of radiotherapy while better minimizing the risks. Copyright © 2014 Elsevier Inc. All rights reserved.

Serum proteomic analysis of extracorporeal shock wave therapy-enhanced diabetic wound healing in a streptozotocin-induced diabetes model.

PubMed

Yang, Ming-Yu; Chiang, Yuan-Cheng; Huang, Yu-Ting; Chen, Chien-Chang; Wang, Feng-Sheng; Wang, Ching-Jen; Kuo, Yur-Ren

2014-01-01

Previous studies have demonstrated that extracorporeal shock wave therapy has a significant positive effect on accelerating diabetic wound healing. However, the systemic effect after therapy is still unclear. This study investigated the plasma protein expression in the extracorporeal shock wave therapy group and diabetic controls using proteomic study. A dorsal skin defect (6 × 5 cm) in a streptozotocin-induced diabetic Wistar rat model was used. Diabetic rats receiving either no therapy or extracorporeal shock wave therapy after wounding were analyzed. The spots of interest were subjected to in-gel trypsin digestion and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to elucidate the peptide mass fingerprints. The mass spectrometric characteristics of the identified proteins, including their theoretical isoelectric points, molecular weights, sequence coverage, and Mascot score, were analyzed. Protein expression was validated using immunohistochemical analysis of topical periwounding tissues. The proteomic study revealed that at days 3 and 10 after therapy rats had significantly higher abundance of haptoglobin and significantly lower levels of the vitamin D-binding protein precursor as compared with the diabetic controls. Immunohistochemical staining of topical periwounding tissue also revealed significant upregulation of haptoglobin and downregulation of vitamin D-binding protein expression in the extracorporeal shock wave therapy group, which was consistent with the systemic proteome study. Proteome analyses demonstrated an upregulation of haptoglobin and a downregulation of vitamin D-binding protein in extracorporeal shock wave therapy-enhanced diabetic wound healing.

Introduction to regenerative medicine and tissue engineering.

PubMed

Stoltz, J-F; Decot, V; Huseltein, C; He, X; Zhang, L; Magdalou, J; Li, Y P; Menu, P; Li, N; Wang, Y Y; de Isla, N; Bensoussan, D

2012-01-01

Human tissues don't regenerate spontaneously, explaining why regenerative medicine and cell therapy represent a promising alternative treatment (autologous cells or stem cells of different origins). The principle is simple: cells are collected, expanded and introduced with or without modification into injured tissues or organs. Among middle-term therapeutic applications, cartilage defects, bone repair, cardiac insufficiency, burns, liver or bladder, neurodegenerative disorders could be considered.

Conformal thermal therapy using planar ultrasound transducers and adaptive closed-loop MR temperature control: demonstration in gel phantoms and ex vivo tissues

NASA Astrophysics Data System (ADS)

Tang, K.; Choy, V.; Chopra, R.; Bronskill, M. J.

2007-05-01

MRI-guided transurethral ultrasound therapy offers a minimally invasive approach for the treatment of localized prostate cancer. Integrating a multi-element planar transducer with active MR temperature feedback can enable three-dimensional conformal thermal therapy of a target region within the prostate gland while sparing surrounding normal tissues. Continuous measurement of the temperature distribution in tissue enables dynamic compensation for unknown changes in blood flow and tissue properties during treatment. The main goal of this study was to evaluate the feasibility of using active temperature feedback on a clinical 1.5 T MR imager for conformal thermal therapy. MR thermometry was performed during heating in both gel phantoms and excised tissue with a transurethral heating applicator, and the rotation rate and power were varied based on the thermal measurements. The capability to produce a region of thermal damage that matched a target boundary was evaluated. The influence of a cooling gradient (to simulate cooling of the rectum or urethra) on the desired pattern of thermal damage was also investigated in gel phantoms. Results showed high correlation between the desired target boundary and the 55 °C isotherm generated during heating with an average distance error of 0.9 mm ± 0.4 mm (n = 6) in turkey breasts, 1.4 mm ± 0.6 mm (n = 4) in gel phantoms without rectal cooling and 1.4 mm ± 0.6 mm (n = 3) in gel phantoms with rectal cooling. The results were obtained using a temporal update rate of 5 s, a spatial resolution of 3 × 3 × 10 mm for the control point, and a temperature uncertainty of approximately 1 °C. The performance of the control algorithm under these conditions was comparable to that of simulations conducted previously by our group. Overall, the feasibility of generating targeted regions of thermal damage with a transurethral heating applicator and active MR temperature feedback has been demonstrated experimentally. This method of treatment appears capable of accounting for unpredictable and varying tissue properties during the treatment.

Fibres Optiques En Therapie Laser Au Contact Du Tissu

NASA Astrophysics Data System (ADS)

Lenz, P.; Sabben, G.; Lambert, R.; Berger, F.

1984-03-01

Les fibres en quartz, non protegees par un courant de gaz et placees au contact du tissu, peuvent etre utilisees pratiquement indefiniment grace a un "autonettoyage" et une "regenera-tion". Elles provoquent des lesions tissulaires semblables a celles obtenues avec les fibres conventionnelles.

Adult Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Soft tissue sarcomas (STS) arise in any of the extremities, trunk, retroperitoneum, or head and neck. Treatment is determined by the tumor grade and options include surgery, radiation therapy, and chemotherapy. Get comprehensive information for STS and treatment in this clinician summary.

Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy.

PubMed

Reifschneider, Olga; Schütz, Christian L; Brochhausen, Christoph; Hampel, Gabriele; Ross, Tobias; Sperling, Michael; Karst, Uwe

2015-03-01

An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.

Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

PubMed

Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A

2004-08-27

The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.

Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy

PubMed Central

Oshima, Masamitsu; Inoue, Kaoru; Nakajima, Kei; Tachikawa, Tetsuhiko; Yamazaki, Hiromichi; Isobe, Tomohide; Sugawara, Ayaka; Ogawa, Miho; Tanaka, Chie; Saito, Masahiro; Kasugai, Shohei; Takano-Yamamoto, Teruko; Inoue, Takashi; Tezuka, Katsunari; Kuboki, Takuo; Yamaguchi, Akira; Tsuji, Takashi

2014-01-01

Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy. PMID:25116435

Cell- and Gene-Based Therapeutic Strategies for Periodontal Regenerative Medicine

PubMed Central

Rios, Hector F.; Lin, Zhao; Oh, BiNa; Park, Chan Ho; Giannobile, William V.

2012-01-01

Inflammatory periodontal diseases are a leading cause of tooth loss and are linked to multiple systemic conditions, such as cardiovascular disease and stroke. Reconstruction of the support and function of affected tooth-supporting tissues represents an important therapeutic endpoint for periodontal regenerative medicine. An improved understanding of periodontal biology coupled with current advances in scaffolding matrices has introduced novel treatments that use cell and gene therapy to enhance periodontal tissue reconstruction and its biomechanical integration. Cell and gene delivery technologies have the potential to overcome limitations associated with existing periodontal therapies, and may provide a new direction in sustainable inflammation control and more predictable tissue regeneration of supporting alveolar bone, periodontal ligament, and cementum. This review provides clinicians with the current status of these early-stage and emerging cell- and gene-based therapeutics in periodontal regenerative medicine, and introduces their future application in clinical periodontal treatment. The paper concludes with prospects on the application of cell and gene tissue engineering technologies for reconstructive periodontology. PMID:21284553

[Pathomorphology of regenerative processes in mandibular fracture after sodium succinate treatment and laser magnetotherapy in an experimental setting].

PubMed

Faustov, L A; Nedel'ko, N A; Morozova, M V

2001-01-01

Morphological reactions in tissue adjacent to mandibular angular fracture were studied in guinea pigs treated with sodium succinate and laser magnetotherapy. Due to succinate therapy the exudative component of inflammation was less expressed in comparison with the control, macrophagal reaction and neoangiogenesis were activated, the volume of damaged muscle tissue and the incidence of suppurations decreased. The number of osteoblasts increased and new bone structures acquired a lamellar pattern earlier than in the control. Sodium succinate therapy in combination with laser magnetotherapy had a more pronounced positive effect as regards activation of macrophagal reaction and neoangiogenesis and a decrease in the area of fibrosclerotic changes in the zone of damaged muscles, where newly formed myosymplasts differentiated into myotubes and even in muscle fibers. Suppuration of the wound was prevented. Bone tissue in the fracture zone formed without preliminary formation of cartilaginous tissue, which resulted in more rapid osteogenesis (lamellar bone growth in the fracture zone).

Micro-Raman spectroscopy of tissue samples for oral pathology follow-up monitoring

NASA Astrophysics Data System (ADS)

Delfino, I.; Camerlingo, C.; Zenone, F.; Perna, G.; Capozzi, V.; Cirillo, N.; Gaeta, G. M.; Lepore, M.

2010-04-01

An "in vitro" study of Raman spectra from oral human tissues is reported in order to the develop a diagnostic method suitable for "in vivo" oral pathology follow-up. The investigated pathology is Pemphigus Vulgaris (PV) for which new techniques for guiding and monitoring therapy would be particularly useful. Raman spectra were obtained in the wavenumber regions from 1000 to 1800 cm-1 and 2700 to 3200 cm-1 from tissues from patients at different stages of pathology (active PV, under therapy and in PV remission stage) as confirmed by histopathological and immunofluorescence analysis. Differences in the spectra depending on tissue illness stage arise in 1150-1250 cm-1 (amide III) and 1420-1450 cm-1 (CH3 deformation) regions and around 1650 cm-1 (amide I) and 2930 cm-1 (CH3 symmetric stretch). A wavelet deconvolution procedure was applied to the spectra for better discriminating among the three different stages of illness and a linear regression analysis was used to fully exploit the content of information of Raman spectra.

In vitro and in vivo photothermal cancer therapy using excited gold nanorod surface plasmons

NASA Astrophysics Data System (ADS)

Chen, Cheng-Lung; Liu, Bruce; Ou, Min-Nan; Chang, Fu-Hsiung; Lin, Win-Li; Chia, Chih-Ta; Chen, Yang-Yuan

2013-03-01

The application of heat to eliminate or restrain specific cancer cells is proposed as an encouraging approach in optimizing cancer therapy. This talk presents the in vitro and in vivo photothermal cancer therapy using photo-excited gold nanorods (Au NRs), and studies the impact of thermal heat on the necrosis of tumor tissue. The therapeutic efficacy in vivo was evaluated by analyzing tumor size change, vascular development, and histological images. The safety standard for the therapy process and administration of Au NRs were conducted to exclude side effects arising from the irradiation and materials. It is found that the smaller size of Au NRs exhibits better therapeutic efficacy due to their optical absorption efficiency and space distribution uniformity in the cell. The generation of local heating from excited Au NR surface plasmons is high enough to make the tumor tissue gradually develop to an eschar; resulting in a dramatic size decreases in these treated tumors.

The effects of equine peripheral blood stem cells on cutaneous wound healing: a clinical evaluation in four horses.

PubMed

Spaas, J H; Broeckx, S; Van de Walle, G R; Polettini, M

2013-04-01

Stem-cell therapy represents a promising strategy for the treatment of challenging pathologies, such as large, infected wounds that are unresponsive to conventional therapies. The present study describes the clinical application of peripheral blood stem cells (PBSCs) for the treatment of four adult Warmblood horses with naturally occurring wounds, which were unresponsive to conventional therapies for at least 3 months. A visual assessment was performed, and a number of wound-healing parameters (granulation tissue, crust formation and scar formation) were evaluated. In all cases, tissue overgrowth was visible within 4 weeks after PBSC injection, followed by the formation of crusts and small scars in the centre of the wound, with hair regeneration at the edges. In conclusion, this is the first report of PBSC therapy of skin wounds in horses, and it produced a positive visual and clinical outcome. © The Author(s) CED © 2013 British Association of Dermatologists.

Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

PubMed

Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

2014-03-01

New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were investigated in tumor-bearing mice. The time to maximum accumulation of compound 13 in tumor tissue was one-fourth of that of compound 9, and compound 13 showed rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 13 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 13. Tumor growth was significantly inhibited by PDT using 13. These results suggested that 13 might be a good candidate for both PDT and BNCT of cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adjunctive use of antibiotics in periodontal therapy

PubMed Central

Barca, Ece; Cifcibasi, Emine; Cintan, Serdar

2015-01-01

Periodontal diseases are infectious diseases with a mixed microbial aetiology and marked inflammatory response leading to destruction of underlying tissue. Periodontal therapy aims to eliminate pathogens associated with the disease and attain periodontal health. Periodontitis is generally treated by nonsurgical mechanical debridement and regular periodontal maintenance care. Periodontal surgery may be indicated for some patients to improve access to the root surface; however, mechanical debridement alone may not be helpful in all cases. In such cases, adjunctive systemic antibiotic therapy remains the treatment of choice. It can reach microorganisms at the base of the deep periodontal pockets and furcation areas via serum, and also affects organisms residing within gingival epithelium and connective tissue. This review aims to provide an update on clinical issues regarding when and how to prescribe systemic antibiotics in periodontal therapy. The points discussed are the mode of antibiotic action, susceptible periodontal pathogens, antibiotic dosage, antibiotic use in treatment of periodontal disease, and mechanism of bacterial resistance to each antibiotic. PMID:28955547

Atelocollagen sponge and recombinant basic fibroblast growth factor combination therapy for resistant wounds with deep cavities.

PubMed

Nakanishi, Asako; Hakamada, Arata; Isoda, Ken-ichi; Mizutani, Hitoshi

2005-05-01

Recent advances in bioengineering have introduced materials that enhance wound healing. Even with such new tools, some deep ulcers surrounded by avascular tissues, including bone, tendon, and fascia, are resistant to various therapies and easily form deep cavities with loss of subcutaneous tissue. Atelocollagen sponges have been used as an artificial dermis to cover full-thickness skin defects. Topical recombinant human basic fibroblast growth factor has been introduced as a growth factor to induce fibroblast proliferation in skin ulcers. We applied these materials in combination in two patients with deep resistant wounds: one with a cavity reaching the mediastinum through a divided sternum and one with deep necrotic wounds caused by electric burns. These wounds did not respond to the topical basic fibroblast growth factor alone. In contrast, the combination therapy closed the wounds rapidly without further surgical treatment. This combination therapy is a potent treatment for resistant wounds with deep cavities.

High-intensity laser application in Orthodontics

PubMed Central

Sant’Anna, Eduardo Franzotti; Araújo, Mônica Tirre de Souza; Nojima, Lincoln Issamu; da Cunha, Amanda Carneiro; da Silveira, Bruno Lopes; Marquezan, Mariana

2017-01-01

ABSTRACT Introduction: In dental practice, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) are mainly used for dental surgery and biostimulation therapy. Within the Orthodontic specialty, while LLLT has been widely used to treat pain associated with orthodontic movement, accelerate bone regeneration after rapid maxillary expansion, and enhance orthodontic tooth movement, HILT, in turn, has been seen as an alternative for addressing soft tissue complications associated to orthodontic treatment. Objective: The aim of this study is to discuss HILT applications in orthodontic treatment. Methods: This study describes the use of HILT in surgical treatments such as gingivectomy, ulotomy, ulectomy, fiberotomy, labial and lingual frenectomies, as well as hard tissue and other dental restorative materials applications. Conclusion: Despite the many applications for lasers in Orthodontics, they are still underused by Brazilian practitioners. However, it is quite likely that this demand will increase over the next years - following the trend in the USA, where laser therapies are more widely used. PMID:29364385

[New methods of patient selection for improved anticholinergic therapy].

PubMed

Neuhaus, J; Schwalenberg, T; Schlichting, N; Schulze, M; Horn, L-C; Stolzenburg, J-U

2007-09-01

M3-specific inhibitors are currently preferred for anticholinergic therapy of OAB. However, not all of the patients profit from this regimen. This might reflect a heterogeneity of the patient group. The aim of this work is to define subgroups of patients with specific alterations of receptor expression and to profile the receptor expression individually. These receptor profiles might be used for the development of evidence-based "tailored" therapies. Detrusor probes from bladder carcinoma patients (BCa, n=9 F, n=7 male) and interstitial cystitis patients (IC, n=9 female) were examined using confocal immunofluorescence and PCR. M2, M3, P2X1-3, and H1-3 mRNAs were demonstrated in detrusor tissue. As revealed by immunofluorescence, the M2 receptor expression was significantly higher in female compared to male BCa tissues. In addition, the M2 receptor was further upregulated in IC vs BCa in female detrusor. IC patients showed specific alterations of their receptor profile. Individual receptor profiles might be used to optimize medicinal therapies.

Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy

PubMed Central

Key, Jaehong; Park, Kyeongsoon

2017-01-01

Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies. PMID:28282891

The regeneration of thermal wound on mice skin (Mus Musculus) after Q-Switch Nd: YAG laser irradiation for cancer therapy candidate

NASA Astrophysics Data System (ADS)

Apsari, R.; Nahdliyatun, E.; Winarni, D.

2017-09-01

The aims of this study are to investigate the regeneration of mice skin tissue (Mus Musculus) irradiated by Q-Switch Nd: YAG laser and morphological change due to Q-Switch Nd: YAG laser irradiation compared to conventional heating (hairdryer). The 2-3 month of twenty-seven mice were used for experimental animals. Mice were incised in the dorsum by the damage effect of laser energy dose (therapeutic dose) of 29.5 J/cm2 with 10 seconds of exposure time, 10 Hz of repetition rate, and 100 pulses of the given single pulse energy. The mice skin tissue was injuried by hairdryer to get burned effect. Mice were divided into three groups, Group I (control) were not treated by anything, Group II were treated by Q-Switch Nd: YAG laser irradiation and sacrificed on (0, 1, 3, 5) days, and Group III were treated by hairdryer then sacrificed on (0, 1, 3, 5) days. Pathology examination showed that the energy of 29,5 J/cm2 dose produced the hole effect (ablation) through the hypodermic layer caused by optical breakdown and collagen coagulation. Thus, the 60 °C temperature of burn showed coagulation necrosis because piknosis discovered in the injured area. The regeneration process showed that the mice skin tissue's ability to regenerate was irradiated by fast laser because of the focus of Q-Switch Nd: YAG laser. It was showed by the scab releases on third day and completely reepithelialization formation on the fifth day. The collagen fibers distribution was same as normal skin tissue on day 5 and so did angiogenesis. Therefore, Q-Switch Nd: YAG laser can be applied for problems of dermatology medical therapies, especially melasma, nevus of ota and tatto therapy. For skin cancer therapy application, energy dose of unregenerated skin tissue is chosen because the death expected effect is permanent.

Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration.

PubMed

Kawai, Takamasa; Katagiri, Wataru; Osugi, Masashi; Sugimura, Yukiko; Hibi, Hideharu; Ueda, Minoru

2015-04-01

Periodontal tissue regeneration with the use of mesenchymal stromal cells (MSCs) has been regarded as a future cell-based therapy. However, low survival rates and the potential tumorigenicity of implanted MSCs could undermine the efficacy of cell-based therapy. The use of conditioned media from MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim of this study was to confirm the effect of MSC-CM on periodontal regeneration. MSC-CM were collected during their cultivation. The concentrations of the growth factors in MSC-CM were measured with the use of enzyme-linked immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were quantified by means of real-time reverse transcriptase-polymerase chain reaction analysis. In vivo, periodontal defects were prepared in the rat models and the collagen sponges with MSC-CM were implanted. MSC-CM includes insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1 and hepatocyte growth factor. In vitro, wound-healing and angiogenesis increased significantly in MSC-CM. The levels of expression of osteogenetic- and angiogenic-related genes were significantly upregulated in rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after implantation, immunohistochemical analysis showed several CD31-, CD105-or FLK-1-positive cells occurring frequently. At 4 weeks after implantation, regenerated periodontal tissue was observed in MSC-CM groups. The use of MSC-CM may be an alternative therapy for periodontal tissue regeneration because several cytokines included in MSC-CM will contribute to many processes of complicated periodontal tissue regeneration. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.

PubMed

Raghavan, Raghu; Howell, Roger W; Zalutsky, Michael R

2017-06-01

Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67 Ga, 77 Br, 111 In, 125 I, 123 I, 193m Pt, 195m Pt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

Gene Therapy Targeting Glaucoma: Where Are We?

PubMed Central

Liu, Xuyang; Rasmussen, Carol A.; Gabelt, B’Ann T.; Brandt, Curtis R.; Kaufman, Paul L.

2010-01-01

In a chronic disease such as glaucoma, a therapy that provides a long lasting local effect, with minimal systemic side effects, while circumventing the issue of patient compliance, is very attractive. The field of gene therapy is growing rapidly and ocular applications are expanding. Our understanding of the molecular pathogenesis of glaucoma is leading to greater specificity in ocular tissue targeting. Improvements in gene delivery techniques, refinement of vector construction methods, and development of better animal models combine to bring this potential therapy closer to reality. PMID:19539835

The negative effect of hyperbaric oxygen therapy at the acute phase of electrochemical esophageal burn induced by button battery ingestion.

PubMed

Aydin, Atakan; Aktas, Samil; Hafiz, Gunter; Kabakas, Fatih; Erer, Metin; Bilgic, Bilge

2004-07-01

Ingestion of button battery, if lodges in esophagus, causes mucosal destruction in esophagus and may damage surrounding tissues due to electrochemical reactions which may lead to esophagus perforation, tracheosefageal fistula and other serious problems. We designed an experimental study to test the effect of hyperbaric oxygen therapy on battery induced electrochemical tissue damage in the esophagus of a rabbit model and possible change with duration of contact time. Button batteries were inserted in esophagus of 40 rabbits which were divided into four groups. Groups 1 and 2 had 15 min of duration of contact time of battery in esophagus, while Groups 3 and 4 had 30 min. Groups 1 and 3 had hyperbaric oxygen therapy for 3 days; Groups 2 and 4 did not. At the end of 3rd day all animals were sacrified and samples were taken from the esophagus for determination of malondialdehyde levels and for histopathological examination to compare: mucosal destruction, muscular layer involvement, perforation and tracheal involvement between groups. Malondialdehyde levels, mucosal destruction, muscular layer involvement, perforation and tracheal involvement were significantly higher in groups which had 30 min of contact time compared to groups which had 15 min. The same assessments were significantly higher in Group 1 (15 min of contact time with hyperbaric oxygen therapy) compared to Group 2 (15 min of contact time without hyperbaric oxygen therapy). However, the difference between Group 3 (30 min of contact time with hyperbaric oxygen therapy) and Group 4 (30 min of contact time, no hyperbaric oxygen therapy) was not significant. Our study demonstrated that if contact time is 15 min HBO had an additive adverse effect to electrochemically burned esophagus by increasing free radicals and eventually tissue damage. However, if the contact time is 30 min its adverse effect is shielded by huge electrochemical destruction due to long contact time.

Effective cancer laser-therapy design through the integration of nanotechnology and computational treatment planning models

NASA Astrophysics Data System (ADS)

Fisher, Jessica W.; Rylander, Marissa Nichole

2008-02-01

Laser therapies can provide a minimally invasive treatment alternative to surgical resection of tumors. However, the effectiveness of these therapies is limited due to nonspecific heating of target tissue which often leads to healthy tissue injury and extended treatment durations. These therapies can be further compromised due to heat shock protein (HSP) induction in tumor regions where non-lethal temperature elevation occurs, thereby imparting enhanced tumor cell viability and resistance to subsequent chemotherapy and radiation treatments. Introducing multi-walled nanotubes (MWNT) into target tissue prior to laser irradiation increases heating selectivity permitting more precise thermal energy delivery to the tumor region and enhances thermal deposition thereby increasing tumor injury and reducing HSP expression induction. This study investigated the impact of MWNT inclusion in untreated and laser irradiated monolayer cell culture and cell phantom model. Cell viability remained high for all samples with MWNT inclusion and cells integrated into alginate phantoms, demonstrating the non-toxic nature of both MWNTs and alginate phantom models. Following, laser irradiation samples with MWNT inclusion exhibited dramatic temperature elevations and decreased cell viability compared to samples without MWNT. In the cell monolayer studies, laser irradiation of samples with MWNT inclusion experienced up-regulated HSP27, 70 and 90 expression as compared to laser only or untreated samples due to greater temperature increases albeit below the threshold for cell death. Further tuning of laser parameters will permit effective cell killing and down-regulation of HSP. Due to optimal tuning of laser parameters and inclusion of MWNT in phantom models, extensive temperature elevations and cell death occurred, demonstrating MWNT-mediated laser therapy as a viable therapy option when parameters are optimized. In conclusion, MWNT-mediated laser therapies show great promise for effective tumor destruction, but require determination of appropriate MWNT characteristics and laser parameters for maximum tumor destruction.

78 FR 78370 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... via the antibody binding fragment of the CAR. By engineering a T-cell to express a CAR that is...) developed in tissue that has been propagated by serial transplantation (rather than cell culture), (b... marrow transplantation, stem cell therapy, tissue regeneration) Competitive Advantages: Labeling markers...

Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy.

PubMed

Horton, Jureta W

2003-07-15

Burn trauma produces significant fluid shifts that, in turn, reduce cardiac output and tissue perfusion. Treatment approaches to major burn injury include administration of crystalloid solutions to correct hypovolemia and to restore peripheral perfusion. While this aggressive postburn volume replacement increases oxygen delivery to previously ischemic tissue, this restoration of oxygen delivery is thought to initiate a series of deleterious events that exacerbate ischemia-related tissue injury. While persistent hypoperfusion after burn trauma would produce cell death, volume resuscitation may exacerbate the tissue injury that occurred during low flow state. It is clear that after burn trauma, tissue adenosine triphosphate (ATP) levels gradually fall, and increased adenosine monophosphate (AMP) is converted to hypoxanthine, providing substrate for xanthine oxidase. These complicated reactions produce hydrogen peroxide and superoxide, clearly recognized deleterious free radicals. In addition to xanthine oxidase related free radical generation in burn trauma, adherent-activated neutrophils produce additional free radicals. Enhanced free radical production is paralleled by impaired antioxidant mechanisms; as indicated by burn-related decreases in superoxide dismutase, catalase, glutathione, alpha tocopherol, and ascorbic acid levels. Burn related upregulation of inducible nitric oxide synthase (iNOS) may produce peripheral vasodilatation, upregulate the transcription factor nuclear factor kappa B (NF-kappaB), and promote transcription and translation of numerous inflammatory cytokines. NO may also interact with the superoxide radical to yield peroxynitrite, a highly reactive mediator of tissue injury. Free radical mediated cell injury has been supported by postburn increases in systemic and tissue levels of lipid peroxidation products such as conjugated dienes, thiobarbituric acid reaction products, or malondialdehyde (MDA) levels. Antioxidant therapy in burn therapy (ascorbic acid, glutathione, N-acetyl-L-cysteine, or vitamins A, E, and C alone or in combination) have been shown to reduce burn and burn/sepsis mediated mortality, to attenuate changes in cellular energetics, to protect microvascular circulation, reduce tissue lipid peroxidation, improve cardiac output, and to reduce the volume of required fluid resuscitation. Antioxidant vitamin therapy with fluid resuscitation has also been shown to prevent burn related cardiac NF-kappaB nuclear migration, to inhibit cardiomyocyte secretion of TNF-alpha, IL-1beta, and IL-6, and to improve cardiac contractile function. These data collectively support the hypothesis that cellular oxidative stress is a critical step in burn-mediated injury, and suggest that antioxidant strategies designed to either inhibit free radical formation or to scavage free radicals may provide organ protection in patients with burn injury.

Tissue-Engineering Approaches to Restore Kidney Function.

PubMed

Katari, Ravi; Edgar, Lauren; Wong, Theresa; Boey, Angela; Mancone, Sarah; Igel, Daniel; Callese, Tyler; Voigt, Marcia; Tamburrini, Riccardo; Zambon, Joao Paulo; Perin, Laura; Orlando, Giuseppe

2015-10-01

Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized.

Dental and Nondental Stem Cell Based Regeneration of the Craniofacial Region: A Tissue Based Approach

PubMed Central

Hughes, Declan; Song, Bing

2016-01-01

Craniofacial reconstruction may be a necessary treatment for those who have been affected by trauma, disease, or pathological developmental conditions. The use of stem cell therapy and tissue engineering shows massive potential as a future treatment modality. Currently in the literature, there is a wide variety of published experimental studies utilising the different stem cell types available and the plethora of available scaffold materials. This review investigates different stem cell sources and their unique characteristics to suggest an ideal cell source for regeneration of individual craniofacial tissues. At present, understanding and clinical applications of stem cell therapy remain in their infancy with numerous challenges to overcome. In spite of this, the field displays immense capacity and will no doubt be utilised in future clinical treatments of craniofacial regeneration. PMID:27143979

X-ray energy optimization in minibeam radiation therapy.

PubMed

Prezado, Y; Thengumpallil, S; Renier, M; Bravin, A

2009-11-01

The purpose of this work is to assess which energy in minibeam radiation therapy provides the best compromise between the deposited dose in the tumor and the sparing of the healthy tissues. Monte Carlo simulations (PENELOPE 2006) have been used as a method to calculate the ratio of the peak-to-valley doses (PVDR) in the healthy tissues and in the tumor for different beam energies. The maximization of the ratio of PVDR in the healthy tissues and in the tumor has been used as a criterion. The main result of this work is that, for the parameters being used in preclinical trials (minibeam sizes of 600 microm and 1200 microm center-to-center separation), the optimum beam energy is 375 keV. The conclusion is that this is the energy of minibeams that should be used in the preclinical studies.

Emission of Biophotons and Adjustable Sounds by the Fascial System: Review and Reflections for Manual Therapy.

PubMed

Bordoni, Bruno; Marelli, Fabiola; Morabito, Bruno; Sacconi, Beatrice

2018-01-01

Every body structure is wrapped in connective tissue or fascia, creating a structural continuity that gives form and function to every tissue and organ. The fascial tissue is uniformly distributed throughout the body, enveloping, interacting with and permeating blood vessels, nerves, viscera, meninges, bones and muscles, creating various layers at different depths and forming a tridimensional metabolic and mechanical matrix. This article reviews the literature on the emission of biophotons and adjustable sounds by the fascial system, because these biological changes could be a means of local and systemic cellular communication and become another assessment tool for manual (therapy) practitioners. This is the first article that discusses these topics in a single text, attempting to bring such information into an area of application that is beneficial to osteopaths, chiropractors, and manual therapists.

Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS

PubMed Central

Shao, Jingwei; Kraft, John C; Li, Bowen; Yu, Jesse; Freeling, Jennifer; Koehn, Josefin; Ho, Rodney JY

2016-01-01

Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels. A stable nanodrug combination that transports, delivers and accumulates in lymph nodes is needed to clear HIV in lymphoid tissues. This review discusses limitations of current oral combination antiretroviral therapy and advances in anti-HIV nanoformulations. A ‘systems approach’ has been proposed to overcome these limitations. This concept has been used to develop nanoformulations for overcoming drug insufficiency, extending cell and tissue exposure and clearing virus for treating HIV/AIDS. PMID:26892323

Tissue Damage, Temperature, and pH Induced by Different Electrode Arrays on Potato Pieces (Solanum tuberosum L.).

PubMed

González, Maraelys Morales; Aguilar, Claudia Hernández; Pacheco, Flavio Arturo Domínguez; Cabrales, Luis Enrique Bergues; Reyes, Juan Bory; Nava, Juan José Godina; Ambrosio, Paulo Eduardo; Domiguez, Dany Sanchez; Sierra González, Victoriano Gustavo; Pupo, Ana Elisa Bergues; Ciria, Héctor Manuel Camué; Alemán, Elizabeth Issac; García, Francisco Monier; Rivas, Clara Berenguer; Reina, Evelyn Chacón

2018-01-01

One of the most challenging problems of electrochemical therapy is the design and selection of suitable electrode array for cancer. The aim is to determine how two-dimensional spatial patterns of tissue damage, temperature, and pH induced in pieces of potato ( Solanum tuberosum L., var. Mondial) depend on electrode array with circular, elliptical, parabolic, and hyperbolic shape. The results show the similarity between the shapes of spatial patterns of tissue damage and electric field intensity, which, like temperature and pH take the same shape of electrode array. The adequate selection of suitable electrodes array requires an integrated analysis that involves, in a unified way, relevant information about the electrochemical process, which is essential to perform more efficiently way the therapeutic planning and the personalized therapy for patients with a cancerous tumor.

Emission of Biophotons and Adjustable Sounds by the Fascial System: Review and Reflections for Manual Therapy

PubMed Central

Marelli, Fabiola; Sacconi, Beatrice

2018-01-01

Every body structure is wrapped in connective tissue or fascia, creating a structural continuity that gives form and function to every tissue and organ. The fascial tissue is uniformly distributed throughout the body, enveloping, interacting with and permeating blood vessels, nerves, viscera, meninges, bones and muscles, creating various layers at different depths and forming a tridimensional metabolic and mechanical matrix. This article reviews the literature on the emission of biophotons and adjustable sounds by the fascial system, because these biological changes could be a means of local and systemic cellular communication and become another assessment tool for manual (therapy) practitioners. This is the first article that discusses these topics in a single text, attempting to bring such information into an area of application that is beneficial to osteopaths, chiropractors, and manual therapists. PMID:29405763

Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy.

PubMed

Noujaim, Jonathan; Thway, Khin; Bajwa, Zia; Bajwa, Ayeza; Maki, Robert G; Jones, Robin L; Keller, Charles

2015-01-01

Epithelioid sarcoma (ES) is a soft tissue sarcoma of children and young adults for which the preferred treatment for localized disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.