Nearby Tissues Research Articles

Prototype metal artefact reduction algorithm in flat panel computed tomography - evaluation in patients undergoing transarterial hepatic radioembolisation.

To investigate the effect of an on-site prototype metal artefact reduction (MAR) algorithm in cone-beam CT-catheter-arteriography (CBCT-CA) in patients undergoing transarterial radioembolisation (RE) of hepatic masses. Ethical board approved retrospective study of 29 patients (mean 63.7±13.7 years, 11 female), including 16 patients with arterial metallic coils, undergoing CBCT-CA (8s scan, 200 degrees rotation, 397 projections). Image reconstructions with and without prototype MAR algorithm were evaluated quantitatively (streak-artefact attenuation changes) and qualitatively (visibility of hepatic parenchyma and vessels) in near- (<1cm) and far-field (>3cm) of artefact sources (metallic coils and catheters). Quantitative and qualitative measurements of uncorrected and MAR corrected images and different artefact sources were compared RESULTS: Quantitative evaluation showed significant reduction of near- and far-field streak-artefacts with MAR for both artefact sources (p<0.001), while remaining stable for unaffected organs (all p>0.05). Inhomogeneities of attenuation values were significantly higher for metallic coils compared to catheters (p<0.001) and decreased significantly for both after MAR (p<0.001). Qualitative image scores were significantly improved after MAR (all p<0.003) with by trend higher artefact degrees for metallic coils compared to catheters. In patients undergoing CBCT-CA for transarterial RE, prototype MAR algorithm improves image quality in proximity of metallic coil and catheter artefacts. • Metal objects cause artefacts in cone-beam computed tomography (CBCT) imaging. • These artefacts can be corrected by metal artefact reduction (MAR) algorithms. • Corrected images show significantly better visibility of nearby hepatic vessels and tissue. • Better visibility may facilitate image interpretation, save time and radiation exposure.

Infected Abdominal Aortic Aneurysms Treated with Extra-anatomic Prosthesis Bypass in the Retroperitoneum

Infected abdominal aortic aneurysms (iAAAs) are rare but life-threatening diseases. The purpose of the present study was to report our experience of extra-anatomic prosthesis bypass in the retroperitoneum as a treatment for iAAAs. Data of 8 consecutive patients diagnosed with iAAAs and treated by an extra-anatomic prosthesis bypass in the retroperitoneum were retrospectively collected. Operative details were as follows: one side of the retroperitoneal space was selected to build a track, and a bifurcated expanded polytetrafluoroethylene prosthesis was placed through the track. The proximal end of the prosthesis was sutured with the normal segment of abdominal aorta proximal to the infected aneurysm by end-to-end anostomosis. The 2 distal ends of the prosthesis were, respectively, sutured with the external iliac artery distal to the aneurysm. The anastomoses were then consolidated with the nearby connective tissue. After the closure of the retroperitoneum, the infected aneurysm was incised, and the infected tissue was debrided. Drainage tubes were placed in the aneurysm sac, which was packed with an omentum flap. All patients received perioperative antibiotic therapy for a period of time. All 8 patients were regularly followed up by outpatient observation. Eight patients with iAAAs underwent an extra-anatomic prosthesis bypass in the retroperitoneum and debridement of the infected aneurysm. An emergency operation was performed for 1 patient who underwent concomitant gastrointestinal procedures for aortoduodenal fistula. All 8 patients were definitively diagnosed by one or more sequential computed tomography scans combined with other methods. The blood or tissue cultures of all cases were positive in the perioperative period, with Salmonella (5 cases) being the most common pathogens. Other pathogens included Burkholderia pseudomallei (2 cases) and Escherichia coli (1 case). All patients survived and were discharged in 4-5weeks after their operations. All patients were free from graft infection during the follow-up period. The extra-anatomic prosthesis bypass in the retroperitoneum for treating iAAAs was safe and effective. Our experience with the procedure may provide a new approach for the treatment of this disease.

Up-regulated miR-221 expression as a molecular diagnostic marker in laryngeal squamous cell carcinoma and its correlation with Apaf-1 expression.

Despite the improvement in the diagnosis and the management of laryngeal squamous cell carcinoma (LSCC), many patients with advanced-stage have poor prognosis in the form of recurrence, metastasis or death. So, recognition of new molecular markers would facilitate the development of targeted therapies. To investigate miR-221 expression in LSCC and its possible correlation to apoptotic protease activating factor-1 (Apaf-1). Also, we aimed to investigate the association between miR-221 and Apaf-1 expressions and the clinicopathological features of LSCC. We investigated the expression of miR-221 (by qRT-PCR) and Apaf-1 (by qRT-PCR and immunohistochemistry) in primary LSCC and adjacent normal tissues. We found significant up-regulation of miR-221 and significant down-regulation of Apaf-1 expression in LSCC tissues compared to normal nearby laryngeal tissues. In addition, significant associations between up-regulated miR-221 and down-regulated Apaf-1 expressions and clinical stage and lymph node (LN) metastasis (P< 0.001 for each) were found. Furthermore, there was a negative correlation between miR-221 gene expression and Apaf-1 gene expression (r=-0.73, P< 0.001). miR-221 can be considered as a diagnostic marker in LSCC and Apaf-1 may be considered as a possible target of miR-221.

Abstract 2204: A proteomic landscape of diffuse-type gastric cancer

Abstract Gastric cancer is a heterogeneous disease characterized by poor clinical outcomes and limited targeted treatment options. Among them, diffuse-type gastric cancer (DGC) is the subtype with worst prognosis. Here we describe the first proteomic landscape of DGC. We carried out proteome profiling and targeted exome DNA sequencing of 84 DGC samples. We analyzed the 1,008 (168 x 6) raw files together for uniformed quality control and protein identification with 1% global protein false discovery rate (FDR), which resulted in the identification of 11,340 gene products (GPs). A SAM (significance analysis of microarray) analysis identified 1,641 proteins as differentially expressed between T (tumor) and N (nearby) with statistical significance (FDR q value&amp;lt;0.01 by SAM and differential expression ratio&amp;gt;0.5/ &amp;lt; -0.5), including 1,211 up-regulated and 430 down-regulated GPs. Gene Ontology annotation indicated that tumor proteomes were significantly enriched in cell cycle, DNA replication, checkpoint, E2F, WNT, p53 signaling, epithelial mesenchymal transition (EMT), and inflammation/cytokine-receptor interaction pathways, and the proteomes of the nearby tissues are enriched in metabolism pathways, such as fatty acid metabolism, oxidative phosphorylation, and amino acid metabolism. Notably, many gastric makers (ANXA10, VSIG1, CLDN18, CTSE, TFF2, MUC5AC and MUC6) and signature proteins for stomach functions, including digestion, absorption, secretion, and stomach acid generation (PGC, GIF, GAST, and ATP4A), were lost in tumors. Based on proteome profiling alone, DGC can be subtyped into 3 major classes (PX1-3) that exhibit distinct proteome features and correlate with distinct clinical outcomes (Gehan-Breslow-Wilcoxon P = 0.024). PX1 exhibits proteome stability and the best overall survival; PX2 exhibits dysregulation in DNA replication and cell cycle, and is most sensitive to chemotherapy; PX3 features hyper-activated immune response and is not responsive to chemotherapy. We identified seven-marker proteins that can stratify DGC patients into these three subtypes, opening a door for proteome subtyping in clinical application and intervention. Furthermore, we nominated drug target candidates taking into consideration both the altered DGC proteome and association data with patients’ overall survival. This study revealed the altered signaling pathways in DGC and demonstrated the advantage of proteomic approach in molecular subtyping of cancer. Citation Format: Sai Ge, Xia Xia, Chen Ding, Bei Zhen, Quan Zhou, Jinwen Feng, Jiajia Yuan, Rui Chen, Yumei Li, Zhongqi Ge, Jiafu Ji, Lianhai Zhang, Jiayuan Wang, Zhongwu Li, Yumei Lai, Ying Hu, Yanyan Li, Yilin Li, Jing Gao, Lin Chen, Jianming Xu, Chunchao Zhang, Sung Yun Jung, Mingwei Liu, Lei Song, Wanlin Liu, Gaigai Guo, Tongqing Gong, Yin Huang, Yang Qiu, Tieliu Shi, Weimin Zhu, Yi Wang, Fuchu He, Lin Shen, Jun Qin, CNHPP. A proteomic landscape of diffuse-type gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2204. doi:10.1158/1538-7445.AM2017-2204

Hemipelvectomia total em um gato com osteossarcoma osteoblástico

Background: Osteosarcoma (OSA) is a malignant neoplasm of mesenchymal tissue that exhibits various histological features and a differentiated biological clinical behavior. The combination of clinical, radiological, and histopathological features is important for diagnosis. Surgical treatment of neoplasms with pelvic involvement is a challenge. Primary bone tumors are rare in cats and are mostly reported in older animals. The objective of this paper was to report the case of a feline subjected to total hemipelvectomy as primary treatment of pelvic OSA; the surgical technique and histological analysis of the tumor are described. No signs of recurrence were seen during seven months of follow-up.Case: A 4-year-old female mixed breed cat weighing 3 kg was presented with a one year history of increased volume on the hip joint region. Palpation of the increased volume on the hip showed a firm, adhered, and painful mass. Radiographic examination of the pelvis in the dorso ventral projection exhibited a severe osteoblastic bone reaction on the proximal femur, as well as marked periosteal reaction of the hip joint with involvement of the acetabulum. A ventral approach total hemipelvectomy technique was adopted for excision of the tumor. The animal was placed on a lateral position and a circumferential skin incision was performed on the ipsilateral limb of the affected hemipelvis, on the medial portion of the femur, and was extended cranially up to the thoracolumbar region. The pubic symphysis was exposed with a periosteal elevator and a pubic symphysiotomy was performed on the midline using a Liston bone cutter; next, the sacroiliac junction was resected. No drain was used after surgery, only compressive bandages. The patient was hospitalized for post-operative monitoring which included opioids for pain management and a non-steroidal anti-inflammatory drug and a cephalosporin class antibiotic. The wound was cleaned with saline, rifamycin spray (Rifocina Spray®) was applied, and dressing was changed every 12 h. The excised bone was submitted for pathological analysis. Gross examination revealed a 4.2 cm hardened increase in volume on the area of the femoral head and acetabulum, with irregular surface; cut surface was hard and white with black and red spots. Histology revealed osteoblastic OSA with intense and solid fusiform and stellate cells distributed in a solid pattern with no capsular border, with marked infiltration of the bone tissue, marked osteolysis, moderate proliferation of osteoclasts, and moderate anisocytosis and anisokaryosis.Discussion: Bone tumors in cats are rare and develop spontaneously. They exhibit aggressive behavior and promote local bone destruction. Firm consistency and local swelling usually occur in more advanced cases when there is a delay between the onset of clinical signs and the veterinary consultation. Radiological findings such as bone destruction and bone formation are commonly seen in this type of tumor. Hemipelvectomy is considered an aggressive surgical technique, but necessary in many cases, especially when tumors are located in the pelvis and nearby tissues. In the case presented here, this surgery was the most viable and advised therapeutic option because of tumor location. No incidents (i.e. hemorrhage) occurred during the perioperative period. After surgery, the patient continued to perform all custom functions. The hind limb, which was affected in this case, is commonly reported to be affected in the literature; however, it is unusual to have involvement of both bones (pelvis and femur) since vascularization of these bones are independent. Diagnosis was confirmed by histopathology in which a characteristic malignant mesenchymal tumor of primitive bone cells was present, with production of osteoid of variable shapes and quantity with the presence of osteoclastic giant cells.

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer

Our purpose is to present a novel multisource rotating shield brachytherapy (RSBT) apparatus for the simultaneous precise angular and linear positioning of partially shielded 153Gd brachytherapy sources in interstitial needles for the treatment of locally advanced prostate cancer. It is designed to lower the dose to nearby healthy tissues, the urethra in particular, relative to conventional high-dose-rate brachytherapy techniques. Following needle implantation through the patient template, an angular drive mechanism is docked to the patient template. Each needle is coupled to a multisource afterloader catheter by a connector passing through a shaft. The shafts are rotated about their axes by translating a moving template between 2 stationary templates. The shafts' surfaces and moving template holes are helically threaded with the same pattern such that translation of the moving template causes simultaneous rotation of the shafts. The rotation of each shaft is mechanically transmitted to the catheter-source-shield combination, inside the needles, via several key-keyway pairs. The catheter angles are simultaneously incremented throughout treatment, and only a single 360° rotation of all catheters is needed for a full treatment.For each rotation angle, source depth in each needle is controlled by a multisource afterloader, which is proposed as an array of belt-driven linear actuators, each of which drives a wire that controls catheter depth in a needle. Treatment plans demonstrated that RSBT with the proposed apparatus reduced urethralD0.1cm3 (the minimum dose delivered to the hottest 0.1cm3 of the urethra) below that of conventional high-dose-rate brachytherapy by 31% for urethral dose gradient volume within 3mm of the urethra surface.Treatment time to deliver 20Gy with the proposed multisource RSBT apparatus by use of nineteen 62.4-GBq 153Gd sources was 122minutes. The proposed RSBT delivery apparatus enables a mechanically feasible urethra-sparing treatment technique for prostate cancer in a clinically reasonable time frame.

Effects of nanobubble collapse on cell membrane integrity.

Recent studies have shown that ultrasound is used to open drug-carrying liposomes to release their payloads; however, a shockwave energetic enough to rupture lipid membranes can cause collateral damage to surrounding cells. Similarly, a destructive shockwave, which may be used to rupture a cell membrane in order to lyse the cell (e.g., as in cancer treatments) may also impair or destroy nearby healthy tissue. To address this problem, we use dissipative particle dynamic (DPD) simulation to investigate the addition of a cavitation bubble between the shockwave and the model cell membrane to alter the shockwave front, allowing low-velocity shockwaves to specifically damage an intended target. We focus specifically on a spherical lipid bilayer model, and note the effect of shockwave velocity, bubble size, and orientation on the damage to the model cell. We show that a cavitation bubble greatly decreases the necessary shockwave velocity required to damage the lipid bilayer and rupture the model cell. The cavitation bubble focuses the kinetic energy of the shockwave front into a smaller area, inducing penetration at the edge of the model cell. With this work, we provide a comprehensive approach to the intricacies of model cell destruction via shockwave impact, and hope to offer a guideline for initiating targeted cellular destruction using induced cavitation bubbles and low-velocity shockwaves.

Radiation dose to non-targeted tissues of the eye during polymer-based delivery of 90Y to ocular melanoma of the choroid

Melanoma of the choroid is a rare cancer that is often treated with radiation-source brachytherapy plaques that are surgically placed near the melanoma. As an alternative, a new synthetic radionuclide polymer composite is being developed to deliver and confine a therapeutic radioactive source (yttrium-90-phosphate microspheres) directly within the tumor. The polymer composite is liquid at room temperature but gels at body temperature through formation of polymer cross-links. The resulting solid-phase gel physically traps the radioactive source to prevent redistribution away from the injection site. We performed a computational feasibility study of the radiation dosimetry of Y-90 placed within ocular melanomas of five sizes. Simulated tumors were modeled at five different anatomical regions within a reference eye model. The Monte Carlo radiation transport code MCNPX was used to assess dose coefficients. Dose coefficients were determined for the melanomas and used to assess six non-targeted tissues of the eye: the ciliary body, total lens, sensitive volume of the lens, retina, optic nerve, and the distal tip of the central retinal artery. The dose coefficients were used to determine mean doses received by all non-targeted tissues for a treatment of 85 Gy to the melanoma. Seventeen treatment scenarios resulted in no non-targeted tissues receiving mean doses at or above nominal thresholds for deterministic effects. The eight scenarios that did result in doses above threshold values were for either the largest tumor volumes considered, or tumors located within the posterior region of the eye. Yttrium-90 polymer composites may serve as a potential treatment for tumors of the eye to deliver highly localized therapeutic radiation with substantial sparing of nearby normal tissue. For larger tumors and for those localized in the posterior regions of the eye, Y-90 beta particle cross-dose may result in unacceptable doses leading to radiation complications in neighboring ocular structures.

CT-guided microwave ablation through the lungs for treating liver tumors near the diaphragm.

PurposeTo explore the short-term efficacy and safety of CT-guided microwave ablation (MWA) for treating liver tumors near the diaphragm.ResultsThe complete response (CR) rate for CT-guided MWA through the lung was 94.7% (124/131). The incomplete response (ICR) rate was 5.3% (7/131), of which 6 patients with ICRs achieved CRs after MWA. The CR rate for Group I was higher than Group II (99.0% vs. 80.0%, P=0.001). The mean follow-up time was 11.2 ±7.50 months. The total local recurrence (LR) rate was 15.3% (20/131). The complication rate was 26.5%, and no severe complications were recorded. All complications were controllable and treatable. The incidence of diaphragmatic thickening during the MWA was 18.8% (P>0.05); the incidence of exudative changes inside the lungs was 6.8% (P>0.05).ConclusionsCT-guided MWA can detect changes in liver tissue, in the diaphragm and nearby lung tissues during the ablation process. It’s safe and effective to treat tumors close to the diaphragm by CT-guided MWA through the lung.MethodsCT-guided MWA was used on 131 tumors that were close to the diaphragm (distance between tumor and diaphragm ≤ 5 mm) in 117 patients with liver cancer. The tumors were divided into a < 3.0 cm group (Group I, n= 101) and a ≥ 3.0 cm group (Group II, n= 30) based on tumor diameters. The complications within 2 weeks following treatment were counted, and the safety and short-term efficacy of MWA were analyzed.

Dysregulated Inflammation in Response to Hypoxia‐Confounded Injury

Traumatic limb injury can cause extensive blood vessel damage that impairs oxygen and nutrient delivery to nearby tissues, resulting in a hypoxic state. The normal course of tissue repair involves a proper balance of pro‐ and anti‐inflammatory signaling; this balance is essential for tissue recovery as it aids in the destruction, containment or removal of pathogens and facilitates the repair of damaged tissue. However, in periods of extended hypoxia‐confounded injury, inflammation may become dysregulated. The mechanisms by which extended hypoxia may influence inflammatory cell activation during the acute recovery period are unknown. We therefore sought to create an in vitro wound model of sustained hypoxia to investigate inflammatory cell activation during this acute recovery period. We hypothesized that sustained hypoxia would result in greater immune cell activation over 72 hours compared to normoxia.We completed several experiments utilizing human monocytes (U937 cells), human dermal fibroblasts (HDFs), and human umbilical vascular endothelial cells (HUVECs) exposed to normoxia (~21% O2) or hypoxia (~1% O2) for 24, 48, or 72 hours. We sought to assess the impact of sustained hypoxia on cell proliferation (scratch wound assay) and immune cell activation (macrophage adhesion; transmigration of macrophages; expression of cell surface markers CD11b and CD14) at each of the time points listed above.We found that hypoxia impaired endothelial cell proliferation in a scratch wound assay, decreasing their ability to cover the gap area after 72 hours. We additionally found that macrophage transmigration was increased in response to hypoxia and that this result was correlated with increased immune cell proliferation as evidenced by increased cell surface expression of CD11b and CD14. We believe these results will provide valuable insight into the effect of sustained hypoxia on inflammatory signaling, and perhaps more importantly, the time course of signaling changes following hypoxia‐confounded injury.

Mechanisms of Jzu4Me, a novel inhibitor of vascular endothelial growth factor induced angiogenesis and tumor angiogenesis

BackgroundAngiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells. It plays a critical role in the growth and spread of cancer, due to the new vessels supply of oxygen and nutrients for tumors to grow, allowing the cancer cells to invade nearby tissue, leading to tumor metastases. Therefore, novel effective therapeutic agents of anti‐angiogenesis are greatly needed. Further studies established that vascular endothelial growth factor (VEGF)‐A is an attractive anti‐angiogenesis target for therapeutic interventions in cancer.Material and methodsIn an effort to develop inhibitors to block VEGF signaling and angiogenesis, benzimidazole derivatives were designed and synthesized, and their angiogenesis inhibitory effects both in vitro and in vivo were evaluated.ResultsAmong these benzimidazole derivatives, Jzu4Me significantly inhibited VEGF‐A‐induced endothelial cells proliferation, migration, invasion and tubular formation, and it also suppressed ex vivo microvessels formation of rat aorta ring induced by VEGF‐A. Moreover, in Matrigel plug implantation mice, Jzu4Me dose‐dependently suppressed the VEGF‐A or tumor‐induced neovascularization in vivo. We also found that Jzu4Me may suppress VEGF‐A signaling in modulating vascular endothelial cell remodeling.ConclusionsOur findings reveal that Jzu4Me inhibits VEGF‐induced angiogenesis via downregulation of VEGFR2‐mediated signaling, suggesting that Jzu4Me has high potential to be developed into a novel therapeutic agent for treating angiogenesis.

1-Aminocyclopropane-1-Carboxylate Oxidase Induction in Tomato Flower Pedicel Phloem and Abscission Related Processes Are Differentially Sensitive to Ethylene.

Ethylene has impact on several physiological plant processes, including abscission, during which plants shed both their vegetative and reproductive organs. Cell separation and programmed cell death are involved in abscission, and these have also been correlated with ethylene action. However, the detailed spatiotemporal pattern of the molecular events during abscission remains unknown. We examined the expression of two tomato ACO genes, LeACO1, and LeACO4 that encode the last enzyme in ethylene biosynthesis, 1-aminocyclopropane-1-carboxylate oxidase (ACO), together with the expression of other abscission-associated genes involved in cell separation and programmed cell death, during a period of 0–12 h after abscission induction in the tomato flower pedicel abscission zone and nearby tissues. In addition, we determined their localization in specific cell layers of the flower pedicel abscission zone and nearby tissues obtained by laser microdissection before and 8 h after abscission induction. The expression of both ACO genes was localized to the vascular tissues in the pedicel. While LeACO4 was more uniformly expressed in all examined cell layers, the main expression site of LeACO1 was in cell layers just outside the abscission zone in its proximal and distal part. We showed that after abscission induction, ACO1 protein was synthesized in phloem companion cells, in which it was localized mainly in the cytoplasm. Samples were additionally treated with 1-methylcyclopropene (1-MCP), a competitive inhibitor of ethylene actions, and analyzed 8 h after abscission induction. Cell-layer-specific changes in gene expression were observed together with the specific localization and ethylene sensitivity of the hallmarks of cell separation and programmed cell death. While treatment with 1-MCP prevented separation of cells through inhibition of the expression of polygalacturonases, which are the key enzymes involved in degradation of the middle lamella, this had less impact on the occurrence of different kinds of membrane vesicles and abscission-related programmed cell death. In the flower pedicel abscission zone, the physical progressions of cell separation and programmed cell death are perpendicular to each other and start in the vascular tissues.

Uncertainties of cumulative dose assessment for prostate IMRT

Intensity-modulated radiation therapy (IMRT) is capable of providing conformal doses to the target volume while minimizing doses to nearby normal tissue for radiotherapy of localized prostate cancer (1). However, the clinical gains of prostate IMRT may be limited by geometric uncertainties of a patient. The prostate movement between fractions, i.e., inter-fractional motion, is associated with patient setup uncertainty as well as internal organ displacement between fractions. The inter-fractional motion contributes to the deviation in the delivered doses to the target volume and organs at risk (OARs) (2). Depending on the filling state of the rectum and bladder, the prostate can move by more than 1 cm (3,4). Image guidance before each fraction can reduce these errors and deliver a precise prescription dose to the target volume while sparing doses to OARs. On the other hand, intra-fractional motion refers to the external patient movement as well as internal organ motion during the actual treatment. The major intra-fractional motion of the prostate gland is generally due to changes of gas in the rectum and surrounding digestive track (5). This temporal behavior of prostate motion can vary rapidly and substantially, which could result in large discrepancies between planned doses and actually delivered doses to a patient.

Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

Activation of hip prostheses in high energy radiotherapy and resultant dose to nearby tissue.

High energy radiotherapy can produce contaminant neutrons through the photonuclear effect. Patients receiving external beam radiation therapy to the pelvis may have high‐density hip prostheses. Metallic materials such as those in hip prostheses, often have high cross‐sections for neutron interaction. In this study, Thackray (UK) prosthetic hips have been irradiated by 18 MV radiotherapy beams to evaluate the additional dose to patients from the activation products. Hips were irradiated in‐ and out‐of field at various distances from the beam isocenter to assess activation caused in‐field by photo‐activation, and neutron activation which occurs both in and out‐of‐field. NaI(Tl) scintillator detectors were used to measure the subsequent gamma‐ray emissions and their half‐lives. High sensitivity Mg, Cu, P doped LiF thermoluminescence dosimeter chips (TLD‐100H) were used to measure the subsequent dose at the surface of a prosthesis over the 12 h following an in‐field irradiation of 10,000 MU to a hip prosthesis located at the beam isocenter in a water phantom. 53Fe, 56Mn, and 52V were identified within the hip following irradiation by radiotherapy beams. The dose measured at the surface of a prosthesis following irradiation in a water phantom was 0.20 mGy over 12 h. The dose at the surface of prostheses irradiated to 200 MU was below the limit of detection (0.05 mGy) of the TLD100H. Prosthetic hips are activated by incident photons and neutrons in high energy radiotherapy, however, the dose resulting from activation is very small.

Chronic Suppurative Lung Disease in Children: Definition and Spectrum of Disease.

The most common clinical suppurative lung conditions in children are empyema, lung abscess, and bronchiectasis, and to a less often necrotizing pneumonia. Until recently, bronchiectasis was the most common form of persistent suppurative lung disease in children. Protracted bacterial bronchitis is a newly described chronic suppurative condition in children, which is less persistent but more common than bronchiectasis (1). In addition, the term “chronic suppurative lung disease” has been used recently to describe the clinical features of bronchiectasis when the radiographic features needed to make a diagnosis of bronchiectasis are absent. Webster’s New College Dictionary defines suppuration as the process of forming and/or discharging pus. Pus is a body fluid resulting from intense inflammation in response to infection that leads to neutrophil influx and apoptosis, microbial clearance, and often necrosis of nearby tissue. Pus is primarily composed of white blood cell debris.

Late endocarditis of Amplatzer septal occluder device in a child

Endocarditis can occur early or late on any intra cardiac devices, and ASD closure devices are not an exception for that. If detected late, there is a high possibility of endocarditis spreading to nearby tissues including valves. Here, we report a case of a child who has developed endocarditis of Amplatzer septal occluder device late after 6 months of implantation, who was successfully operated with device extraction and mitral valve replacement and pericardial patch closure of the primary atrial septal defect.

Future of circulating tumor cells in the melanoma clinical and research laboratory settings

Circulating tumor cells (CTC) have become a field of interest for oncologists based on the premise that they constitute the underpinning for metastatic dissemination. The lethal nature of cancer is no longer attributed to solid tumor formation, but rather to the process of metastasis; shifting the focus of current studies towards the isolation and identification of metastatic progenitors, such as CTCs. CTCs originate from primary tumor masses that undergo morphologic and genetic alterations, which involve the release of mesenchymal-like cancer cells into the bloodstream, capable of invading nearby tissues for secondary tumor development. Cancerous cells contained in the primary tumor mass acquire the motile mesenchymal phenotype as a result of the Epithelial-to-Mesenchymal Transition, where substantial variations in protein expression and signaling pathways take place. CTCs that migrate from the primary tumor, intravasate into the systemic vasculature, are transported through the bloodstream, and invade tissues and organs suitable for secondary tumor development. While only a limited number of CTCs are viable in the bloodstream, their ability to elude the immune system, evade apoptosis and successfully metastasize at secondary tumor sites, makes CTCs promising candidates for unraveling the triggers that initiates the metastatic process. In this article, these subjects are explored in greater depth to elucidate the potential use of CTCs in the detection, disease staging and management of metastatic melanoma.

Enhancing capillary blood collection: The influence of nicotinic acid and nonivamide

Nicotinic acid and nonivamide are often applied topically during capillary blood collection to induce vasodilation. These molecules may have an influence on immune effector cell activity in nearby tissues. This study investigates whether the induction of flushing by nicotinic acid and nonivamide causes an inflammatory response that influences the composition of immune cells present in a capillary blood sample. Females aged between 18 and 30years old provided capillary blood samples. Experimental samples were taken from an earlobe treated with nicotinic acid and nonivamide with controls obtained from the untreated earlobe. Immunophenotypic analyses were conducted using polychromatic flow cytometry to determine whether any changes occurred in leucocyte subpopulations (CD3, CD4, CD8, CD19, CD56, and CD14) and granulocytic functional-related surface antigen markers (CD11b, CD18, CD16b, and CD66b). No significant differences were observed between experimental and control samples in the mean percent of parent for the lymphocyte, monocyte, or granulocyte subpopulations, or in the median fluorescence intensity of particular surface markers expressed on these leucocytes. The topical application of nicotinic acid and nonivamide is a possible method to improve capillary blood collection for immunological assessments. The use of these agents may increase the safety and compliance of patients who suffer from needle phobia or are unable to provide venous blood samples.

Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora

Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species.