bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Perinatal and Adult Multi-Innervation in Human Laryngeal Muscle Fibers
Authors: Périé Sophie , St Guily Jean Lacau , Sebille Alain
Published: October 2014

The innervation of human laryngeal myofibers appears distinct from that of skeletal myofibers, because some of them exhibit multiple neuromuscular junctions. We attempted to understand the significance of the multi-innervation phenomenon by comparing intrinsic laryngeal muscles obtained from autopsies of a fetus, a stillbirth, and a 7-month-old infant to muscles from adults. In longitudinal sections (40 to 60 μm thick) the cholinesterase sites and the nerve terminals were stained simultaneously for light microscopy. Multi-innervation reached no more than 23% at 7 months, and this percentage decreased notably with age. Until 7 months, end plates were innervated either by single or by multiple axons (unineuronal and polyneuronal innervation), whereas in adults, the pattern was exclusively unineuronal. Moreover, the structure of neuromuscular junctions in the young was limited to 1 spot of acetylcholinesterase, while in adults the end plate zones increased in size and complex axon terminals were observed. These observations are consistent with a delayed maturation of human laryngeal innervation compared to that of skeletal muscles.
Comparison of Nerve Banking Techniques in Delayed Laryngeal Reinnervation
Authors: Andrews Robert J. , Ye Ming , Peterson K. Linnea , Sercarz Joel A. , Blackwell Keith E. , Kevorkian Kevin , Berke Gerald S.
Published: October 2014

Successful laryngeal transplantation will require adequate reinnervation of the larynx to allow phonation, coordinated swallowing, and respiration. A delay between laryngectomy and transplantation would be necessary in oncology patients because of the need for immunosuppression. In these patients, reinnervation of the donor organ would require “banking” and recovery of dormant recipient recurrent laryngeal nerves (RLNs). This pilot study was undertaken to compare the effectiveness of RLN storage using 1 of 2 techniques: 1) inserting the nerve into a muscle pocket or 2) anastomosing the proximal RLN stump to the ansa cervicalis. Six months following nerve transection and “banking,” the proximal anterior branch of the RLN was reanastomosed to the distal anterior segment and the posterior branch was anastomosed directly to the posterior cricoarytenoid muscle. Tensionometry, image analysis, and electromyographic data were collected 1 year later. Results show reinnervation of adductors and abductors with both techniques. Banking of the RLN branches during total laryngectomy is effective and should permit delayed physiological reinnervation following laryngeal transplantation.
Fluorescence-Guided Biopsy in the Diagnosis of an Unknown Primary Cancer in Patients with Metastatic Cervical Lymph Nodes
Authors: Kulapaditharom Boonchu , Boonkitticharoen Vipa , Kunachak Somyos
Published: October 2014

This study was conducted to determine the effectiveness of fluorescence-guided biopsy in diagnosis of unknown primary cancers in the head and neck. Thirteen patients with biopsy-proven cervical node metastases were evaluated prospectively with laser-induced fluorescence (LIF) endoscopy in parallel to panendoscopy. Among the 13 positive sites suggested by LIF imaging, 5 were confirmed by histopathology as squamous cell carcinoma, 4 as dysplasia, 2 as inflammation, and 2 as normal. Panendoscopy with random biopsies located 2. The 2 cases of squamous cell carcinomas discovered conventionally were identified by histologic sections from ipsilateral tonsillectomy. In this series, the unknown primary cancers were localized by LIF imaging and conventional means at rates of 38.5% and 15.4%, respectively. The LIF imaging not only aided in revealing a greater proportion of occult primary cancers, but also helped in reducing the number of unnecessary biopsies. Fluorescence-guided biopsy diagnosis provides useful information for therapeutic planning with curative aim or for adequate palliation.
Inner Ear Damage in Torp-Operated Ears: Experimental Study on Danger from Environmental Air Pressure Changes
Authors: Pau Hans Wilhelm
Published: October 2014

In some cases of sudden inner ear hearing loss in ears with a total ossicular replacement prosthesis, the prosthesis has been found to be penetrating the footplate. Some authors have assumed an external pressure increase for this event. In this study I tried to estimate experimentally the pressure needed for perforating a normal footplate in a temporal bone model. From the data I concluded that “cracking” the footplate can hardly be due to 1 major event of increased pressure. On the other hand, different mechanisms making the footplate a “weak spot” must be discussed and further investigated. In those cases, secondary to thinned or even perforated footplates, environmental pressure changes may be dangerous.
Mastoid Buffering Properties: I. Gas Partial Pressures
Authors: Raveh Eyal , Mover-Lev Haya , Sadé Jacob , Guney Selcuk
Published: October 2014

Differences in the gas partial pressures between the middle ear (ME) cavity and the blood are an important factor in ME gas economy. Differences in gas partial pressures between various regions of the ME-mastoid air cell system (ME-MACS) could play a role as well. To determine whether gas partial pressure differences do occur between various compartments in the ME, we measured the rate of gas diffusion from one compartment to another in both an artificial model and in the ME-MACS of human temporal bones. The rate of gas diffusion between various areas of the ME and the mastoid tip was found to be rapid, with a half-life on the order of 2 minutes (range 0.8 to 5.3 minutes). We suggest that this high diffusion rate prevents the buildup of significant differences in gas composition in the ME-MACS system, which can therefore be regarded as a homogeneous gas pocket.
Leiomyosarcoma of the Larynx
Authors: Thomas Shawn , McGuff Howard S. , Otto Randal A.
Published: October 2014

Leiomyosarcoma involving the larynx is extremely rare and may be difficult to diagnose. Likewise, because of the rarity of this lesion, little information exists with regard to long-term follow-up or optimal management. Reported here is a review of the literature and a case report of a patient with leiomyosarcoma of the larynx treated by surgery alone with 5 years of follow-up.
Endoscopic Diverticulotomy for the Treatment of Zenker's Diverticulum: Results in 102 Patients with Staple-Assisted Endoscopy
Authors: Narne Surendra , Cutrone Cesare , Chella Barbara , Bonavina Luigi , Peracchia Alberto
Published: October 2014

Endoscopic diverticulotomy for the treatment of Zenker's diverticulum has been reported infrequently in the literature and has engendered considerable controversy. Between March 1992 and September 1996, we attempted to treat 102 patients with endoscopic treatment for pharyngoesophageal diverticula. In 98 patients, the endoscopic surgery was successfully completed. Conversion to open surgery was required in 4 patients (3.92%). One cartridge of staples in 16 patients (16.32%), 2 cartridges in 78 patients (79.59%), and 3 cartridges in 4 patients (4.08%) were used, according to the size of the diverticulum; the median duration of the procedure was 20 minutes (10 to 60 minutes). No postoperative morbidity or mortality was recorded. Oral feeding was started following radiologic control after a median of 2 days; the median hospital stay was 4 days. The median follow-up is 16 months (1 to 45 months). Four patients operated on before the introduction of the modified stapler showed a persistent diverticular pouch: 3 underwent repeat endoscopic operation, and 1 underwent conventional open surgery. All treated patients are asymptomatic. Manometric study performed in 15 patients showed a significant reduction of basal upper esophageal sphincter pressure compared to preoperative data (48.30 ± 21.74 versus 29.38 ± 5.68 mm Hg; p < .01). We therefore recommend endoscopic diverticulotomy, considering that the procedure is relatively safe and effective, with minimal patient discomfort, and the results are equal to those of the external approach. This procedure offers the advantages of short hospitalization, rapid convalescence, brief operative time, absence of skin incision, predictable resolution of symptoms, and reduced morbidity.
Distant Lymphatic Metastasis from Head and Neck Cancer
Authors: Alavi Sassan , Namazie Ali , Sercarz Joel A. , Wang Marilene B. , Blackwell Keith E.
Published: October 2014

A predictable pattern of metastasis based on tumor histology and site of origin has been well documented for most cancers that arise in the head and neck region. The current study demonstrates that this predictable pattern of metastasis can be significantly impacted by previous therapy, resulting in unusual patterns of metastasis in patients with recurrent tumors. A retrospective case series of 5 patients with head and neck carcinomas who developed metastases to distant lymph nodes is presented. All patients underwent surgery and radiotherapy to the primary tumor and regional lymphatics at the time of their initial treatment. All of the patients developed a local recurrence less than a year before the detection of distant lymphatic metastases. Cytology or excision confirmed metastases to the axillary, inguinal, or anterior intercostal lymph nodes. All of the patients underwent aggressive surgery for attempted cure of the local recurrence shortly before the presence of distant lymphatic metastases was clinically recognized. The metastatic workup of patients with carcinomas of the head and neck frequently includes examination of the regional lymph nodes as well as chest radiography, liver function tests, and serum calcium determination. This evaluation may fail to detect metastases to distant lymph nodes in patients who present with recurrent or second primary cancers. Such patients should undergo careful examination of all major lymph node-bearing regions of the body when being evaluated for the presence of distant metastases.
Effect of Carbogen Inhalation on Peripheral Tissue Perfusion and Oxygenation in Patients Suffering from Sudden Hearing Loss
Authors: Kallinen Johanna , Kuttila Kari , Aitasalo Kalle , Grénman Reidar
Published: October 2014

The effects of repeated carbogen inhalation on peripheral tissue perfusion and oxygenation were assessed in 5 patients suffering from sudden hearing loss by means of continuously measured subcutaneous tissue oxygen and carbon dioxide tension, transcutaneous oxygen tension, laser Doppler red cell flux, and fingertip temperature. The subcutaneous oxygen tension increased clearly during the carbogen inhalation periods, and also, a smaller increase in subcutaneous carbon dioxide tension was simultaneously noticed. The changes in transcutaneous oxygen tension were even greater and the latency was shorter as compared with the subcutaneous gas tensions. The laser Doppler measurements showed no signs of vasoconstriction during the study. In conclusion, carbogen inhalation increases peripheral tissue oxygenation without microvascular vasoconstriction and with only a minor retention of carbon dioxide.
Expression of NPY Y1 and CGRP1 Receptors in Human Nasal Mucosa: Implications in Allergic Rhinitis
Authors: Uddman Rolf , Cardell Lars Olaf , Cantera Leonor , Edvinsson Lars
Published: October 2014

Numerous nerve fibers containing neuropeptide Y (NPY) and calcitonin gene—related peptide (CGRP) have been found in the human nasal mucosa by means of immunocytochemistry. We detected NPY Y1 and CGRP1 receptors at the same location using reverse transcriptase-polymerase chain reaction. The possibility of local release in connection with specific target receptors suggests a role for endogenous NPY and CGRP in the regulation of vascular tone, glandular secretion, and epithelial functions.
Radiation-Induced Hearing Impairment in Patients Treated for Malignant Parotid Tumor
Authors: Liao Chun-Ta , Wang Chun-Chieh , Chen Wen-Cheng , Tsai Hsin-Cheng , Tang Simon G. , Yeh Jami-Yi , Hong Ji-Hong
Published: October 2014

Radiation-induced hearing loss was evaluated in 21 patients with unilateral malignant parotid tumors treated with surgery and radiotherapy. The contralateral ear was used as a control. Eight patients (38%) were found to have a reduction in static compliance of the tympanic membrane (type B tympanogram) in the irradiated ear. By audiometry, significant hearing loss was found in 9 patients (43%). These hearing losses were mainly sensorineural, as shown by a similar reduction in both air and bone conduction, although mixed-type hearing loss existed in some patients. A statistically significant difference in incidence of 67% versus 0% (p = .0085) was noted for patients with a cochlear dose of greater than or equal to 60 Gy, in comparison to those receiving doses of less than 60 Gy. A type B tympanogram was also found to be a prognostic factor for significant sensorineural hearing loss. Patients with type B tympanograms had a much higher incidence of significant sensorineural hearing loss than those with type A tympanograms (88% versus 15%, p = .02). This study clearly shows that radiotherapy can induce significant hearing impairment, especially when the cochlear doses are higher than 60 Gy.
Progressive Sensorineural Hearing Impairment in Professional Fishery Divers
Authors: Haraguchi Hidetoshi , Noguchi Yoshihiro , Ohgaki Tohru , Sugimoto Taro , Okubo Jin , Komatsuzaki Atsushi
Published: October 2014

There have been many reports of a high rate of hearing impairment in divers. A prospective study was performed to determine whether sensorineural hearing acuity in the same divers deteriorated faster than in a normal population as they continued diving. After an observation period of approximately 5 years, audiometric examination was performed on a group of professional fishery divers who had normal hearing or sensorineural hearing loss at the time of initial study. Thirty-three ears of 18 divers were included in statistical analyses. The average hearing deterioration in the divers in 5 years, after elimination of the aging effect, was 6.6 dB (SD 4.5) and was statistically significant. We concluded that the hearing acuity of our subjects deteriorated faster than that of normal Japanese.
Spontaneous Vertebral Artery Dissection Mimicking Acute Vertigo Case Report
Authors: Braverman Itzhak , River Yaron , Eliashar Ron , Rappaport Jamie M. , Elidan Josef
Published: October 2014

A patient with acute vertigo, and normal findings on neurologic examination, was found to have vertebral artery dissection (VAD). This case shows that the clinical picture of VAD can mimic vertigo of labyrinthine (ie, peripheral) origin.
Clinicopathological Consultation Micrometastases: Have They an Impact on Prognosis?
Authors: Ferlito Alfio , Devaney Kenneth O. , Devaney Stephanie L. , Rinaldo Alessandra , Carbone Antonino
Published: October 2014

Current routine histopathologic methods may fail in detecting lymph node micrometastases, while the introduction of newer, sensitive techniques, such as immunohistochemistry and molecular analysis, can improve their detection. The literature reveals that the presence of micrometastases has clinical and prognostic implications.
The night-time city. Four modes of exclusion: Reflections on the Urban Studies special collection
Authors: Hadfield Phil
Published: October 2014

This article presents commentary and analysis on the Urban Studies special collection on the night-time city. The collection highlights burgeoning interest in the urban night from across the social sciences and helps consolidate what might be referred to as the ‘third wave’ of research on the evening and night-time economy (ENTE). The collection addresses the challenges of 21st century place-making after dark in a variety of international contexts. This commentary interprets individual contributions to this collection in the light of the author’s research experience within an evolving and increasingly sophisticated field of knowledge. The articles have, I suggest, power relations, social exclusion and social sustainability as their most prominent meta-themes. I propose a new conceptual model for the interpretation of situated assemblages of power, capacity and influence, as operating across four overlapping modes of urban governance.
Pneumomediastinum and pneumoperitoneum on computed tomography after peroral endoscopic myotomy (POEM): postoperative changes or complications?
Authors: Yang Shan , Zeng Meng-su , Zhang Zhi-yong , Zhang Hao-ling , Liang Liang , Zhang Xing-wei
Published: October 2014

Background

Many of the acute alterations after peroral endoscopic myotomy (POEM) may be of little clinical significance, while others may herald major clinical problems. The question whether pneumomediastinum/pneumoperitoneum is a normal postoperative finding after POEM, or should be regarded as a sign of a complication needs to be evaluated. Familiarity with these findings in computed tomography (CT) is essential for radiologists.

Purpose

To evaluate whether or not pneumomediastinum/pneumoperitoneum detected by chest CT is a sign of a complication after POEM using CO2 insufflation for esophageal achalasia.

Material and Methods

One hundred and eight patients with esophageal achalasia who underwent chest CT within 30 hours after POEM were included. CT findings were retrospectively reviewed by two radiologists in consensus. The correlation between pneumomediastinum and/or pneumoperitoneum shown on CT and the development of complications was analyzed.

Results

Abnormal findings were identified on post-treatment CT, including pneumomediastinum and/or pneumoperitoneum (53.7%, 58/108), pneumothorax (0.9%, 1/108), subcutaneous emphysema (29.6%, 32/108), pleural effusion (69.4%, 75/108), segmental atelectasis of lung tissue (29.6%, 32/108), minor inflammation of lungs (69.4%, 75/108), and ascites (0.9%, 1/108). Pneumomediastinum and pneumoperitoneum were observed simultaneously in 29 cases. The incidence rate of mild complications was high (79.6%, 86/108), while the rate of severe complications was low (2.8%, 3/108). There was no significant correlation between the occurrence of pneumomediastinum and/or pneumoperitoneum on CT and the development of complications ( P = 0.542), or the development of severe complications including delayed hemorrhage, esophageal perforation, and retroperitoneal abscess.

Conclusion

Pneumomediastinum and pneumoperitoneum detected by CT occur frequently after POEM and may be regarded as normal postoperative changes.
Ankle Fracture Spur Sign Is Pathognomonic for a Variant Ankle Fracture
Authors: Hinds Richard M. , Garner Matthew R. , Lazaro Lionel E. , Warner Stephen J. , Loftus Michael L. , Birnbaum Jacqueline F. , Burket Jayme C. , Lorich Dean G.
Published: October 2014

Background:

The hyperplantarflexion variant ankle fracture is composed of a posterior tibial lip fracture with posterolateral and posteromedial fracture fragments separated by a vertical fracture line. This infrequently reported injury pattern often includes an associated “spur sign” or double cortical density at the inferomedial tibial metaphysis. The objective of this study was to quantitatively establish the association of the ankle fracture spur sign with the hyperplantarflexion variant ankle fracture.

Methods:

Our clinical database of operative ankle fractures was retrospectively reviewed for the incidence of hyperplantarflexion variant and nonvariant ankle fractures as determined by assessment of injury radiographs, preoperative advanced imaging, and intraoperative observation. Injury radiographs were then evaluated for the presence of the spur sign, and association between the spur sign and variant fractures was analyzed.

Results:

The incidence of the hyperplantarflexion variant fracture among all ankle fractures was 6.7% (43/640). The spur sign was present in 79% (34/43) of variant fractures and absent in all nonvariant fractures, conferring a specificity of 100% in identifying variant fractures. Positive predictive value and negative predictive value were 100% and 99%, respectively.

Conclusion:

The ankle fracture spur sign was pathognomonic for the hyperplantarflexion variant ankle fracture. It is important to identify variant fractures preoperatively as patient positioning, operative approach, and fixation construct of variant fractures often differ from those employed for osteosynthesis of nonvariant fractures. Identification of the spur sign should prompt acquisition of advanced imaging to formulate an appropriate operative plan to address the variant fracture pattern.

Level of Evidence:

Level III, retrospective comparative study.
Decarceration and its possible effects on inmates, staff, and communities
Authors: Garland Brett , Hogan Nancy , Wodahl Eric , Hass Aida , Stohr Mary K , Lambert Eric
Published: October 2014

Few current criminal justice scholars, practitioners, and politicians expected to witness the phenomenon of decreasing correctional populations. Yet, there is evidence at local, state, and regional levels of significant declines in the growth of incarceration and even decreases in the size of prisoner populations. In this article we delineate the extent of decarceration and examine the context in which it has occurred. We then explore possible positive and negative outcomes resulting from decarceration and conclude with an agenda for advancing a decarceration movement.
Democratising punishment: Sentencing, community views and values
Authors: Roberts Julian V , de Keijser Jan W
Published: October 2014

This essay explores and critiques a theory of criminal justice which privileges the role of public intuitions about punishment over more traditional influences on sentencing principles and practice. This movement may be termed ‘Democratising Punishment’ and it has important consequences for sentencing in all jurisdictions. Several recent books advocate reforms such as deriving sentencing principles from public opinion research or sentencing by juries rather than legal professionals. In the essay we critique this perspective and note the threats to principled sentencing arising from greater public involvement in the sentencing of offenders.
What is a “history of the present”? On Foucault’s genealogies and their critical preconditions
Authors: Garland David
Published: October 2014

In this article Michel Foucault’s method of writing a “history of the present” is explained, together with its critical objectives and its difference from conventional historiography. Foucault’s shift from a style of historical research and analysis conceived as “archaeology” to one understood as “genealogy” is also discussed, showing how the history of the present deploys genealogical inquiry and the uncovering of hidden conflicts and contexts as a means of re-valuing the value of contemporary phenomena. The article highlights the critical observations of present-day phenomena from which a history of the present begins, paying particular attention to Foucault’s concept of “ dispositif” and his method of problematization. Foucault’s analyses of Bentham’s Panopticon, of the disciplinary sources of the modern prison, and of the technology of confession are discussed by way of illustration.
Infrared Spectroscopy of Human Cells and Tissue: Detection of Disease
Authors: Lasch Peter , Chiriboga Luis , Yee Herman , Diem Max
Published: October 2014

An objective method for the analysis of tissue section is described that uses the chemical composition of the tissue, rather than cell morphology, as an indicator for the state of health of the cells in the tissue. The chemical composition of cells and tissue, and small variations therein, are determined by an objective, quantitative spectral measurement carried out in the infrared spectral region. This method does not utilize any stains or chemical treatment of the sample, but uses an inherent optical property of all materials. The spectral information is converted to false color images by unsupervised mathematical methods. The false color maps reveal the same anatomical features of the tissue that can be confirmed using a variety of common histopathological procedures, and may be used to differentiate between normal and diseased areas of the tissue.
Clinical Applications of Proton MR Spectroscopy in Oncology
Authors: Kwock Lester , Smith J. Keith , Castillo Mauricio , Ewend Matthew G. , Cush Sharon , Hensing Thomas , Varia Mahesh , Morris David , Bouldin Thomas W.
Published: October 2014

Proton magnetic resonance spectroscopy (H1-MRS) has been increasingly receiving more attention from radiologists, neurosurgeons, radiation and medical oncologists in the “in situ” clinical evaluation of human tumors. The utilization of H1-MRS, especially in human brain tumors, coupled to both routine magnetic resonance imaging (MRI) and functional MRI techniques provides greater information concerning tumor grading and extension and characterization of the normal surrounding tissue than what is possible with any other imaging technique alone. In this paper, we will review the current status of proton MR spectroscopy with emphasis on its clinical utility to diagnose tumors, its utility in planning surgical and radiation therapy interventions, and in its use in monitoring tumor treatment.
Alphavirus Vectors as Tools in Cancer Gene Therapy
Authors: Lundstrom Kenneth
Published: October 2014

Alphavirus vectors, particularly those based on the replicon of Semliki Forest virus, have shown great potential as gene delivery vehicles for various applications in cancer gene therapy. The rapid production of high-titer recombinant SFV particles, which show impressive transduction rates in various mammalian cell lines, primary cultures and in vivo, results in high levels of transgene expression. Additionally, SFV vectors induce apoptosis in transduced host cells, which can further increase their efficiency in tumor therapy. Because of the broad host range some attempts to target the gene delivery have been engineered for Sindbis virus vectors, where IgG binding domains of protein A have been introduced into the envelope structure of the recombinant particles to allow attachment of virus to host cells through the interaction of protein A with monoclonal antibodies. SFV vectors have also been employed for the production of retrovirus-like particles for establishment of long-term gene expression. Tumor vaccine approaches have been taken by injection of SFV vectors as naked RNA molecules, DNA plasmids or recombinant particles to achieve both therapeutic and prophylactic efficacy. The continuous improvement of alphavirus vectors will further expand the application range in the future.
X-Ray Optics for Better Diagnostic Imaging
Authors: MacDonald C. A. , Gibson W. M. , Peppler W. W.
Published: October 2014

Polycapillary x-ray optics provide an innovative new way to control x-ray beams. Placing these optics after the object to be imaged provides very efficient rejection of Compton scatter, while allowing image magnification without loss of resolution, image demagnification, or image shaping to match with digital detectors. Measured scatter rejection optics had primary transmissions greater than 50% and scatter transmission of less than 1%. For a 5-cm thick Lucite phantom, this resulted in a contrast enhancement of nearly a factor of two at 20 keV and three at 40 keV. The magnification from the tapered capillary optics improved the MTF at all frequencies out to 1.8 times the original system resolution. Increases below the system resolution are most important because clinically relevant structures generally occupy lower spatial frequencies.

Alternatively, placing a collimating optic and diffracting crystal before the patient provides sufficient monochromatic beam intensity for medical imaging. Contrast, resolution, and intensity measurements were performed with both high and low angular acceptance crystals. At 8 keV, contrast enhancement was a factor of 5 relative to the polychromatic case, in good agreement with theoretical values. At 17.5 keV, monochromatic subject contrast was more than a factor of 2 times greater than the conventional polychromatic contrast. An additional factor of two increase in contrast, for a total factor of four, is expected from the removal of scatter in a large beam clinical system. The measured angular resolution after the crystal was 0.4 mrad for a silicon crystal.
A Phase II Study of Concomitant Hyperfractionated Radiation Therapy and Double Dose Intra-Arterial Cisplatin for Squamous Cell Carcinoma of the Head and Neck
Authors: Regine William F. , Valentino Joseph , Arnold Susanne M. , Sloan David , Kenady Daniel , Strottmann James , Mohiuddin Mohammed
Published: October 2014

This successor phase II study evaluates the tolerability and efficacy of concomitant hyper-fractionated radiation therapy (HFX-RT) and double dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In doing so, this study represents further resurgence of the potential use of IA chemotherapy in the management of SCCHN. This has been enabled by the evolution of angiographic catheter/microcatherter technology. Between 1997 and 1999, 24 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8–81.6 Gy at 1.2 Gy bid over 6–7 weeks) and high-dose IA cisplatin (150mg/m2 given at the start of and during RT boost treatment [start of week 6 and 7]). Twenty-two patients (92%) had T4 disease and 14 (58%) N2/ N3 disease. Acute toxicity was limited to two grade 4 (8%) and 19 grade 3 (79%) mucosal events; and single grade 3 hematologic, infectious and skin events. Eight patients (33%) were unable to receive the second planned dose of IA cisplatin. Twenty-two patients had complete response (92%) at the primary site. Among 17 patients with positive neck disease 12 (71%) achieved complete response in the neck. Follow-up ranges from 7–30 months (median = 18 months) with 14 patients alive without disease, 2 alive with disease, 7 dead of disease and 1 dead of intercurrent disease. While concomitant HFX-RT and double dose IA cisplatin as used in this study is associated with encouraging response rates in this highly unfavorable subset of patients with locally advanced SCCHN it was not feasible. Future investigation of this novel treatment strategy utilizing modern angiographic catheter/microcatherter technology will involve a single dose of IA cisplatin with HFX-RT and dose intensification using neoadjuvant therapy.
Plasmid DNA Electrotransfer: A New Non Viral Method for Gene Therapy in Oncology
Authors: Bureau M. F. , Scherman D.
Published: October 2014

With some defined conditions, electric pulses delivery to tissue in vivo can greatly enhance DNA transfection. We here describe the application in oncology of intratumoral or intramuscular DNA electrotransfer by using muscle as a secretory tissue of transgenic proteins displaying anticancer properties.
Effect of Electrically Mediated Intratumor and Intramuscular Delivery of a Plasmid Encoding IFN α on Visible B16 Mouse Melanomas
Authors: Heller Loree C. , Ingram Stephanie F. , Lucas M. Lee , Gilbert Richard A. , Heller Richard
Published: October 2014

Interferon α may be used as a single agent therapy for metastatic malignant melanoma or as an adjuvant to chemotherapy. Delivery of interferon α by gene therapy offers an alternative to recombinant protein therapy. Electrically mediated delivery enhances plasmid expression in a number of tissues, for instance skin, liver, muscle and tumors including melanomas. Here we compare the effect of delivery of a plasmid encoding mouse interferon α on growth of visible B16 mouse melanomas following electrically mediated delivery to muscle or directly to the tumor. Intratumoral delivery of interferon α plasmid not only slows melanoma growth, but induces complete, long term, regression. This effect was not observed after intramuscular delivery.
Contributions of Proteome Profiling to the Molecular Analysis of Cancer
Authors: Wang Hong , Hanash S. M.
Published: October 2014

The proteome is the most functional compartment encoded for in the genome. Technologies for protein separation and quantitation, coupled with mass spectrometry for protein identification, have provided the means for proteome profiling of tumor cell lines and tissues that complement genomic and transcriptomic profiling. The application of established and novel proteomic technologies to the molecular analysis of cancer is reviewed.
Application of Proteomics in the Search for Novel Proteins Associated with the Anti-cancer Effect of the Synthetic Cyclin-dependent Kinases Inhibitor, Bohemine
Authors: Kovarova Hana , Halada Petr , Man Petr , Dzubak Petr , Hajduch Marian
Published: October 2014

The purpose of this study was to use the proteomics approach, which is based on high resolution two-dimensional electrophoresis coupled with multivariate correspondence analysis and mass spectrometry, to classify objectively the biochemical basis of the anti-cancer activity of the synthetic cyclin-dependent kinase inhibitor, bohemine (BOH). The changes in the cell cycle and corresponding protein composition of the A549 human lung adenocarcinoma cell line after treatment with BOH were evaluated and proteins differentially expressed in the BOH treated A549 cells, compared to the untreated A549 counterparts, were selected. Thirteen of these candidate proteins associated with the drug effects in vitro were identified by mass spectrometry. Many of these proteins fall into one of three functional categories: i) metabolic pathways (glycolysis, nucleic acid synthesis and NADPH production), ii) stress response and protein folding, and iii) cytoskeleton and exocytosis. Changes in protein expression patterns corresponded to a higher resistance of A549 lung carcinoma cells to BOH when compared to the CEM leukaemia cell line. These protein changes reflect a fine balance of the resistant versus the susceptible phenotype in response to the drug. Since BOH is a selective cyclin-dependent kinase inhibitor, changes in the protein expression pattern can be more generally associated with cell cycle regulation as evidenced by inhibition of cell cycling in A549 cells. Our conclusions further underline the importance of cell cycle control in both the cellular signalling and metabolic pathways.
The Role of Proteomics in the Diagnosis and Outcome Prediction in Colorectal Cancer
Authors: Steinert R. , Buschmann T. , van der Linden M. , Fels L. M. , Lippert H. , Reymond M.A.
Published: October 2014

Colorectal cancer is the second most frequent cancer in Western countries. Exogenous factors play a major role in the aetiology of sporadic colorectal cancer representing about 90% of all cases, hereditary cancers accounting for about 10% of patients. Thus, in the large majority of cases, cell dysfunction in CRC results from multiple rather than single, gene interactions. Numerous cellular events and environmental influences modify gene expression or post-translational protein modifications.

Changes like glycosylation of proteins and lipids which are a common feature in colorectal cancer and influence cancer cell behaviour, cannot be directly detected by genetic studies. Better than genomics studies, functional proteomics studies allow the investigation of environmental factors over time, allowing the monitoring of metabolic responses to various stimuli. However, proteomics studies also have several drawbacks: a) current tools only allow narrow-range analyses, b) identification of proteins of interest remains cumbersome, c) protein studies address multiple compounds of high complexity, d) large amount of proteins are necessary to allow analysis, e) protein research require specific tools, e.g. tagged antibodies, that first have to be developed.

Some protein tests are already in application for CRC: a classical prognostic test in colorectal cancer is based on the detection and quantification of a single protein (CEA) in body fluids. Recently, a screening assay based on APC protein truncation test has also been proposed. However, studies linking large protein expression patterns with clinical outcome in colorectal cancer are still in their infancy. To be able to predict occurrence of disease, and treatment outcome, more studies on genotype-phenotype correlations are needed both in sporadic and in hereditary colorectal cancer.
Factors Controlling Electropermeabilisation of Cell Membranes
Authors: Rols M. P. , Golzio M. , Gabriel B. , Teissié J.
Published: October 2014

Electric field pulses are a new approach for drug and gene delivery for cancer therapy. They induce a localized structural alteration of cell membranes. The associated physical mechanisms are well explained and can be safely controlled. A position dependent modulation of the membrane potential difference is induced when an electric field is applied to a cell. Electric field pulses with an overcritical intensity evoke a local membrane alteration. A free exchange of hydrophilic low molecular weight molecules takes place across the membrane. A leakage of cytosolic metabolites and a loading of polar drugs into the cytoplasm are obtained. The fraction of the cell surface which is competent for exchange is a function of the field intensity. The level of local exchange is strongly controlled by the pulse duration and the number of successive pulses. The permeabilised state is long lived. Its lifetime is under the control of the cumulated pulse duration. Cell viability can be preserved. Gene transfer is obtained but its mechanism is not a free diffusion. Plasmids are electrophoretically accumulated against the permeabilised cell surface and form aggregates due to the field effect. After the pulses, several steps follow: translocation to the cytoplasm, traffic to the nucleus and expression.

Molecular structural and metabolic changes in cells remain mostly poorly understood. Nevertheless, while most studies were established on cells in culture ( in vitro), recent experiments show that similar effects are obtained on tissue ( in vivo). Transfer remains controlled by the physical parameters of the electrical treatment.
Digression on Membrane Electroporation for Drug and Gene Delivery
Authors: Neumann Eberhard , Kakorin Sergej
Published: October 2014

Membrane electroporation (ME) defines an electrical technique to render lipid membranes porous and permeable, transiently and reversibly, by external voltage pulses. Although there are numerous applications of ME to manipulate cells, organelles and tissues in cell biology, biotechnology and medicine, yet the molecular mechanism of ME is only slowly being understood. A general chemical-thermodynamical approach for the quantitative description of cell membrane electroporation has been developed to provide the framework to quantitatively rationalize electroporative cell transformation and electroporative uptake of drug-like dyes into cells, as well as electrolyte efflux from salt-filled electroporated vesicles.

Mechanistically, the electroporative transfer of gene and drug-like dyes involves the coupling between an interactive contact formation of the permeates with the cell surface membrane and the structural electroporation-resealing cycle

[Formula: see text]

where C is the closed and (P) represents a number of different porated membrane states, respectively. The experimentally accessible concentration fraction fp = [(P)] /([C] + [(P)]) of porous states is related to thermodynamic and electro-mechanic parameters such as temperature and the electric field strength, membrane rigidity or curvature. The results of the theoretical approach, mainly based on electrooptical data of lipid vesicles, have been successfully used to analyze single cells and to specify conditions for the practical purpose of direct electroporative gene transfer and drug delivery, in particular in the new medical disciplines of electroporative chemotherapy and electroporative gene vaccination.
Effect of Electrochemotherapy on Muscle and Skin
Authors: Heller Richard , Coppola Domenico , Pottinger Carlos , Gilbert Richard , Jaroszeski Mark J.
Published: October 2014

The efficient delivery of drugs to tumors is an important tool for the treatment of a variety of cancers. Electric pulses have been shown to facilitate the uptake of molecules through the cell membrane. This procedure has been successful in increasing the effectiveness of antitumor agents (electrochemotherapy; ECT). Response rates of >80% have been obtained in both animal and human trials for several types of skin malignancies. The study reported here examined the effect of ECT on normal tissue. The hind limbs of Sprague Dawley rats were treated with 1–3 electroporation sequences in the presence or absence of the drug (bleomycin) which was administered at 4, 8 or 16 units/ml. The treated sites were examined histologically 3, 14 and 56 days later. Limb function was not affected by the treatment and skin and muscle necrosis was only seen at the higher doses.
Electrochemotherapy for the Treatment of Human Sarcoma in Athymic Rats
Authors: Jaroszeski Mark J. , Coppola Domenico , Pottinger Carlos , Gilbert Richard A. , Heller Richard
Published: October 2014

Electrochemotherapy is the combined use of a chemotherapeutic agent and pulsed electric fields. Electrical treatment causes an increase in cell membrane permeability which allows the chemotherapeutic agent to more freely enter the tumor cells. Electrochemotherapy has been under development in clinical trials. This study focused on determining the applicability of electrochemotherapy for treating soft tissue sarcoma using an animal model bearing human sarcomas. The antitumor effects of several concentrations of cisplatin, bleomycin, doxorubicin, and netropsin as single agents delivered with electric pulses were investigated based on post-treatment tumor volumes and histology. Electrochemotherapy treatment resulted in 5% to 88.9% durable complete responses; ECT that employed bleomycin resulted in the highest antitumor effects. This indicates the feasibility of electrochemotherapy as a modality for limb preserving treatments for sarcoma of the extremities.
Transcription Factor Decoy (TFD) in Breast Cancer Research and Treatment
Authors: Piva Roberta , Gambari Roberto
Published: October 2014

Synthetic oligonucleotides have recently been the object of many investigations aimed to develop sequence-selective compounds able to modulate, either positively or negatively, transcription of eukaryotic and viral genes. Alteration of transcription could be obtained by using synthetic oligonucleotides mimicking target sites of transcription factors (the transcription factor decoy -TFD- approach). This could lead to either inhibition or activation of gene expression, depending on the biological functions of the target transcription factors. Since several transcription factors are involved in tumor onset and progression, this issue is of great interest in order to design anti-tumor compounds. In addition to oligonucleotides, peptide nucleic acids (PNA) can be proposed for the modulation of gene expression. In this respect, double-stranded PNA-DNA chimeras have been shown to be capable to exhibit strong decoy activity. In the case of treatment of breast cancer cells, decoy oligonucleotides mimicking CRE binding sites, promoter region of estrogen receptor α gene, NF-kB binding sites have been used with promising results. Therefore, the transcription factor decoy approach could be object of further studies to develop protocols for the treatment of breast cancer. In the future, transcription factors regulating cell cycle, hormone-dependent differentiation, tumor invasion and metastasis are expected to be suitable targets for transcription factor decoy.
Positron Emission Tomography in Cancer Research and Treatment
Authors: Mandelkern Mark , Raines Jonathan
Published: October 2014

Positron emission tomography (PET), the imaging of pharmaceuticals labeled with positronemitting radionuclides, is a rapidly growing modality for the diagnosis and management of cancer. PET yields high-quality images characterizing substrate metabolism, cellular proliferation, receptor density, and other parameters that can be used to identify cancer and evaluate its response to therapies. The technique mainly utilized in cancer management is FDG-PET, which exploits the abnormal glucose metabolism of cancer cells first characterized by Warburg. We discuss the principles of PET, the currently available instrumentation and radiopharmaceuticals, the efficacy of FDG-PET in the management of cancer, and the prospects for near-term advances in cancer using PET.
Dynamic Breast Tumor Oximetry: The Development of Prognostic Radiology
Authors: Song Yulin , Constantinescu Anca , Mason Ralph P.
Published: October 2014

A novel pre clinical approach to evaluating tumor oxygen dynamics was recently introduced (Am. J. Clin. Oncol. 24, 462–466 (2001)). FREDOM (Fluorocarbon Relaxometry using Echo planar imaging for Dynamic Oxygen Mapping) allows maps of tumor pO2 including 50 – 150 individual locations simultaneously to be produced with typical in plane resolution of 1.25 mm in 6.5 mins. The technique has been applied extensively in rat prostate tumors and is now demonstrated in the rat breast 13762NF adenocarcinoma. When anesthetized rats breathed 33% oxygen, mean baseline pO2 was in the range 17 ± 2 (se) torr to 74 ± 4 torr with mean value for nine tumors 46 ± 8 torr. However, small tumors (< 2.2 cm3) were significantly better oxygenated with mean pO2 = 63 ± 7 torr than large tumors (> 2.4 cm3) with mean pO2 24 ± 5 torr (p< 0.002). Switching the inhaled gas to oxygen or carbogen produced a significant and rapid increase in mean pO2 for both small and larger tumors (p< 0.05). Given the increasing evidence that tumor oxygenation is related to therapeutic outcome, we believe this approach to measuring tumor oxygen dynamics can be of value in predicting response to therapy, evaluating adjuvant interventions designed to modulate response to therapy, and in providing “Prognostic Radiology”.
Applications to Cancer Research of “Lab-on-a-chip” Devices Based on Dielectrophoresis (DEP)
Authors: Gambari Roberto , Borgatti Monica , Altomare Luigi , Manaresi Nicolo , Medoro Gianni , Romani Aldo , Tartagni Marco , Guerrieri Roberto
Published: October 2014

The recent development of advanced analytical and bioseparation methodologies based on microarrays and biosensors is one of the strategic objectives of the so-called post-genomic. In this field, the development of microfabricated devices could bring new opportunities in several application fields, such as predictive oncology, diagnostics and anti-tumor drug research. The so called “Laboratory-on-a-chip technology”, involving miniaturisation of analytical procedures, is expected to enable highly complex laboratory testing to move from the central laboratory into non-laboratory settings. The main advantages of Lab-on-a-chip devices are integration of multiple steps of different analytical procedures, large variety of applications, sub-microliter consumption of reagents and samples, and portability. One of the requirement for new generation Lab-on-a-chip devices is the possibility to be independent from additional preparative/analytical instruments. Ideally, Lab-on-a-chip devices should be able to perform with high efficiency and reproducibility both actuating and sensing procedures. In this review, we discuss applications of dielectrophoretic(DEP)-based Lab-on-a-chip devices to cancer research. The theory of dielectrophoresis as well as the description of several devices, based on spiral-shaped, parallel and arrayed electrodes are here presented. In addition, in this review we describe manipulation of cancer cells using advanced DEP-based Lab-on-a-chip devices in the absence of fluid flow and with the integration of both actuating and sensing procedures.