Radiation-induced malignant tumors of skin and their histogenesis

International Nuclear Information System (INIS)

Li Guomin; Chen Yunchi; Yang Yejing

1987-01-01

Seven cases of radiation-induced malignant tumors and 60 cases of chronic radiation damage of skin are reported. Severe hyperplasia, false epitheliomatoid hyperpiasia and atypical proliferation of epithelia and atypical proliferation of fibrohistocytes were the main changes found in chronic radiation damage of skin. The development of malignant tumors from chronic radiation damage of skin can be divided into 4 periods: necrotic and degenerative change period, benign proliferative period, atypical proliferative period and malignant change period. The incidence of hyperplastic changes of skin is related to the time elapse after irradiation and the integrated dose of radiation. The longer the duration after irradiation and the larger the integrated dose are, the higher will be the incidence of hyperplastic changes

Effect of skin tumor properties on laser penetration

CSIR Research Space (South Africa)

Karsten, AE

2009-06-01

Full Text Available Computer modeling can be a valuable tool to determine the absorption of laser light in different skin layers. For this study, the optical properties of three different skin tumors were used in the model to evaluate the effect on penetration depth...

Verification of skin dose according to the location of tumor in Tomotherapy

International Nuclear Information System (INIS)

Yoon, Bo Reum; Park, Su Yeon; Park, Byoung Suk; KIm, Jong Sik; Song, Ki Won

2014-01-01

To verify the skin dose in Tomotherapy-based radiation treatment according to the change in tumor locations, skin dose was measured by using Gafchromic EBT3 film and compared with the planned doses to find out the gap between them. In this study, to measure the skin dose, I'm RT Phantom(IBA Dosimetry, Germany) was utilized. After obtaining the 2.5 mm CT images, tumor locations and skin dose measuring points were set by using Pinnacle(ver 9.2, Philips Medical System, USA). The tumor location was decided to be 5 mm and 10 mm away from surface of the phantom and center. Considering the attenuation of a Tomo-couch, we ensured a symmetric placement between the ceiling and floor directions of the phantom. The measuring point of skin doses was set to have 3 mm and 5 mm thickness from the surface. Measurement was done 3 times. By employing TomoHD(TomoHD treatment system, Tomotherapy Inc., Madison, Wisconsin, USA), we devised Tomotherapy plans, measured 3 times by inserting Gafchromic EBT3 film into the phantom and compared the measurement with the skin dose treatment plans. The skin doses in the upper part of the phantom, when the tumor was located in the center, were found to be 7.53 cGy and 7.25 cGy in 5 mm and 3 mm respectively. If placed 5 mm away from the skin in the ceiling direction, doses were 18.06 cGy and 16.89 cGy; if 10 mm away, 20.37 cGy and 18.27 cGy, respectively. The skin doses in the lower part of the phantom, when the tumor was located in the center, recorded 8.82 cGy and 8.29 cGy in 5 mm and 3 mm, each; if located 5mm away from the lower part skin, 21.69 cGy and 19.78 cGy were respectively recorded; and if 10 mm away, 20.48 cGy and 19.57 cGy were recorded. If the tumor was placed in the center, skin doses were found to increase by 3.2-17.1% whereas if the tumor is 5 mm away from the ceiling part, the figure decreased to 2.8-9.0%. To the Tomo-couch direction, skin doses showed an average increase of 11% or over, compared to the planned treatment

Initiation-promotion skin carcinogenesis and immunological competence.

Science.gov (United States)

Curtis, G L; Stenbäck, F; Ryan, W L

1975-10-01

The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

Automated Estimation of Melanocytic Skin Tumor Thickness by Ultrasonic Radiofrequency Data.

Science.gov (United States)

Andrekute, Kristina; Valiukeviciene, Skaidra; Raisutis, Renaldas; Linkeviciute, Gintare; Makstiene, Jurgita; Kliunkiene, Renata

2016-05-01

High-frequency (>20-MHz) ultrasound (US) is a noninvasive preoperative tool for assessment of melanocytic skin tumor thickness. Ultrasonic melanocytic skin tumor thickness estimation is not always easy and is related to the experience of the clinician. In this article, we present an automated thickness measurement method based on time-frequency analysis of US radiofrequency signals. The study was performed on 52 thin (≤1-mm) melanocytic skin tumors (46 melanocytic nevi and 6 melanomas). Radiofrequency signals were obtained with a single-element focused transducer (fundamental frequency, 22 MHz; bandwidth, 12-28 MHz). The radiofrequency data were analyzed in the time-frequency domain to make the tumor boundaries more noticeable. The thicknesses of the tumors were evaluated by 3 different metrics: histologically measured Breslow thickness, manually measured US thickness, and automatically measured US thickness. The results showed a higher correlation coefficient between the automatically measured US thickness and Breslow thickness (r= 0.83; Pmeasured US thickness (r = 0.68; P measurement algorithm was 96.55%, and the specificity was 78.26% compared with histologic measurement. The sensitivity of the manually measured US thickness was 75.86%, and the specificity was 73.91%. The efficient automated tumor thickness measurement method developed could be used as a tool for preoperative assessment of melanocytic skin tumor thickness. © 2016 by the American Institute of Ultrasound in Medicine.

What is the microscopic tumor extent beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers?

Science.gov (United States)

Choo, Richard; Woo, Tony; Assaad, Dalal; Antonyshyn, Oleh; Barnes, Elizabeth A; McKenzie, David; Fialkov, Jeffrey; Breen, Dale; Mamedov, Alexander

2005-07-15

To quantify the microscopic tumor extension beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers. A prospective, single arm, study. Preoperatively, a radiation oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental marks in four directions from the delineated border. Under local anesthesia, the lesion was excised, and resection margins were assessed microscopically by frozen section. Once resection margins were clear, the microscopic tumor extent was calculated using the presurgical incremental markings as references. A potential relationship between the distance of microscopic tumor extension and other variables was analyzed. A total of 71 lesions in 64 consecutive patients, selected for surgical excision with frozen-section-assisted assessment of resection margins, were accrued. The distance of microscopic tumor extension beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.2 mm. A margin of 10 mm was required to provide a 95% chance of obtaining clear resection margins. The microscopic tumor extent was positively correlated with the size of gross lesion, but not with other variables. The distance of microscopic tumor extension beyond a gross nonmelanoma skin cancer was variable, with a mean of 5.2 mm. Such information is critical for the proper radiation planning of skin cancer therapy.

Expression of p63 and Cyclooxygenase-2 and Their Correlation in Skin Tumors

Institute of Scientific and Technical Information of China (English)

WU Yan; LIU Houjun; LI Jiawen

2007-01-01

To study the expression of p63 and cyclooxygenase-2 (cox-2) in skin tumors and evaluate the correlation between p63 and cox-2, the expressions of cox-2 and p63 were measured by streptavidin-peroxidase complex immunohistochemical technique in 17 cases of skin squamous cell carcinoma (SCC), 19 cases of Bowen's disease(Bowen), 11 cases of actinic keratosis(AK), 12 cases of seborreic keratosis(SK) and 13 specimens of normal skin. Our results showed that the expression of p63 in skin squamous cell carcinoma, Bowen's disease and actinic keratosis were significantly higher than that in seborreic keratosis, while the expression of p63 in seborreic keratosis was significantly higher than that in normal skin. The expression of cox-2 in skin squamous cell carcinoma,Bowen's disease and actinic keratosis were significantly higher than that in seborreic keratosis, while no statistical difference was noted in the expression of cox-2 between seborreic keratosis and normal skin. Cox-2 expression was positively correlated with the high p63 expression in malignant skin tumors. The increased expression of cox-2 and p63 may play an important role in the development of skin tumors and work synergetically in malignant skin tumors.

What is the microscopic tumor extent beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers?

International Nuclear Information System (INIS)

Choo, Richard; Woo, Tony; Assaad, Dalal; Antonyshyn, Oleh; Barnes, Elizabeth A.; McKenzie, David; Fialkov, Jeffrey; Breen, Dale; Mamedov, Alexander

2005-01-01

Purpose: To quantify the microscopic tumor extension beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers. Methods and Materials: A prospective, single arm, study. Preoperatively, a radiation oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental marks in four directions from the delineated border. Under local anesthesia, the lesion was excised, and resection margins were assessed microscopically by frozen section. Once resection margins were clear, the microscopic tumor extent was calculated using the presurgical incremental markings as references. A potential relationship between the distance of microscopic tumor extension and other variables was analyzed. Results: A total of 71 lesions in 64 consecutive patients, selected for surgical excision with frozen-section-assisted assessment of resection margins, were accrued. The distance of microscopic tumor extension beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.2 mm. A margin of 10 mm was required to provide a 95% chance of obtaining clear resection margins. The microscopic tumor extent was positively correlated with the size of gross lesion, but not with other variables. Conclusions: The distance of microscopic tumor extension beyond a gross nonmelanoma skin cancer was variable, with a mean of 5.2 mm. Such information is critical for the proper radiation planning of skin cancer therapy

Monoclonal antibodies reactive with common tumor antigens on UV-induced tumors also react with hyperplastic UV-irradiated skin

International Nuclear Information System (INIS)

Spellman, C.W.; Beauchamp, D.A.

1986-01-01

Most murine skin tumors induced by ultraviolet light (UVB, 280-340 nm) can be successfully transplanted only into syngeneic hosts that have received subcarcinogenic doses of UVB. The tumor susceptible state is long-lived and mediated by T suppressor cells that control effector responses against common antigens on UV-induced tumors. Because antigen specific suppression arises prior to the appearance of a tumor, questions arise about the source of the original antigen. They have previously reported transplantation studies indicating that UV-irradiated skin is antigenically cross-reactive with UV-induced tumors. They now report on flow cytometry analyses showing that a series of MoAb reactive with common antigens expressed by UV-induced tumors are also reactive on cells from UV-irradiated skin. Various antigens appear at different times in the UV irradiation scheme, and some persist while others are transient. They speculate that the common antigens detected may be the ones to which functional suppression is directed. If true, these results suggest that successful tumors need not escape host defenses to emerge. Rather, tumors may arise and grow progressively if they express antigens that cross-react with specificities to which the host has previously mounted a suppressive response

Palytoxin: exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis.

Science.gov (United States)

Wattenberg, Elizabeth V

2007-01-01

Palytoxin is a novel skin tumor promoter, which has been used to help probe the role of different types of signaling mechanisms in carcinogenesis. The multistage mouse skin model indicates that tumor promotion is an early, prolonged, and reversible phase of carcinogenesis. Understanding the molecular mechanisms underlying tumor promotion is therefore important for developing strategies to prevent and treat cancer. Naturally occurring tumor promoters that bind to specific cellular receptors have proven to be useful tools for investigating important biochemical events in multistage carcinogenesis. For example, the identification of protein kinase C as the receptor for the prototypical skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (also called phorbol 12-myristate 13-acetate, PMA) provided key evidence that tumor promotion involves the aberrant modulation of signaling cascades that govern cell fate and function. The subsequent discovery that palytoxin, a marine toxin isolated from zoanthids (genus Palythoa), is a potent skin tumor promoter yet does not activate protein kinase C indicated that investigating palytoxin action could help reveal new aspects of tumor promotion. Interestingly, the putative receptor for palytoxin is the Na(+),K(+)-ATPase. This review focuses on palytoxin-stimulated signaling and how palytoxin has been used to investigate alternate biochemical mechanisms by which important targets in carcinogenesis can be modulated.

Short-term biomarkers of tumor promotion in mouse skin treated with petroleum middle distillates.

Science.gov (United States)

Walborg, E F; DiGiovanni, J; Conti, C J; Slaga, T J; Freeman, J J; Steup, D R; Skisak, C M

1998-10-01

Topical application of certain petroleum middle distillates (PMD) to mice produces skin tumors after long latency, and initiation/promotion protocols indicate that this effect is associated with their tumor promoting activity. Since induction of sustained, potentiated epidermal hyperplasia is predictive of promoting activity, five compositionally distinct PMD [hydrodesulfurized kerosene (API 81-07); hydrodesulfurized PMD (API 81-10); odorless light petroleum hydrocarbons; severely hydrotreated light vacuum distillate (LVD); and lightly refined paraffinic oil (LRPO)] were assessed for their effects on epidermal hyperplasia. PMD were administered (2 x/week for 2 weeks) to skin of CD-1 mice. Four quantitative biomarkers of epidermal hyperplasia were evaluated: epidermal thickness, number of nucleated epidermal cells per unit length of basement membrane, labeling (BrdUrd) index of epidermal cells, and induction of epidermal ornithine decarboxylase (ODC) activity. As positive controls, 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-dodecane were utilized. PMD-induced skin irritation was evaluated visually and/or histopathologically. All five PMD produced dose-dependent, skin irritation and epidermal hyperplasia. On a weight basis the magnitude of the maximal PMD-induced effects was similar to that produced by n-dodecane, but > 1000-fold less than that produced by TPA. Epidermal hyperplasia and subacute skin irritancy produced by the five PMD were similar. Of the four short-term markers of tumor promotion assessed, labeling index and epidermal ODC activity were predictive of the relative promoting activities of those PMD for which tumorigenicity bioassay data are available, i.e., API 81-07 > API 81-10 > LRPO. An apparent discrepancy to the predictability of epidermal ODC activity occurred with LRPO:toluene [1:1 (v/v)]. This mixture is nontumorigenic, yet significantly induced epidermal ODC activity. This mixture, however, produced severe epidermal toxicity that

Tumor Suppressor Function of CYLD in Nonmelanoma Skin Cancer

Directory of Open Access Journals (Sweden)

K. C. Masoumi

2011-01-01

Full Text Available Ubiquitin and ubiquitin-related proteins posttranslationally modify substrates, and thereby alter the functions of their targets. The ubiquitination process is involved in various physiological responses, and dysregulation of components of the ubiquitin system has been linked to many diseases including skin cancer. The ubiquitin pathways activated among skin cancers are highly diverse and may reflect the various characteristics of the cancer type. Basal cell carcinoma and squamous cell carcinoma, the most common types of human skin cancer, are instances where the involvement of the deubiquitination enzyme CYLD has been recently highlighted. In basal cell carcinoma, the tumor suppressor protein CYLD is repressed at the transcriptional levels through hedgehog signaling pathway. Downregulation of CYLD in basal cell carcinoma was also shown to interfere with TrkC expression and signaling, thereby promoting cancer progression. By contrast, the level of CYLD is unchanged in squamous cell carcinoma, instead, catalytic inactivation of CYLD in the skin has been linked to the development of squamous cell carcinoma. This paper will focus on the current knowledge that links CYLD to nonmelanoma skin cancers and will explore recent insights regarding CYLD regulation of NF-κB and hedgehog signaling during the development and progression of these types of human tumors.

Induction of short-term biomarkers of tumor promotion in skin of CD-1 mice by petroleum middle distillates: preliminary observations.

Science.gov (United States)

Skisak, C; DiGiovanni, J; Conti, C J; Slaga, T J; Sharma, S; Sagartz, J W; Walborg, E F

1995-01-01

The induction of sustained epidermal hyperplasia in mouse skin has been shown to be a reliable predictor of tumor promoting activity for chemicals as diverse as phorbol esters, anthralins, n-dodecane and organic peroxides (DiGiovanni, 1992). The results contained herein demonstrate that API 81-07 and API 81-10, petroleum middle distillates that exhibit tumor promoting activity in mouse skin, induce epidermal hyperplasia and ODC activity. Other petroleum middle distillates (odorless light petroleum hydrocarbons, a light vacuum distillate, and a mineral seal oil) were also shown to share these activities. It should be emphasized that the relevance of these observations to human skin remains unresolved; however, the availability of these short-term biomarkers offers the opportunity to address the issue by performing comparative investigations on the effects of petroleum middle distillates on human skin xenografted to athymic (nude) mice. Such studies are being initiated.

The role of dermal irritation in the skin tumor promoting activity of petroleum middle distillates.

Science.gov (United States)

Nessel, C S; Freeman, J J; Forgash, R C; McKee, R H

1999-05-01

Petroleum middle distillates (PMDs), a class of hydrocarbons which boil between 350-700 degrees F, are tumor promoters in mouse skin. The promotional activity is produced under conditions that also result in local changes, including chronic irritation and epidermal hyperplasia. The present study was conducted by comparing equal weekly doses of irritating and minimally or nonirritating test materials, to assess whether tumor promotion was a secondary response to these effects. Four PMDs, C10-C14 normal paraffins (NP), lightly refined paraffinic oil (LRPO), Jet Fuel A (JF), and steam-cracked gas oil (SCGO), were evaluated. Test materials were applied undiluted (2x/week) or as 28.6% (7x/week) or 50% (4x/week) concentrations in mineral oil for 52 weeks following initiation with dimethylbenzanthracene (DMBA). When applied undiluted, all materials produced moderate irritation and significant increase in tumor incidence. When NP, LRPO, or JF were applied in mineral oil diluent, skin irritation was generally ameliorated and few, if any, tumors were produced. SCGO was irritating and produced a significant increase in tumor frequency when administered in mineral-oil diluent. These data indicate that the promotional activity of straight-run PMDs is likely related to chronic irritation at the application site and not to dose. Thus, when used appropriately in the absence of prolonged irritation, these materials should not present a tumorigenic hazard to humans.

Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients

International Nuclear Information System (INIS)

Dumaz, N.; Drougard, C.; Sarasin, A.; Daya-Grosjean, L.

1993-01-01

The UV component of sunlight is the major carcinogen involved in the etiology of skin cancers. The authors have studied the rare, hereditary syndrome xeroderma pigmentosum (XP), which is characterized by a very high incidence of cutaneous tumors on exposed skin at an early age, probably due to a deficiency in excision repair of UV-induced lesions. It is interesting to determine the UV mutation spectrum in XP skin tumors in order to correlate the absence of repair of specific DNA lesions and the initiation of skin tumors. The p53 gene is frequently mutated in human cancers and represents a good target for studying mutation spectra since there are >100 potential sites for phenotypic mutations. Using reverse transcription-PCR and single-strand conformation polymorphism to analyze >40 XP skin tumors (mainly basal and squamous cell carcinomas), the authors have found that 40% (17 out of 43) contained at least one point mutation on the p53 gene. All the mutations were located at dipyrimidine sites, essentially at CC sequences, which are hot spots for UV-induced DNA lesions. Sixty-one percent of these mutations were tandem CC → TT mutations considered to be unique to UV-induced lesions; these mutations are not observed in internal human tumors. All the mutations, except two, must be due to translesion synthesis of unrepaired dipyrimidine lesions left on the nontranscribed strand. These results show the existence of preferential repair of UV lesions [either pyrimidine dimers or pyrimidine-pyrimidone (6-4) photoproducts] on the transcribed strand in human tissues

Tumor Suppressor Function of CYLD in Non melanoma Skin Cancer

International Nuclear Information System (INIS)

Masoumi, K. C.; Hallgren, G. S.; Massoumi, R.

2011-01-01

Ubiquitin and ubiquitin-related proteins post translationally modify substrates, and thereby alter the functions of their targets. The ubiquitination process is involved in various physiological responses, and dysregulation of components of the ubiquitin system has been linked to many diseases including skin cancer. The ubiquitin pathways activated among skin cancers are highly diverse and may reflect the various characteristics of the cancer type. Basal cell carcinoma and squamous cell carcinoma, the most common types of human skin cancer, are instances where the involvement of the deubiquitination enzyme CYLD has been recently highlighted. In basal cell carcinoma, the tumor suppressor protein CYLD is repressed at the transcriptional levels through hedgehog signaling pathway. Downregulation of CYLD in basal cell carcinoma was also shown to interfere with TrkC expression and signaling, thereby promoting cancer progression. By contrast, the level of CYLD is unchanged in squamous cell carcinoma, instead, catalytic inactivation of CYLD in the skin has been linked to the development of squamous cell carcinoma. This paper will focus on the current knowledge that links CYLD to non melanoma skin cancers and will explore recent insights regarding CYLD regulation of NF-κB and hedgehog signaling during the development and progression of these types of human tumors.

[Initiation, promotion, initiation experiments with radon and cigarette smoke: Lung tumors in rats]. Progress report

International Nuclear Information System (INIS)

Moolgavkar, S.H.

1994-01-01

During the past several years, the authors have made considerable progress in modeling carcinogenesis in general, and in modeling radiation carcinogenesis, in particular. They present an overview of their progress in developing stochastic carcinogenesis models and applying them to experimental and epidemiologic data sets. Traditionally, cancer models have been used for the analysis of incidence (or prevalence) data in epidemiology and time to tumor data in experimental studies. The relevant quantities for the analysis of these data are the hazard function and the probability of tumor. The derivation of these quantities is briefly described here. More recently, the authors began to use these models for the analysis of data on intermediate lesions on the pathway to cancer. Such data are available in experimental carcinogenesis studies, in particular in initiation and promotion studies on the mouse skin and the rat liver. If however, quantitative information on intermediate lesions on the pathway to lung cancer were to be come available at some future date, the methods that they have developed for the analysis of initiation-promotion experiments could easily be applied to the analysis of these lesions. The mathematical derivations here are couched in terms of a particular two-mutation model of carcinogenesis. Extension to models postulating more than two mutations is not always straightforward

Loss of Endogenous Interleukin-12 Activates Survival Signals in Ultraviolet-Exposed Mouse Skin and Skin Tumors

Directory of Open Access Journals (Sweden)

Syed M. Meeran

2009-09-01

Full Text Available Interleukin-12 (IL-12-deficiency promotes photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Here, we report that long-term exposure to ultraviolet (UV radiation resulted in enhancement of the levels of cell survival kinases, such as phosphatidylinositol 3-kinase (PI3K, Akt (Ser473, p-ERK1/2, and p-p38 in the skin of IL-12p40 knockout (IL-12 KO mice compared with the skin of wild-type mice. UV-induced activation of nuclear factor-κB (NF-κB/p65 in the skin of IL-12 KO mice was also more prominent. The levels of NF-κB-targeted proteins, such as proliferating cell nuclear antigen (PCNA, cyclooxygenase-2, cyclin D1, and inducible nitric oxide synthase, were higher in the UV-exposed skin of IL-12 KO mice than the UV-exposed skin of wild types. In short-term UV irradiation experiments, subcutaneous treatment of IL-12 KO mice with recombinant IL-12 (rIL-12 or topical treatment with oridonin, an inhibitor of NF-κB, resulted in the inhibition of UV-induced increases in the levels of PCNA, cyclin D1, and NF-κB compared with non-rIL-12- or non-oridonin-treated IL-12 KO mice. UV-induced skin tumors of IL-12 KO mice had higher levels of PI3K, p-Akt (Ser473, p-ERK1/2, p-p38, NF-κB, and PCNA and fewer apoptotic cells than skin tumors of wild types. Together, these data suggest that the loss of endogenous IL-12 activates survival signals in UV-exposed skin and that may lead to the enhanced photocarcinogenesis in mice.

Initial assessment of tumor tracking with a gimbaled linac system in clinical circumstances: A patient simulation study

International Nuclear Information System (INIS)

Depuydt, Tom; Poels, Kenneth; Verellen, Dirk; Engels, Benedikt; Collen, Christine; Haverbeke, Chloe; Gevaert, Thierry; Buls, Nico; Van Gompel, Gert; Reynders, Truus; Duchateau, Michael; Tournel, Koen; Boussaer, Marlies; Steenbeke, Femke; Vandenbroucke, Frederik; De Ridder, Mark

2013-01-01

Purpose: To have an initial assessment of the Vero Dynamic Tracking workflow in clinical circumstances and quantify the performance of the tracking system, a simulation study was set up on 5 lung and liver patients. Methods and materials: The preparatory steps of a tumor tracking treatment, based on fiducial markers implanted in the tumor, were executed allowing pursuit of the tumor with the gimbaled linac and monitoring X-rays acquisition, however, without activating the 6 MV beam. Data were acquired on workflow time-efficiency, tracking accuracy and imaging exposure. Results: The average time between the patient entering the treatment room and the first treatment field was about 9 min. The time for building the correlation model was 3.2 min. Tracking errors of 0.55 and 0.95 mm (1σ) were observed in PAN/TILT direction and a 2D range of 3.08 mm. A skin dose was determined of 0.08 mGy/image, with a source-to-skin distance of 900 mm and kV exposure of 1 mAs. On average 1.8 mGy/min kV skin dose was observed for 1 Hz monitoring. Conclusion: The Vero tracking solution proved to be fully functional and showed performance comparable with other real-time tracking systems

Virtual microscopy: an evaluation of its validity and diagnostic performance in routine histologic diagnosis of skin tumors

DEFF Research Database (Denmark)

Nielsen, Patricia Switten; Lindebjerg, Jan; Rasmussen, Jan

2010-01-01

Digitization of histologic slides is associated with many advantages, and its use in routine diagnosis holds great promise. Nevertheless, few articles evaluate virtual microscopy in routine settings. This study is an evaluation of the validity and diagnostic performance of virtual microscopy...... in routine histologic diagnosis of skin tumors. Our aim is to investigate whether conventional microscopy of skin tumors can be replaced by virtual microscopy. Ninety-six skin tumors and skin-tumor-like changes were consecutively gathered over a 1-week period. Specimens were routinely processed, and digital...... slides were captured on Mirax Scan (Carl Zeiss MicroImaging, Göttingen, Germany). Four pathologists evaluated the 96 virtual slides and the associated 96 conventional slides twice with intermediate time intervals of at least 3 weeks. Virtual slides that caused difficulties were reevaluated to identify...

PRIMARY PREVENTION OF MALIGNANT SKIN TUMORS – PHOTOPROTECTION

Directory of Open Access Journals (Sweden)

Ana Benedičič - Pilih

2001-12-01

Full Text Available Background. The incidence of skin cancer is increasing in the world as well as in our country. Decades of research have increased the understanding of the ethiopathogenetic influences and risk factors for development of malignant skin tumors and stimulated efforts to promote their prevention. There are successes of prevention programs in some places in the world expressing with the reduction of mortality because of the cutaneous malignant melanoma. A primary prevention of a skin cancer attempts to change population knowledge, attitudes and beliefs about sunlight, leading to reduce of sunlight exposure.Conclusions. In this article we are discussing guidelines for photoprevention. The best approach to it is a reduction in the overall exposure to sunlight. The natural protection with the use of shade, clothing and hats is promoted as the best protection. Sunscreens are assumed as an important component of adjuvant photoprotection based on their convenience of use and also on their widespread promotion. While it has been argued that all tanning is a manifestation of skin injury, avoiding of artificial tanning devices is proposed also.

Sunscreens for delay of ultraviolet induction of skin tumors

International Nuclear Information System (INIS)

Wulf, H.C.; Poulsen, T.; Brodthagen, H.; Hou-Jensen, K.

1982-01-01

Sunscreens with different sun protection factors (SPFs) have been tested for their capability of delaying or preventing actinic damage and skin cancer development in groups of hairless, pigmented mice exposed to artificial ultraviolet (UV) light of increasing intensity. The dose delivered was less than or equal to 1 minimal erythema dose (MED) in the group of untreated mice, so that the mice to which sunscreens were applied never obtained a sunburn after UV exposure. The quality of UV light was similar to bright midday sun at a latitude of 56 degrees (city of Copenhagen). Tumorigenesis was demonstrated to be delayed corresponding to the SPF claimed by the manufacturer, but almost all of the UV-irradiated mice developed skin tumors. Histologic examination revealed actinic degeneration and tumors of squamous cell type with marked variation in differentiation. Metastases to lymph nodes and lungs were found in only 10%. Toxic reactions, such as eczematous-like skin reactions, dark coloring, and amyloidosis, were observed predominantly in the group treated with the sunscreen of highest SPF value. Long-term investigations seem to be necessary to unveil these problems--in particular, the specific SPF value, in sunscreens, that should be recommended to the public for prevention or delay of actinic damage and/or cancer development

FLUORESCENT DIAGNOSTICS OF MALIGNANT SKIN TUMORS WITH CHLORIN SERIES PHOTOSENSITIZERS

Directory of Open Access Journals (Sweden)

E. V. Yaroslavtseva-Isaeva

2018-01-01

Full Text Available The article shows possibilities in fluorescence imaging of malignant skin tumors with chlorin series photosensitizers (PS photolon and fotoditazin. The regularities of photosensitizer accumulation from the data of local fluorescence spectroscopy depending on the PS and its dose, the clinical picture and the histological form of the malignant skin neoplasm is investigated. It is shown that the level and selectivity of PS accumulation in the tumor focus depends on the PS dose. In studies on 10 patients with basal cell skin cancer after the introduction of fotoditazin at a dose less than 1 mg/kg, fluorescent contrast between tumor and healthy tissue varied between 1.3 and 9.5, the average was 2.8±0.3; for patients who had the administered fotoditazin dose of 1 mg/kg, fluorescent contrast was 2.9±0.4, varying from 1.4 to 5. In a study with 127 patients after the introduction of photolon in the dose of 0.7-1 mg/kg, the average value of the fluorescence intensity in relative units in the intact skin was 6.9±0.3 (min 4.6, max 12.2, at a dose of 1.1 to 1.4 mg/kg – 8.0±0.3 (min 4.6, max 12.5, at a dose of 1.5-2 mg/kg – 9.9±0.7 (min 5.7, max 20.3. It is also shown that fluorescence intensity of malignant neoplasm of the skin with the same dose of the photosensitizer depends on the neoplasm’s clinical and histological forms. So, 3 hours after the introduction of photolon at a dose of 1.3 mg/kg the average fluorescent contrast in the surface type of skin cancer was 2.7±0.5, in the nodal form – 2.3±0.2, in erosive-ulcerative form – 3.6±0.3. In patients with nodular form of squamous skin cancer after the introduction of photolon at a dose of 1.3 mg/kg fluorescent contrast was significantly higher (p<0.05 (average of 2.8±0.2 than in the nodular form of basal cell carcinoma after the introduction of photolon at the same dose (average of 2.1±0.2.

Neuroendocrine tumor of the skin of head and neck

Directory of Open Access Journals (Sweden)

Stošić Srboljub

2005-01-01

Full Text Available Background. Merkel cell carcinom is a rare neuroendrocine tumor of skin which manifests it self through aggressive growth and early regional metastasis. It develops mainly in older population. Locally, the tumor spreads intracutaneously. Case report. We showed two cases (females of 89 and 70 years old hospitalized within the last two years. The first patient was treated surgically three times. After the surgery, the patient was treated with radio therapy, and died 3 years from the beginning of the treatment. The second patient with this neuroendocrine tumor with the high malignancy potential and huge regional metastasis, was treated surgically, and died a month and a half after the operation. Conclusion. These two cases confirmed the aggressive and recidivant growth of this tumor with the difficult pathologic investigation, and the extremely bad prognosis inspite of the treatment.

Importance of tumor size and repopulation for radiocurability of skin cancer

International Nuclear Information System (INIS)

Maciejewski, B.A.; Zajusz, A.; Lange, D.

1993-01-01

Data on 946 skin cancers treated by radiation were used to estimate the importance of repopulation. Six different treatment regimes were used, from a single dose to 74 Gy given in 47 fractions. High local control of the small skin cancers (L 1 cm) was independent of dose fractionation. For large tumors, only 74 Gy in 47 fractions was the optimal treatment. Time factor analysis showed a steep increase in the NTD50 values between day 28 and 65 of treatment. This implies that tumor clonogen repopulation starts around 4 weeks of treatment. The present results show a three-component dose-response curve instead of the two-component curves which were found for head and neck and bladder cancer. (author) 1 tab., 2 figs., 15 refs

"Inhibitory Effect of Tannic Acid from Nutgall on Iron-Dextran Augmented 7,12-Dimethyl Benz(AAnthracene-Initiated and Croton Oil-Promoted Skin Carcinogenesis "

Directory of Open Access Journals (Sweden)

Abbas Delazar

2003-08-01

Full Text Available Tannic acid (TA is naturally occurring polyphenols present in fruits and vegetables. In this study, inhibition of the carcinogenic potential of croton oil in normal and iron overloaded mice skin by TA is reported. Albino Swiss mice were given iron-dextran for two weeks and were pretreated with a single topical application of tannic acid. After one hour tumors were initiated by a single dose of 7,12- dimethylbenz(aanthracene (DMBA the promoting agent croton oil was applied twice a week for 30 weeks. The appearance, number and percent tumor incidences were recorded. When compared to control groups, the pretreated groups showed a significant high inhibition of tumors incidences. Biochemical studies in mice skin tissues were based on the measurement of lipid peroxidation (LPO. TA diminished cutaneous LPO level in mice skin as compared to the untreated groups. This study showed that TA inhibits the augmentation potentials of croton oil and iron dextran significantly. A depletion in LPO levels in TA pretreated groups indicates that excessive generated oxidants in the mice skin tissues may be quenched by TA because of chelation of redox active iron and its faster elimination from the body. It is supposed that inhibition of iron mediated oxidative stress by TA may be responsible for diminishment of cutaneous tumorigenesis.

Preventive effect of chemical peeling on ultraviolet induced skin tumor formation.

Science.gov (United States)

Abdel-Daim, Mohamed; Funasaka, Yoko; Kamo, Tsuneyoshi; Ooe, Masahiko; Matsunaka, Hiroshi; Yanagita, Emmy; Itoh, Tomoo; Nishigori, Chikako

2010-10-01

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

Science.gov (United States)

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Studies on reconstruction of large skin defects following mammary tumor excision in dogs

Directory of Open Access Journals (Sweden)

Sabarish Babu Malli Sadhasivan

2017-12-01

Full Text Available Aim: The main objective of the study was to describe the use of skin fold advancement flaps (SFAFs and other reconstructive techniques for closure of large skin defects following mammary tumor excision in dogs. Materials and Methods: Twelve dogs underwent reconstruction of large ventral skin defects following mammary tumor excision with wide margins. Skin fold flaps (flank fold flap and elbow fold flap were elevated from the flank and elbow region, respectively, and transposed and sutured onto the large ventral skin defect following mastectomy in all the dogs. In addition to the skin fold flaps, other reconstructive techniques such as undermining, walking sutures, and tension-relieving suture techniques were followed during surgery in the closure of large skin defects without skin tension and compromising limb mobility. The skin flap viability was assessed subjectively by gross observation of the flap such as color, temperature, capillary perfusion, and cosmetic appearance, and scoring (1-4 was done. Tissue samples were collected from a surgical site on days 3, 6, and 12 post-operatively for histopathological evaluation and healing status of the skin flap. Results: All the surgical wounds healed primarily, without any major complications and the skin flap remained healthy throughout the healing process post-operatively. Distal flap necrosis was noticed in one case and necrosis of skin flap between two suture lines was noticed in another case in which the necrotized distal portion healed by secondary intention after 7 days. The mean survival of subdermal plexus flap in the above cases was 98% which was a subjective evaluation based on surface area of the skin defect measured by Image 'J software and the flap dimensions. The average healing of skin flap in days was 14.91±0.86. Conclusion: The SFAFs along with other reconstructive techniques help in the reconstruction of large ventral skin defects following mastectomy in dogs without much

Ability of PABA to protect mammalian skin from ultraviolet light-induced skin tumors and actinic damage

International Nuclear Information System (INIS)

Snyder, D.S.; May, M.

1975-01-01

Application of 5% para-aminobenzoic acid (PABA) to hairless mice one hour prior to ultraviolet light (UVL) irradiation will almost totally protect these animals from developing tumors induced by chronic exposure to UVL in the 290 to 320 nm range in conjunction with a chemical carcinogen. Mice exposed to UVL and not protected by PABA developed primarily squamous cell carcinomas. Two months after cessation of chronic UVL exposure, the non-PABA-treated irradiated mouse skin appeared thickened, yellow, and wrinkled while showing elevated DNA synthesis, hyperplasia, hypergranulosis, and increased amounts of elastotic material. The PABA-treated skin was grossly normal

Skin tumor area extraction using an improved dynamic programming approach.

Science.gov (United States)

Abbas, Qaisar; Celebi, M E; Fondón García, Irene

2012-05-01

Border (B) description of melanoma and other pigmented skin lesions is one of the most important tasks for the clinical diagnosis of dermoscopy images using the ABCD rule. For an accurate description of the border, there must be an effective skin tumor area extraction (STAE) method. However, this task is complicated due to uneven illumination, artifacts present in the lesions and smooth areas or fuzzy borders of the desired regions. In this paper, a novel STAE algorithm based on improved dynamic programming (IDP) is presented. The STAE technique consists of the following four steps: color space transform, pre-processing, rough tumor area detection and refinement of the segmented area. The procedure is performed in the CIE L(*) a(*) b(*) color space, which is approximately uniform and is therefore related to dermatologist's perception. After pre-processing the skin lesions to reduce artifacts, the DP algorithm is improved by introducing a local cost function, which is based on color and texture weights. The STAE method is tested on a total of 100 dermoscopic images. In order to compare the performance of STAE with other state-of-the-art algorithms, various statistical measures based on dermatologist-drawn borders are utilized as a ground truth. The proposed method outperforms the others with a sensitivity of 96.64%, a specificity of 98.14% and an error probability of 5.23%. The results demonstrate that this STAE method by IDP is an effective solution when compared with other state-of-the-art segmentation techniques. The proposed method can accurately extract tumor borders in dermoscopy images. © 2011 John Wiley & Sons A/S.

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Directory of Open Access Journals (Sweden)

Dapkute D

2017-11-01

Full Text Available Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Latvia, Riga, Latvia; 4Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania Purpose: Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs.Materials and methods: Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used.Results: QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the

Controversial role of mast cells in skin cancers.

Science.gov (United States)

Varricchi, Gilda; Galdiero, Maria R; Marone, Giancarlo; Granata, Francescopaolo; Borriello, Francesco; Marone, Gianni

2017-01-01

Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumor initiation and progression. The stromal microenvironment can promote tumor development. Mast cells, widely distributed throughout all tissues, are a stromal component of many solid and haematologic tumors. Mast cells can be found in human and mouse models of skin cancers such as melanoma, basal and squamous cell carcinomas, primary cutaneous lymphomas, haemangiomas and Merkel cell carcinoma. However, human and animal studies addressing potential functions of mast cells and their mediators in skin cancers have provided conflicting results. In several studies, mast cells play a pro-tumorigenic role, whereas in others, they play an anti-tumorigenic role. Other studies have failed to demonstrate a clear role for tumor-associated mast cells. Many unanswered questions need to be addressed before we understand whether tumor-associated mast cells are adversaries, allies or simply innocent bystanders in different types and subtypes of skin cancers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of low-energy laser radiation on normal skin and certain tumor tissues

Energy Technology Data Exchange (ETDEWEB)

Pletnev, S.D.; Karpenko, O.M.

For some years, the authors' Institute has studied the influence of various types of low-energy laser radiation on normal tissue and the growth of tumors. Radiation at 3 and 30 J/cm/sup 2/ causes an increase in biological activity of various cell elements, manifested as an increase in mitotic activity of the cells in the basal layer of the epidermis, conglomeration of chromatin in the cell nuclei and an increase in degranulation of fat cells in the process of their migration to the reticular layer. Also noted was an increase in content of fibroblastic and lymphohistocytic elements in the dermis, as well as an increase in collagenization of connective tissue. It was found that irradiation of the skin by helium-neon, cadmium-helium and nitrogen lasers before and after grafting of the cells of various tumors modifies the course of the tumor process. This effect is apparently related to the fact that systematic irradiation results in changes creating a favorable background for survival and proliferation of tumor cells in the skin tissue medium. The changes facilitate an increase in survival and growth of both pigmented and nonpigmented tumors. Low power radiation stimulates the activity of the cells or cell structures; medium power stimulates their activity; high power suppresses activity.

Ionizing radiation in tumor promotion and progression

International Nuclear Information System (INIS)

Mitchel, R.E.J.

1990-08-01

Chronic exposure to beta radiation has been tested as a tumor promoting or progressing agent. The dorsal skins of groups of 25 female SENCAR mice were chemically initiated with a single exposure to DMBA, and chronic exposure to strontium-90/yttrium-90 beta radiation was tested as a stage 1, stage 2 or complete skin tumor promoter. Exposure of initiated mice to 0.5 gray twice a week for 13 weeks produced no papillomas, indicating no action as a complete promoter. Another similar group of animals was chemically promoted through stage 1 (with TPA) followed by 0.5 gray of beta radiation twice a week for 13 weeks. Again no papillomas developed indicating no action of chronic radiation as a stage 2 tumor promoter. The same radiation exposure protocol in another DMBA initiated group receiving both stage 1 and 2 chemical promotion resulted in a decrease in papilloma frequency, compared to the control group receiving no beta irradiation, indicating a tumor preventing effect of radiation at stage 2 promotion, probably by killing initiated cells. Chronic beta radiation was tested three different ways as a stage 1 tumor promoter. When compared to the appropriate control, beta radiation given after initiation as a stage 1 promoter (0.5 gray twice a week for 13 weeks), after initiation and along with a known stage 1 chemical promoter (1.0 gray twice a week for 2 weeks), or prior to initiation as a stage 1 promoter (0.5 gray twice a week for 4 weeks), each time showed a weak (∼ 15% stimulation) but statistically significant (p<0.01) ability to act as a stage 1 promoter. When tested as a tumor progressing agent delivered to pre-existing papillomas, beta radiation (0.5 gray twice a week for 13 weeks) increased carcinoma frequency from 0.52 to 0.68 carcinoma/animal, but this increase was not statistically significant at the 95% confidence level. We conclude that in the addition to the known initiating, progressing and complete carcinogenic action of acute exposures to ionizing

Clear cell hidradenocarcinoma of the breast: a very rare breast skin tumor.

Science.gov (United States)

Mezzabotta, Maurizio; Declich, Paolo; Cardarelli, Mery; Bellone, Stefano; Pacilli, Paolo; Riggio, Eliana; Pallino, Antonio

2012-01-01

Hidradenocarcinoma is an uncommon malignant intradermal tumor of sweat gland origin with a predilection for the face and extremities. It is encountered equally in males and females, usually in the second half of life. These tumors tend to be locally aggressive. In our case, the tumor was located relatively superficially but without any apparent connection to the overlying skin. The typical disease course includes local and sometimes multiple recurrences, and some patients develop regional lymph node and distant metastases. These type of tumors in the parenchyma of the breast are extremely rare. We report a case of hidradenocarcinoma in a 77-year-old woman who presented with a palpable inflammatory nodule in the right breast.

Salient points in reconstruction of nasal skin after tumor ablation with local flaps

Directory of Open Access Journals (Sweden)

Ali Ebrahimi

2016-01-01

Full Text Available Objective: A variety of nasal skin reconstruction methods are available to meet the esthetic patient's needs. In this article, we review some of modifications of these procedures and share our experience in reconstruction of different parts of the nasal skin following skin tumor ablation. Patients and Methods : From January 2010 to January 2014, 171 patients underwent nasal skin reconstruction after excising cancerous lesions of the involved nasal skin. The patient's history, pre- and post-operation photographs, and the surgery data were collected and assessed. Demographic data related to the type of cancer, defect size and location, type of reconstruction were collected. Results: A variety of local flaps were used based on location and defect features. Nearly all flaps healed primarily without postsurgical significant complications. Conclusion: According to the results and the outcomes of the operations, we concluded that a certain flaps are more effective than others in nasal skin reconstruction. Local flap reconstruction of the nose has good esthetic result with low complication rate.

Analysis of 3D OCT images for diagnosis of skin tumors

Science.gov (United States)

Raupov, Dmitry S.; Myakinin, Oleg O.; Bratchenko, Ivan A.; Zakharov, Valery P.; Khramov, Alexander G.

2018-04-01

Skin cancer is one of the fastest growing type of cancer. It represents the most commonly diagnosed malignancy, surpassing lung, breast, colorectal and prostate cancer. So, diagnostics for different types of skin cancer on early stages is a very high challenge for medicine industry. New optical imaging techniques have been developed in order to improve diagnostics precision. Optical coherence tomography (OCT) is based on low-coherence interferometry to detect the intensity of backscattered infrared light from biological tissues by measuring the optical path length. OCT provides the advantage of real-time, in vivo, low-cost imaging of suspicious lesions without having to proceed directly to a tissue biopsy. The post-processing techniques can be used for improving the precision of diagnostics and providing solutions to overcome limitations for OCT. Image processing can include noise filtration and evaluation of textural, geometric, morphological, spectral, statistic and other features. The main idea of this investigation is using information received from multiple analyze on 2D- and 3D-OCT images for skin tumors differentiating. At first, we tested the computer algorithm on OCT data hypercubes and separated B- and C-scans. Combination of 2D and 3D data give us an opportunity to receive common information about tumor (geometric and morphological characteristics) and use more powerful algorithms for features evaluation (fractal and textural) on these separated scans. These groups of features provide closer connection to classical wide-used ABCDE criteria (Asymmetry, Border irregularity, Color, Diameter, Evolution). We used a set of features consisting of fractal dimension, Haralick's, Gabor's, Tamura's, Markov random fields, geometric features and many others. We could note about good results on the test sets in differentiation between BCC and Nevus, MM and Healthy Skin. We received dividing MM from Healthy Skin with sensitivity more 90% and specificity more 92% (168 B

A case grafted with polyglycolic acid sheets and fibrin glue for protection after temporary resection of a metastatic cervical skin tumor.

Science.gov (United States)

Matsuzuka, Takashi; Suzuki, Masahiro; Ikeda, Masakazu; Sato, Kaoru; Fujimoto, Junko; Hosaka, Rumi; Tanji, Yuko; Soeda, Shu; Murono, Shigeyuki

2018-04-01

The aim of this case report was to evaluate the usefulness of a grafting with polyglycolic acid sheet and a fibrin glue spray (PGA sheet grafting) after resection of a cervical skin tumor. A 61-year-old woman presented with left cervical skin tumor resistance to chemo-radiotherapy. She had been undergoing multimodal therapy for ovarian serous papillary adenocarcinoma for the previous six years. Although she had a poor general condition and a cervical skin tumor of 9cm in diameter, which was painful and easy bleeding, had offensive smell, she hoped to return to her job. Under local anesthesia, resection was performed, and PGA sheet grafting were used to shield the skin defect. After resection, she was relieved from pain, and could stay home without daily wound treatment. One and half months after resection, the wound was almost epithelialized. The PGA sheets consist of soft, elastic, nonwoven fabric made of PGA. In recent years, PGA sheet grafting has been widely used in the reconstruction and was chosen to shield the skin defect for this case. PGA sheet grafting after resection of cervical skin tumor can be an acceptable method for palliative care to relieve pain, bleeding, offensive smell, and ugly appearance. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting sarcoma tumor-initiating cells through differentiation therapy

Directory of Open Access Journals (Sweden)

Dan Han

2017-05-01

Full Text Available Human leukocyte antigen class I (HLA-I down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.

Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice

Energy Technology Data Exchange (ETDEWEB)

Vaid, Mudit; Singh, Tripti; Prasad, Ram [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Katiyar, Santosh K., E-mail: skatiyar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Birmingham Veterans Affairs Medical Center, Birmingham, AL 35294 (United States)

2014-01-01

Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180 mJ/cm{sup 2}) three times a week for 24 weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P < 0.01–0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression of UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (P < 0.01), and PGE{sub 2} receptors, and activation of NF-κB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-α (P < 0.01), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser{sup 473} in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. - Highlights: • Consumption of high-fat diet increases UVB-induced skin tumor development in mice. • Intake of high-fat diet stimulates progression of UV-induced papilloma to carcinoma. • Intake of high-fat diet enhances inflammation in UV-exposed skin • Regular

Health initiatives for the prevention of skin cancer.

Science.gov (United States)

Greinert, Rüdiger; Breitbart, Eckhard W; Mohr, Peter; Volkmer, Beate

2014-01-01

Skin cancer is the most frequent type of cancer in white population worldwide. However, because the most prominent risk factor-solar UV-radiation and/or artificial UV from sunbeds-is known, skin cancer is highly preventable be primary prevention. This prevention needs, that the public is informed by simple and balanced messages about the possible harms and benefits of UV-exposure and how a person should behave under certain conditions of UV-exposure. For this purpose information and recommendations for the public must be age- and target-group specific to cover all periods of life and to reach all sub-groups of a population, continuously. There is a need that political institutions together with Health Institutions and Societies (e.g., European Commission, WHO, EUROSKIN, ICNIRP, etc.), which are responsible for primary prevention of skin cancer, find a common language to inform the public, in order not to confuse it. This is especially important in connection with the ongoing Vitamin D debate, where possible positive effects of UV have to be balanced with the well known skin cancer risk of UV. A continuously ongoing evaluation of interventions and programs in primary prevention is a pre-requisite to assess the effectiveness of strategies. There is surely no "no message fits all" approach, but balanced information in health initiatives for prevention of skin cancer, which use evidence-base strategies, will further be needed in the future to reduce the incidence, morbidity and mortality skin cancer.

UV Radiation and the Skin

Directory of Open Access Journals (Sweden)

Timothy Scott

2013-06-01

Full Text Available UV radiation (UV is classified as a “complete carcinogen” because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance.

Mesenchymal stem cells cancel azoxymethane-induced tumor initiation.

Science.gov (United States)

Nasuno, Masanao; Arimura, Yoshiaki; Nagaishi, Kanna; Isshiki, Hiroyuki; Onodera, Kei; Nakagaki, Suguru; Watanabe, Shuhei; Idogawa, Masashi; Yamashita, Kentaro; Naishiro, Yasuyoshi; Adachi, Yasushi; Suzuki, Hiromu; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

2014-04-01

The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our goal was to determine whether exogenous MSCs possess intrinsic antineoplastic or proneoplastic properties in azoxymethane (AOM)-induced carcinogenesis. Three in vivo models were studied: an AOM/dextran sulfate sodium colitis-associated carcinoma model, an aberrant crypt foci model, and a model to assess the acute apoptotic response of a genotoxic carcinogen (AARGC). We also performed in vitro coculture experiments. As a result, we found that MSCs partially canceled AOM-induced tumor initiation but not tumor promotion. Moreover, MSCs inhibited the AARGC in colonic epithelial cells because of the removal of O(6)-methylguanine (O(6) MeG) adducts through O(6) MeG-DNA methyltransferase activation. Furthermore, MSCs broadly affected the cell-cycle machinery, potentially leading to G1 arrest in vivo. Coculture of IEC-6 rat intestinal cells with MSCs not only arrested the cell cycle at the G1 phase, but also induced apoptosis. The anti-carcinogenetic properties of MSCs in vitro required transforming growth factor (TGF)-β signaling because such properties were completely abrogated by absorption of TGF-β under indirect coculture conditions. MSCs inhibited AOM-induced tumor initiation by preventing the initiating cells from sustaining DNA insults and subsequently inducing G1 arrest in the initiated cells that escaped from the AARGC. Furthermore, tumor initiation perturbed by MSCs might potentially dysregulate WNT and TGF-β-Smad signaling pathways in subsequent tumorigenesis. Obtaining a better understanding of MSC functions in colon carcinogenesis is essential before commencing the broader clinical application of promising MSC-based therapies for cancer-prone patients with inflammatory bowel disease. © AlphaMed Press.

Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

Directory of Open Access Journals (Sweden)

Ganapati V Hegde

Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

Usefulness of V-Y Advancement Flap for Defects after Skin Tumor Excision

Directory of Open Access Journals (Sweden)

Ki Hyun Kwon

2012-11-01

Full Text Available BackgroundAfter skin tumor excision on the face, extremities, or trunk, the choice of treatment for a skin defect is highly variable. Many surgeons prefer to use a local flap rather than a skin graft or free flap for small- or moderately-sized circular defects. We have used unilateral or bilateral V-Y advancement flaps, especially on the face. Here we evaluated the functional and aesthetic results of this technique.MethodsAll of the patients were pathologically diagnosed with squamous cell carcinoma (SCC, basal cell carcinoma (BCC, or malignant melanoma or premalignant lesion (Bowen's disease. Thirty-two patients underwent V-Y advancement flap repair (11 unilateral and 21 bilateral from January 2007 to June 2011. We analyzed the patients' age and satisfaction, and location and size of defect. The patients were followed up for 6 months or more.ResultsThere were 22 women and 10 men. The ages ranged from 47 to 93 years with a mean age of 66 years. The causes were SCC in 15 cases, BCC in 13 cases, malignant melanoma in 1 case, Bowen's disease in 2 cases, and another cause in 1 case. The tumor locations were the face in 28 patients, and the scalp, upper limb, and flank each in one patient. All of the flaps survived and the aesthetic results were good. Postoperative recovery was usually rapid, and no complication or tumor recurrence was observed.ConclusionsThe V-Y advancement flap is often used not only for facial circular defects but also for defects of the trunk and extremities. Its advantages are less scarring and superior aesthetic results as compared with other local flap methods, because of less scarification of adjacent tissue and because it is an easy surgical technique.

Radiophosphorus (32P)-test on precancerosis and malignant tumors of the skin

International Nuclear Information System (INIS)

Biersack, H.J.; Rodermund, O.E.; Meurin, G.; Winkler, C.; Bonn Univ.

1976-01-01

In 21 patients with a variety of skin tumors (squamous cell carcinomas, malignant melanomas, basal cell epitheliomas and mycosis fungoides) or precancerous lesions (Bowen's disease, actinic keratosis, junctional nevus cell nevus) the radioactive phosphorus uptake test demonstrates a sign ficantly increased concentration of P 32 in those tumors. There were no false negative tests. The possibility of differentiation of malignant melanoma from benign nevus cell nevus and the early recognition of cutaneous metastases is described. Furthermore recurrence of previously irradiated or excised basal cell epitheliomas can be detected without a biopsy. No hematological side-effects were observed. (orig.) [de

Detection of new MHC mutations in mice by skin grafting, tumor transplantation and monoclonal antibodies: a comparison

International Nuclear Information System (INIS)

Egorov, I.K.; Egorov, O.S.

1988-01-01

Two mechanisms of major histocompatibility complex (MHC) mutations have been described in mice: gene conversion and homologous but unequal recombination. However, the knowledge of mutations in MHC is incomplete because studies have been limited almost exclusively to two haplotypes, H-2/sup b/ and H-2/sup d/, while hundreds of haplotypes exist in nature; it has been biased by the use of only one procedure of screening for mutation, skin grafting. The authors used three procedures to screen for MHC mutations: (1) conventional techniques of skin grafting, (2) syngeneic tumor transplantation and (3) typing with monoclonal anti-MHC antibodies (mAbs) and complement. The faster technique of tumor transplantation detected mutants similar to those discovered by skin grafting technique. Screening with mAbs allowed us to detect both mutants that are capable of rejecting standard skin grafts and those that are silent in skin grafting tests, and which therefore resulted in a higher apparent mutation frequency. Two mutants of the H-2/sup a/ haplotype were found that carry concomitant class I and class II antigenic alterations. Both MHC mutants silent in skin grafting tests and mutants carrying concomitant class I and class II alterations have never been studied before and are expected to reveal new mechanisms of generating MHC mutations. 1-Ethyl-1-nitrosourea (ENU) failed to induce de novo MHC mutations in our skin grafting series

Imaging Reporters for Proteasome Activity Identify Tumor- and Metastasis-Initiating Cells

Directory of Open Access Journals (Sweden)

Amanda C. Stacer

2015-08-01

Full Text Available Tumor-initiating cells, also designated as cancer stem cells, are proposed to constitute a subpopulation of malignant cells central to tumorigenesis, metastasis, and treatment resistance. We analyzed the activity of the proteasome, the primary organelle for targeted protein degradation, as a marker of tumor- and metastasis-initiating cells. Using human and mouse breast cancer cells expressing a validated fluorescent reporter, we found a small subpopulation of cells with low proteasome activity that divided asymmetrically to produce daughter cells with low or high proteasome activity. Breast cancer cells with low proteasome activity had greater local tumor formation and metastasis in immunocompromised and immunocompetent mice. To allow flexible labeling of cells, we also developed a new proteasome substrate based on HaloTag technology. Patient-derived glioblastoma cells with low proteasome activity measured by the HaloTag reporter show key phenotypes associated with tumor-initiating cells, including expression of a stem cell transcription factor, reconstitution of the original starting population, and enhanced neurosphere formation. We also show that patient-derived glioblastoma cells with low proteasome activity have higher frequency of tumor formation in mouse xenografts. These studies support proteasome function as a tool to investigate tumor- and metastasis-initiating cancer cells and a potential biomarker for outcomes in patients with several different cancers.

Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

Science.gov (United States)

Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

2007-04-01

Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

Laser photoradiation therapy in the treatment of malignant tumors

International Nuclear Information System (INIS)

Tomio, L.; Corti, L.; Polico, C.

1987-01-01

Photoradiation theraphy or, as more recently defined, photodynamic theraphy (PDT) has been effective in the treatment of several kinds of cancers, above all the skin, lung, esophagus and bladder. It is based on the preferential retention by tumor and photosensitizing properties of certains porphyrins.It has been initiated to investigate this technique experimentally in 1978 and clinically in september 1982, with report of the initial results in 38 patients in 1985. In this paper the more recent experience of PDT in 18 patients affected by different tumors and treated with a new double argon-dye laser system is described. These tumors included 8 carcinomas of the esophagus, 5 basal cell skin cancers, 2 carcinomas of the lung, 2 squamous cell carcinomas of the oral cavity and 1 early gastric cancer. Clinical results and technical problems of PDT are discussed

A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

International Nuclear Information System (INIS)

Dinkova-Kostova, Albena T.; Jenkins, Stephanie N.; Wehage, Scott L.; Huso, David L.; Benedict, Andrea L.; Stephenson, Katherine K.; Fahey, Jed W.; Liu Hua; Liby, Karen T.; Honda, Tadashi; Gribble, Gordon W.; Sporn, Michael B.; Talalay, Paul

2008-01-01

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm 2 /session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality

Grape seed proanthocyanidins reactivate silenced tumor suppressor genes in human skin cancer cells by targeting epigenetic regulators

International Nuclear Information System (INIS)

Vaid, Mudit; Prasad, Ram; Singh, Tripti; Jones, Virginia; Katiyar, Santosh K.

2012-01-01

Grape seed proanthocyanidins (GSPs) have been shown to have anti-skin carcinogenic effects in in vitro and in vivo models. However, the precise epigenetic molecular mechanisms remain unexplored. This study was designed to investigate whether GSPs reactivate silenced tumor suppressor genes following epigenetic modifications in skin cancer cells. For this purpose, A431 and SCC13 human squamous cell carcinoma cell lines were used as in vitro models. The effects of GSPs on DNA methylation, histone modifications and tumor suppressor gene expressions were studied in these cell lines using enzyme activity assays, western blotting, dot-blot analysis and real-time polymerase chain reaction (RT-PCR). We found that treatment of A431 and SCC13 cells with GSPs decreased the levels of: (i) global DNA methylation, (ii) 5-methylcytosine, (iii) DNA methyltransferase (DNMT) activity and (iv) messenger RNA (mRNA) and protein levels of DNMT1, DNMT3a and DNMT3b in these cells. Similar effects were noted when these cancer cells were treated identically with 5-aza-2′-deoxycytidine, an inhibitor of DNA methylation. GSPs decreased histone deacetylase activity, increased levels of acetylated lysines 9 and 14 on histone H3 (H3-Lys 9 and 14) and acetylated lysines 5, 12 and 16 on histone H4, and reduced the levels of methylated H3-Lys 9. Further, GSP treatment resulted in re-expression of the mRNA and proteins of silenced tumor suppressor genes, RASSF1A, p16 INK4a and Cip1/p21. Together, this study provides a new insight into the epigenetic mechanisms of GSPs and may have significant implications for epigenetic therapy in the treatment/prevention of skin cancers in humans. -- Highlights: ►Epigenetic modulations have been shown to have a role in cancer risk. ►Proanthocyanidins decrease the levels of DNA methylation and histone deacetylation. ►Proanthocyanidins inhibit histone deacetylase activity in skin cancer cells. ►Proanthocyanidins reactivate tumor suppressor genes in skin

Effect of treatment in fractionated schedules with the combination of x-irradiation and six cytotoxic drugs on the RIF-1 tumor and normal mouse skin

International Nuclear Information System (INIS)

Lelieveld, P.; Scoles, M.A.; Brown, J.M.; Phil, D.; Kallman, R.F.

1985-01-01

RIF-1 tumors, implanted syngeneically in the gastrocnemius muscles of the right hind legs of C3H/Km mice, were treated either with X ray alone, drug alone, or drug and X ray combined. The drugs tested were bleomycin, BCNU, cis-diamminedichloro platinum, adriamycin, cyclophosphamide, and actinomycin-D. All drugs were administered either in the maximum tolerated dose or a dose that causes minimal tumor growth delay. Both drugs and X rays were administered either as a single dose or in five daily fractions. In addition to the single modality controls, seven different schedules of combined modalities were tested. Tumors were measured periodically after treatment in order that the day at which each tumor reached 4 times its initial cross-sectional area, i.e., its size at the time of treatment, could be determined. The effect of treatment on tumors was based upon excess growth delay (GD), i.e., T400% (treated)-T400% (untreated control). Treatment effects for the same combined modality schedules were also determined for normal skin, using the early skin reaction as an endpoint. Dose effect factors (DEF) were computed for all combined modality schedules and were based upon calculated radiation dose equivalents. We also calculated supra-additivity ratios, SR/sub I/ and SR/sub II/, therapeutic gain factors and adjusted therapeutic gain factors. The only drugs to produce significant supra-additivity with X rays were cis-Pt and cyclo

Tumor initiating cells in malignant gliomas: biology and implications for therapy.

Science.gov (United States)

Hadjipanayis, Costas G; Van Meir, Erwin G

2009-04-01

A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas.

Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics

International Nuclear Information System (INIS)

Dang, Hien; Ding, Wei; Emerson, Dow; Rountree, C Bart

2011-01-01

Tumor initiating stem-like cells (TISCs) are a subset of neoplastic cells that possess distinct survival mechanisms and self-renewal characteristics crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by TGFβ has been recently linked to the acquisition of TISC characteristics in breast cancer. In HCC, a TISC and EMT phenotype correlates with a worse prognosis. In this work, our aim is to elucidate the underlying mechanism by which cells acquire tumor initiating characteristics after EMT. Gene and protein expression assays and Nanog-promoter luciferase reporter were utilized in epithelial and mesenchymal phenotype liver cancer cell lines. EMT was analyzed with migration/invasion assays. TISC characteristics were analyzed with tumor-sphere self-renewal and chemotherapy resistance assays. In vivo tumor assay was performed to investigate the role of Snail1 in tumor initiation. TGFβ induced EMT in epithelial cells through the up-regulation of Snail1 in Smad-dependent signaling. Mesenchymal liver cancer post-EMT demonstrates TISC characteristics such as tumor-sphere formation but are not resistant to cytotoxic therapy. The inhibition of Snail1 in mesenchymal cells results in decreased Nanog promoter luciferase activity and loss of self-renewal characteristics in vitro. These changes confirm the direct role of Snail1 in some TISC traits. In vivo, the down-regulation of Snail1 reduced tumor growth but was not sufficient to eliminate tumor initiation. In summary, TGFβ induces EMT and TISC characteristics through Snail1 and Nanog up-regulation. In mesenchymal cells post-EMT, Snail1 directly regulates Nanog expression, and loss of Snail1 regulates tumor growth without affecting tumor initiation

Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor

International Nuclear Information System (INIS)

Hwang, Jun-Eul; Yoon, Ju-Young; Bae, Woo-Kyun; Shim, Hyun-Jeong; Cho, Sang-Hee; Chung, Ik-Joo

2010-01-01

Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST. A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities. The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug

The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors.

Science.gov (United States)

Zduniak, Krzysztof; Agrawal, Siddarth; Symonowicz, Krzysztof; Jurczyszyn, Kamil; Ziółkowski, Piotr

2014-03-01

Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a chromosomal protein of unknown function. Its amino acid composition and structure of its DNA binding domain resemble those of high mobility group A (HMGA) proteins which are associated with various malignancies. Since changes in expression of HMGA are considered as a marker of tumor progression, it is possible that similar changes in expression of NUCKS could be a useful tool in diagnosis of malignant skin tumors. To investigate this assumption we used specific antibodies against NUCKS for immunohistochemistry of squamous (SCC) and basal cell carcinoma (BCC) as well as keratoacanthoma (KA). We found high expression of NUCKS in nuclei of SCC and BCC cells which exceeded expression of the well-known proliferation marker Ki67. Expression of NUCKS in benign KA was much below that of malignant tumors. With the present study and based on our previous experience we would like to suggest the NUCKS protein as a novel proliferation marker for immunohistochemical evaluation of formalin-fixed and paraffin-embedded skin tumor specimens. We would like to emphasize that NUCKS abundance in malignant skin tumors is higher than that of the well-known proliferation marker Ki67, thus allowing more precise assessment of tumor proliferation potential.

Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene plus okadaic acid class tumor promoters.

Science.gov (United States)

Fujiki, H; Suganuma, M; Yoshizawa, S; Kanazawa, H; Sugimura, T; Manam, S; Kahn, S M; Jiang, W; Hoshina, S; Weinstein, I B

1989-01-01

Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin-1, and calyculin A, have potent tumor-promoting activity in two-stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and each of these tumor promoters revealed the same mutation at the second nucleotide of codon 61 (CAA----CTA) in the c-Ha-ras gene, determined by the polymerase chain reaction procedure and DNA sequencing. Three potent 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, TPA, teleocidin, and aplysiatoxin, showed the same effects. These results provide strong evidence that this mutation in the c-Ha-ras gene is due to a direct effect of DMBA rather than a selective effect of specific tumor promoters.

Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

Science.gov (United States)

Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

2013-10-01

Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

Maxillary brown tumor as initial presentation of parathyroid adenoma: A case report

Directory of Open Access Journals (Sweden)

Hon-Ke Sia

2012-07-01

Full Text Available Brown tumor is a rare late-stage skeletal change caused by long-term stimulation of excess parathyroid hormone. It is not neoplastic, but a reparative cellular process. Common sites of brown tumor are the ribs, clavicle, long bones and pelvic girdle. Solitary maxillary brown tumor as initial presentation of primary hyperparathyroidism is rare; it is often accompanied by brown tumors of the other facial bones. Here, we present the first case of solitary maxillary brown tumor in a 29-year-old ethnic Chinese woman with initial presentation of a large tumor filling the left maxillary sinus. Underlying long-standing primary hyperparathyroidism caused by a large parathyroid adenoma was finally diagnosed. Brown tumor tends to be misdiagnosed as malignancy, and delayed diagnosis of the underlying hyperparathyroidism is common. Our case validates the suggestion that young women have a higher probability of brown tumor. Biopsy of the suspicious bone tumor and blood tests for calcium and parathyroid hormone level are crucial and essential to reach the correct diagnosis. Most brown tumors show spontaneous regression after parathyroidectomy. However, direct excision of the brown tumor may be indicated to avoid the risk of facial deformity and orbital compression at a special anatomical site, as in our case.

Late health effects of childhood nasopharyngeal radium irradiation: nonmelanoma skin cancers, benign tumors, and hormonal disorders

NARCIS (Netherlands)

Ronckers, Cécile M.; Land, Charles E.; Hayes, Richard B.; Verduijn, Pieter G.; Stovall, Marilyn; van Leeuwen, Flora E.

2002-01-01

Nasopharyngeal radium irradiation (NRI) was widely used from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for benign tumors, nonmelanoma skin cancer, thyroid disorders, and conditions

A case of radiation-induced skin ulcer, cerebral meningioma and skin cancer

International Nuclear Information System (INIS)

Matsuo, Yuki; Yano, Kenji

2000-01-01

We report a case of radiation-induced skin ulcer, cerebral meningioma, and skin cancer in a 69-year-old woman who had undergone local irradiation and application of radium directly to the skin for actinomycosis of the face at the age of twenty. Some forty to fifty years later, a skin ulcer in the preauricular area in the center of the radiodermatitis, cerebral meningioma in the right sphenoid ridge, and a keratotic skin tumor in the right auricle all developed within the previously irradiated region. The cerebral meningioma was extirpated. The skin ulcer was excised and covered with a forearm flap. After the skin tumor was excised and the subcutaneous tumor in the postauricular area was excised, the postoperative histopathological diagnosis was squamous cell carcinoma with lymph node metastasis. It was considered that the squamous cell carcinoma was derived from irradiated keratosis. Four months later, right neck lymph node dissection was performed. Both the meningioma and squamous cell carcinoma satisfied Cahan's criteria for radiation-induced tumors. So we diagnosed these as radiation-induced cerebral meningioma and squamous cell carcinoma. We haven't detected any recurrence of the squamous cell carcinoma for two years. We learned from this case that chronic radiation disturbances cause an irreversible reaction and various radiolesions, including malignancies, can occur after a long period of latency. It is important to never underestimate a small lesion in the irradiated area, to plan early preventive surgical treatment to remove skin that may have been over-subjected to irradiation, and to continue long-term follow-up for patients with chronic radiodermatitis. (author)

Experimental skin carcinoma by UVB application

Directory of Open Access Journals (Sweden)

Andrada Iftode

2016-12-01

Full Text Available OBJECTIVES AND BACKGROUND The aim of this research study was to evaluate the harmful effects at skin level induced by concomitant and repeated exposure to three toxic agents: UVB radiation, DMBA and TPA. MATERIALS AND METHODS Experimental mice were divided in thw following groups (n=5 mice/group: group 1 – healthy mice, group 2 – mice exposed to UVB – radiation and topical administration of acetone and group 3 – mice exposed to UVB – radiation and topical application of DMBA and TPA solutions (phase I - double tumor initiation and phase II - tumor promotion. RESULTS Application of these compounds led to the development of skin papilloma and to significant changes in skin parameters. CONCLUSIONS The barrier function of the skin was degraded in UVB exposed mice. DMBA and TPA depended on carcinogens schedule and corelated with skin carcinoma. Graphical abstract: Schematic protocol of experimental skin carcinoma REFERENCES 1. Lee Ja, Ko Jh, Jung Bg, Kim Th, Hong Ji, Park Ys, Lee Bj. Fermented Prunus mume with Probiotics Inhibits 7,12- Dimethylbenz[a]anthracene and 12-OTetradecanoyl phorbol-13-acetate Induced Skin Carcinogenesis through Alleviation of Oxidative Stress. Asian Pac J Cancer Prev. 2013;14:2973-2978. 2. Firooz A, Sadr B, Babakoohi S, Sarraf-Yazdy M, Fanian F, Kazerouni-Timsar A, NassiriKashani M, Naghizadeh MM, Dowlati Y. Variation of Biophysical Parameters of the Skin with Age, Gender, and Body Region. Scientific World Journal. 2012; doi.org/10.1100/2012/386936 3. Gheorgheosu (Coricovac D, Borcan F, Balasz NI, Soica C, Simu G, Kemeny L, Dehelean CA. Evaluation of skin parameters in C57BL/6J mice exposed to chemical and environmental factors using non-invasive methods. J Agroalim Proc Technol. 2014;20:14-20.

Strain differences in mouse skin carcinogenesis experiments using ionizing radiation and the tumor promoter TPA

International Nuclear Information System (INIS)

Jaffe, D.R.; Bowden, G.T.

1985-01-01

Ionizing radiation has been shown to be a complete carcinogen in rodent skin when administered repeatedly. The initiating potential of ionizing radiation in mouse skin was tested in a classical two-stage protocol in both CD-1 and Sencar mice. Beta radiation (0.5, 1.5, 3.0 and 5.0 Gy) was administered by a strontium 90 applicator followed two weeks later by twice weekly application of 5 μg TPA. A statistical difference in the papilloma incidence between radiation initiated, TPA promoted versus non-initiated TPA promoted groups was not found (25-35% animals with papillomas and 0.35-0.45 papillomas per mouse at 65 weeks of promotion for both initiated and non-initiated mice). There appeared to be no strain differences between the CD-1 and Sencar in response to the initiating effects if ionizing radiation. This is in direct contrast to the studies showing Sencar mice to be much more sensitive than CD-1 to the initiating effects of chemical carcinogens

Tumors of the skin and soft tissues

Energy Technology Data Exchange (ETDEWEB)

Weller, R.E.

1991-10-01

The majority of the body surface is covered by the skin. Many internal disorders are reflected in the condition of the skin. One of the major functions of the skin is protection of the other organ systems from a variety of environmental insults. In this role, the skin itself is exposed to factors that can ultimately cause chronic diseases and cancer. Since it is relatively easy to recognize skin abnormalities, most skin cancers are brought to professional attention sooner than other types of cancer. However, due to the close resemblance between many skin neoplasms and noncancerous dermatologic disorders, these neoplasms may be mistreated for months or even years. In veterinary oncology, as in human medicine, most cancers can be effectively treated or cured following an accurate diagnosis. Once diagnosed, skin neoplasms should be aggressively treated. If causal factors are known, exposure to these factors should be limited through removal of the agent (for chemical carcinogens) or limiting exposure to the agent (for other carcinogens such as sunlight). 10 tabs. (MHB)

Studies of skin cancer and thyroid tumors after irradiation of the head and neck

International Nuclear Information System (INIS)

Shore, R.E.; Moseson, M.; Hildreth, N.

1992-01-01

Two longitudinal studies of children given medical X-irradiation to the head and neck are described, one of 2,650 infants who received x-ray treatment for enlarged thymus glands and the other of 2,200 children who received x-ray treatment for tinea capitis (ringworm of the scalp). The thymus study showed a dose-related excess of thyroid cancer and a long period of excess risk. The tinea study also showed an excess of thyroid tumors even though the thyroid dose was only about 0.06 Gy. An excess of non-melanotic skin cancers has also occurred in the tinea study, but no evidence for excess malignant melanomas. The skin cancer excess is not evident among blacks in the study, and, among Caucasians, it is more prominent among those with a light complexion. This suggests that host-susceptibility to ultraviolet effects is an important modifier of skin cancer risk from ionizing irradiation. (author)

An inhibitor of K+ channels modulates human endometrial tumor-initiating cells

Directory of Open Access Journals (Sweden)

Leslie Kimberly K

2011-08-01

Full Text Available Abstract Background Many potassium ion (K+ channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC, are critical to cancer progression. Results A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA, was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.

The spectrum of skin biopsies and excisions in a pediatric skin center.

Science.gov (United States)

Theiler, Martin; Neuhaus, Kathrin; Kerl, Katrin; Weibel, Lisa

2017-12-01

Little is known about the spectrum of pediatric skin disorders requiring biopsy/excision, their indication, impact on further management, and the accuracy of clinical diagnosis. We aimed to address these questions in the patient population seen at our Swiss University referral center for Pediatric Dermatology and Plastic Surgery. All skin biopsies/excisions performed in patients aged ≤ 16 years over a period of 2 years were retrospectively analyzed. A total of 506 samples were included. The majority of biopsies/excisions (n = 413, 82%) was performed for tumors, cysts, and hamartomas and 18% for other skin conditions. Malignant tumors were found in 12 samples (2%) from four patients. In 121 (24%) patients, the histopathology had an important impact on patient management. In 80 (16%) cases, the pathology did not match with the clinical diagnosis. In 382 (75%) cases, excision was the treatment of choice. Of these, the indication for surgery was based on patient's request in 181 (47%) cases. Surgical interventions for pediatric skin disorders are performed for diagnostic and therapeutic reasons. In this cohort, histopathology was essential for treatment in one quarter of cases. Skin tumors, cysts, and hamartomas often require excision during childhood, with families' request and esthetic considerations playing an important role. What is Known: • The spectrum of pediatric skin conditions has been studied in outpatient, inpatient, and emergency settings. • In contrast, no data exist on the spectrum of pediatric skin disorders undergoing biopsy/excision specifically. What is New: • We analyze biopsies/excisions in children, focusing on diagnosis, indication, and impact on patient management. • Surgical interventions for skin disorders in children are often performed for tumors and hamartomas with esthetic considerations playing a relevant role. If used for diagnostic purposes, they are often performed to confirm or rule out severe skin disease.

A case of radiation-induced skin ulcer, cerebral meningioma and skin cancer

Energy Technology Data Exchange (ETDEWEB)

Matsuo, Yuki; Yano, Kenji [Kure National Hospital, Hiroshima (Japan)

2000-10-01

We report a case of radiation-induced skin ulcer, cerebral meningioma, and skin cancer in a 69-year-old woman who had undergone local irradiation and application of radium directly to the skin for actinomycosis of the face at the age of twenty. Some forty to fifty years later, a skin ulcer in the preauricular area in the center of the radiodermatitis, cerebral meningioma in the right sphenoid ridge, and a keratotic skin tumor in the right auricle all developed within the previously irradiated region. The cerebral meningioma was extirpated. The skin ulcer was excised and covered with a forearm flap. After the skin tumor was excised and the subcutaneous tumor in the postauricular area was excised, the postoperative histopathological diagnosis was squamous cell carcinoma with lymph node metastasis. It was considered that the squamous cell carcinoma was derived from irradiated keratosis. Four months later, right neck lymph node dissection was performed. Both the meningioma and squamous cell carcinoma satisfied Cahan's criteria for radiation-induced tumors. So we diagnosed these as radiation-induced cerebral meningioma and squamous cell carcinoma. We haven't detected any recurrence of the squamous cell carcinoma for two years. We learned from this case that chronic radiation disturbances cause an irreversible reaction and various radiolesions, including malignancies, can occur after a long period of latency. It is important to never underestimate a small lesion in the irradiated area, to plan early preventive surgical treatment to remove skin that may have been over-subjected to irradiation, and to continue long-term follow-up for patients with chronic radiodermatitis. (author)

Vascular thermal adaptation in tumors and normal tissue in rats

International Nuclear Information System (INIS)

Nah, Byung Sik; Choi, Ihl-Bohng; Oh, Won Young; Osborn, James L.; Song, Chang W.

1996-01-01

Purpose: The vascular thermal adaptation in the R3230 adenocarcinoma, skin and muscle in the legs of Fischer rats was studied. Methods and Materials: The legs of Fischer rats bearing the R3230 AC adenocarcinoma (subcutaneously) were heated once or twice with a water bath, and the blood flow in the tumor, skin and muscle of the legs was measured with the radioactive microsphere method. Results: The blood flow in control R3230 AC tumors was 23.9 ml/100 g/min. The tumor blood flow increased about 1.5 times in 30 min and then markedly decreased upon heating at 44.5 deg. C for 90 min. In the tumors preheated 16 h earlier at 42.5 deg. C for 60 min, reheating at 44.5 deg. C increased the tumor blood flow by 2.5-fold in 30 min. Contrary to the decline in blood flow following an initial increase during the 44.5 deg. C heating without preheating, the tumor blood flow remained elevated throughout the 90 min reheating at 44.5 deg. C. These results indicated that thermal adaptation or thermotolerance developed in the tumor vasculatures after the preheating at 42.5 deg. C for 60 min. The magnitude of vascular thermal adaptation in the tumors 24 h and 48 h after the preheating, as judged from the changes in blood flow, were smaller than that 16 h after the preheating. Heating at 42.5 deg. C for 60 min induced vascular thermal adaptation also in the skin and muscle, which peaked in 48 h and 24 h, respectively, after the heating. Conclusion: Heating at 42.5 deg. C for 1 h induced vascular thermal adaptation in the R3230 AC tumor, skin, and muscle of rats that peaked 16-48 h after the heating. When the tumor blood vessels were thermally adapted, the tumor blood flow increased upon heating at temperatures that would otherwise reduce the tumor blood flow. Such an increase in tumor blood flow may hinder raising the tumor temperature while it may increase tumor oxygenation.

Tumor attributes predicting cutaneous metastatic destiny: a report of two interesting cases.

Science.gov (United States)

Gurumurthi, Ravichandran; Thirumalai, Raja; Easow, Jose M; Mohan, Subhashini

2014-07-01

Cutaneous metastases are the result of complex interaction between the tumor cells ("seed") and the host environment ("soil"). Metastases to the skin can be an early sign of internal malignancy or represent recurrence of the primary tumor and portends a poorer prognosis. Invasion and metastasis are the hallmarks of on cogenesis. Skin is the largest organ in the body, but the incidence of metastases is low. With advances in molecular biology, factors responsible for the initiation and perpetuation of metastatic tumor cells at distant sites are being elucidated. The concept of "pre-metastatic niche" and interaction between various chemokines has given a new outlook in understanding the organ specificity of metastatic tumor cells. We present two cases of cutaneous metastases with interesting clinical findings correlating with its biologic subtypes.

Extraoral tumor-like granuloma as a symptom of dental infection

DEFF Research Database (Denmark)

Werner Madsen, Sanne; Søgaard, Sara Taylor; Schmidt, Grethe

2016-01-01

A 26-year old woman with a cutaneous granuloma and fistula caused by a dental infection was initially mistaken for a tumor. She was under diagnostic examinations at several health care providers for 1.5 years before a final diagnosis and treatment was reached. The fistula originated from a periap...... always be suspected. Relevant imaging of the teeth and jaws will usually reveal the cause. The medical history, the oral and skin findings, biopsy, imaging results and treatment are presented in this article.......A 26-year old woman with a cutaneous granuloma and fistula caused by a dental infection was initially mistaken for a tumor. She was under diagnostic examinations at several health care providers for 1.5 years before a final diagnosis and treatment was reached. The fistula originated from...... a periapical lesion and extended to the facial skin. Differential diagnoses include malignant tumor, bacterial infection, furuncle and a granulomatous-like lesion. When a patient is presented with a fistula or granuloma-like lesion on the cheek, chin or the submandibular region, a dental infection should...

A novel mechanism of skin tumor promotion involving interferon-gamma (IFNγ)/signal transducer and activator of transcription-1 (Stat1) signaling.

Science.gov (United States)

Bozeman, Ronald; Abel, Erika L; Macias, Everardo; Cheng, Tianyi; Beltran, Linda; DiGiovanni, John

2015-08-01

The current study was designed to explore the role of signal transducer and activator of transcription 1 (Stat1) during tumor promotion using the mouse skin multistage carcinogenesis model. Topical treatment with both 12-O-tetradecanoylphorbol-13-acetate (TPA) and 3-methyl-1,8-dihydroxy-9-anthrone (chrysarobin or CHRY) led to rapid phosphorylation of Stat1 on both tyrosine (Y701) and serine (S727) residues in epidermis. CHRY treatment also led to upregulation of unphosphorylated Stat1 (uStat1) at later time points. CHRY treatment also led to upregulation of interferon regulatory factor 1 (IRF-1) mRNA and protein, which was dependent on Stat1. Further analyses demonstrated that topical treatment with CHRY but not TPA upregulated interferon-gamma (IFNγ) mRNA in the epidermis and that the induction of both IRF-1 and uStat1 was dependent on IFNγ signaling. Stat1 deficient (Stat1(-/-) ) mice were highly resistant to skin tumor promotion by CHRY. In contrast, the tumor response (in terms of both papillomas and squamous cell carcinomas) was similar in Stat1(-/-) mice and wild-type littermates with TPA as the promoter. Maximal induction of both cyclooxygenase-2 and inducible nitric oxide synthase in epidermis following treatment with CHRY was also dependent on the presence of functional Stat1. These studies define a novel mechanism associated with skin tumor promotion by the anthrone class of tumor promoters involving upregulation of IFNγ signaling in the epidermis and downstream signaling through activated (phosphorylated) Stat1, IRF-1 and uStat1. © 2014 Wiley Periodicals, Inc.

A Targetable EGFR-Dependent Tumor-Initiating Program in Breast Cancer

Directory of Open Access Journals (Sweden)

Paul Savage

2017-10-01

Full Text Available Summary: Therapies targeting epidermal growth factor receptor (EGFR have variable and unpredictable responses in breast cancer. Screening triple-negative breast cancer (TNBC patient-derived xenografts (PDXs, we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing of 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated EGFR expression was significantly enriched in a mesenchymal/stem-like cellular cluster. Sorted EGFRhi subpopulations exhibited enhanced stem-like features, including ALDH activity, sphere-forming efficiency, and tumorigenic and metastatic potential. EGFRhi cells gave rise to EGFRhi and EGFRlo cells in primary and metastatic tumors, demonstrating an EGFR-dependent expansion and hierarchical state transition. Similar tumorigenic EGFRhi subpopulations were identified in independent PDXs, where heterogeneous EGFR expression correlated with gefitinib sensitivity. This provides new understanding for an EGFR-dependent hierarchy in TNBC and for patient stratification for therapeutic intervention. : Savage et al. demonstrate that sensitivity to EGFR inhibitor, gefitinib, in triple-negative breast cancer is paradoxically associated with EGFR heterogeneity. Using single-cell RNA sequencing in conjunction with functional assays, they identify TNBC tumors in which EGFR expression identifies cells with tumor-initiating capacity whose proliferative expansion is sensitive to EGFR inhibition. Keywords: breast cancer, tumor heterogeneity, patient-derived xenograft, single-cell RNA sequencing, EGFR inhibition, therapeutic response, tumor-initiating cell, cell hierarchy, BRCA1 mutation

Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

Science.gov (United States)

Iwase, Y; Takemura, Y; Ju-ichi, M; Ito, C; Furukawa, H; Kawaii, S; Yano, M; Mou, X Y; Takayasu, J; Tokuda, H; Nishino, H

2000-06-01

To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

The importance of skin-to-skin contact for early initiation of breastfeeding in Nigeria and Bangladesh.

Science.gov (United States)

Singh, Kavita; Khan, Shane M; Carvajal-Aguirre, Liliana; Brodish, Paul; Amouzou, Agbessi; Moran, Allisyn

2017-12-01

Skin-to-skin contact (SSC) between mother and newborn offers numerous protective effects, however it is an intervention that has been under-utilized. Our objectives are to understand which newborns in Bangladesh and Nigeria receive SSC and whether SSC is associated with the early initiation of breastfeeding. Demographic and Health Survey (DHS) data were used to study the characteristics of newborns receiving SSC for non-facility births in Nigeria (DHS 2013) and for both facility and non-facility births in Bangladesh (DHS 2014). Multivariable logistic regression was used to study the association between SSC and early initiation of breastfeeding after controlling for key socio-demographic, maternal and newborn-related factors. Only 10% of newborns in Nigeria and 26% of newborns in Bangladesh received SSC. In the regression models, SSC was significantly associated with the early initiation of breastfeeding in both countries (OR = 1.42, 95% CI 1.15-1.76 for Nigeria; OR = 1.27, 95% CI 1.04-1.55, for Bangladesh). Findings from the regression analysis for Bangladesh revealed that newborns born by Cesarean section had a 67% lower odds of early initiation of breastfeeding than those born by normal delivery (OR = 0.33, 95% CI 0.26-0.43). Also in Bangladesh newborns born in a health facility had a 30% lower odds of early initiation of breastfeeding than those born in non-facility environments (OR = 0.70, 95% CI 0.53-0.92). Early initiation of breastfeeding was significantly associated with parity, urban residence and wealth in Nigeria. Geographic area was significant in the regression analyses for both Bangladesh and Nigeria. Coverage of SSC is very low in the two countries, despite its benefits for newborns without complications. SSC has the potential to save newborn lives. There is a need to prioritize training of health providers on the implementation of essential newborn care including SSC. Community engagement is also needed to ensure that all women and

Advances in the in Vivo Raman Spectroscopy of Malignant Skin Tumors Using Portable Instrumentation

Directory of Open Access Journals (Sweden)

Nikolaos Kourkoumelis

2015-06-01

Full Text Available Raman spectroscopy has emerged as a promising tool for real-time clinical diagnosis of malignant skin tumors offering a number of potential advantages: it is non-intrusive, it requires no sample preparation, and it features high chemical specificity with minimal water interference. However, in vivo tissue evaluation and accurate histopathological classification remain a challenging task for the successful transition from laboratory prototypes to clinical devices. In the literature, there are numerous reports on the applications of Raman spectroscopy to biomedical research and cancer diagnostics. Nevertheless, cases where real-time, portable instrumentations have been employed for the in vivo evaluation of skin lesions are scarce, despite their advantages in use as medical devices in the clinical setting. This paper reviews the advances in real-time Raman spectroscopy for the in vivo characterization of common skin lesions. The translational momentum of Raman spectroscopy towards the clinical practice is revealed by (i assembling the technical specifications of portable systems and (ii analyzing the spectral characteristics of in vivo measurements.

Pyrrolizidine Alkaloids: Metabolic Activation Pathways Leading to Liver Tumor Initiation.

Science.gov (United States)

Fu, Peter P

2017-01-17

Pyrrolizidine alkaloids (PAs) and PA N-oxides are a class of phytochemical carcinogens contained in over 6000 plant species spread around the world. It has been estimated that approximately half of the 660 PAs and PA N-oxides that have been characterized are cytotoxic, genotoxic, and tumorigenic. It was recently determined that a genotoxic mechanism of liver tumor initiation mediated by PA-derived DNA adducts is a common metabolic activation pathway of a number of PAs. We proposed this set of PA-derived DNA adducts could be a common biological biomarker of PA exposure and a potential biomarker of PA-induced liver tumor formation. We have also found that several reactive secondary pyrrolic metabolites can dissociate and interconvert to other secondary pyrrolic metabolites, resulting in the formation of the same exogenous DNA adducts. This present perspective reports the current progress on these new findings and proposes future research needed for obtaining a greater understanding of the role of this activation pathway and validating the use of this set of PA-derived DNA adducts as a biological biomarker of PA-induced liver tumor initiation.

Sunlight suppressing rejection of 280- to 320-nm UV-radiation-induced skin tumors in mice

International Nuclear Information System (INIS)

Morison, W.L.; Kelley, S.P.

1985-01-01

Repeated exposure of female C3H/HeNCR- mice to sunlight prevented the normal immunologic rejection of a UV-induced tumor. This systemic immunologic alteration was transferred to syngeneic lethally X-irradiated animals with lymphoid cells from mice exposed to sunlight. The lymphoid cells also were able to suppress the capacity of lymphoid cells from normal animals to reject a UV-induced tumor. The 295- to 320-nm wave band appeared to be responsible for this immunosuppressive effect of sunlight because suppression was prevented by filtration of the radiation through Mylar and by application of a sunscreen containing para-aminobenzoic acid. These observations may have importance in understanding the pathogenesis of sunlight-induced skin cancer in humans

Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha.

Science.gov (United States)

Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

2016-09-01

Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. The purpose of this study was to evaluate skin barrier function during chronic liver injury. Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.

CD200-expressing human basal cell carcinoma cells initiate tumor growth.

Science.gov (United States)

Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

2013-01-22

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

Elaboration of an algorithm for preserving a projective skin flap above the tumor when planning subcutaneous mastectomy from an aesthetically acceptable area in patients with breast nodule cancer

Directory of Open Access Journals (Sweden)

A. R. Khamitov

2016-01-01

Full Text Available Indications for the conservation of the skin flap over the tumor for potential offset of the operational access in aesthetically acceptable zone in patients with primary nodular breast cancer are discussed in the article. The survey results of 203 patients (T1–2N0–3M0 are analyzed. The study revealed that the risk factors affecting the skin flap involvement are the presence of the skin flattening as well as topographic and anatomical characteristics: tumor < 3 cm, located at a depth of < 0.46 ± 0.2 cm, tumor ≥ 3 cm located at a depth of < 1.66 cm. Based on the data the algorithm for immediate breast reconstruction from aesthetically acceptable zone for surgical oncologist is compiled.

Quantification of tumour initiating effect of jute batching oil and its distillates over mouse skin.

Science.gov (United States)

Agarwal, R; Kumar, S; Shukla, Y; Antony, M; Mehrotra, N K

1985-09-30

In order to identify the tumour initiating constituent(s) of a mineral oil, jute batching oil (JBO), used in the processing of jute fibres, it was fractionally distilled in various boiling range fractions. The latter were then subjected to in vivo assessment of their aryl hydrocarbon hydroxylase (AHH) inducing potential in mouse epidermis. Fractions with almost similar AHH inducing potential were regrouped and studied for their tumour initiating potential over mouse skin following two-stage initiation-promotion protocol and using 12-O-tetradecanoyl phorbol-13-acetate (TPA) as tumour promoter. It was noticed that: (1) JBO as initiator, provoked local development of benign skin tumours over mouse back; (2) fractions of JBO boiling below 335 degrees C and above 399 degrees C accounted for most of the tumour initiating potential of the oil; (3) the histological features of the tumours (i.e. benign papillomas and keratoacanthomas) initiated by these fractions were similar to those developed after being initiated with unfractionated or reconstituted JBO; (4) removal of these fractions from JBO may be attempted which could decontaminate the batch oil from most of its tumorigenic components and make it safer for industrial use.

Tumor necrosis factor-α-accelerated degradation of type I collagen in human skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo

DEFF Research Database (Denmark)

Ågren, Magnus S; Schnabel, Reinhild; Christensen, Lise H

2015-01-01

Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10ng/ml) in the a......Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10ng...... tissue-derived collagenolytic activity with TNF-α exposure was blocked by neutralizing MMP-1 monoclonal antibody and was not due to down-regulation of tissue inhibitor of metalloproteinase-1. TNF-α increased production (pendogenous MMP-1...

Three-Dimensional In Vitro Skin and Skin Cancer Models Based on Human Fibroblast-Derived Matrix.

Science.gov (United States)

Berning, Manuel; Prätzel-Wunder, Silke; Bickenbach, Jackie R; Boukamp, Petra

2015-09-01

Three-dimensional in vitro skin and skin cancer models help to dissect epidermal-dermal and tumor-stroma interactions. In the model presented here, normal human dermal fibroblasts isolated from adult skin self-assembled into dermal equivalents with their specific fibroblast-derived matrix (fdmDE) over 4 weeks. The fdmDE represented a complex human extracellular matrix that was stabilized by its own heterogeneous collagen fiber meshwork, largely resembling a human dermal in vivo architecture. Complemented with normal human epidermal keratinocytes, the skin equivalent (fdmSE) thereof favored the establishment of a well-stratified and differentiated epidermis and importantly allowed epidermal regeneration in vitro for at least 24 weeks. Moreover, the fdmDE could be used to study the features of cutaneous skin cancer. Complementing fdmDE with HaCaT cells in different stages of malignancy or tumor-derived cutaneous squamous cell carcinoma cell lines, the resulting skin cancer equivalents (fdmSCEs) recapitulated the respective degree of tumorigenicity. In addition, the fdmSCE invasion phenotypes correlated with their individual degree of tissue organization, disturbance in basement membrane organization, and presence of matrix metalloproteinases. Together, fdmDE-based models are well suited for long-term regeneration of normal human epidermis and, as they recapitulate tumor-specific growth, differentiation, and invasion profiles of cutaneous skin cancer cells, also provide an excellent human in vitro skin cancer model.

Therapeutic potential of the anti-diabetic agent metformin in targeting the skin cancer stem cell diaspora.

Science.gov (United States)

Reddi, Anand; Powers, Matthew A; Dellavalle, Robert P

2014-05-01

Type II diabetes is associated with increased prevalence of cancer including both melanoma and squamous cell carcinoma (SCC) of the skin. Emerging evidence from epidemiological studies suggest that diabetic patients on metformin have a lower risk of cancer incidence and mortality in a broad range of neoplasms. In both melanoma and SCC, populations of cancer stem cells (CSC) contribute to tumor initiation and metastasis. We propose that metformin constitutes a new class of targeted therapy that acts on the skin CSC diaspora. We posit that metformin selectively and simultaneously targets CSCs of the primary tumor as well as in metastatic niches thereby disrupting the dynamic dispersal of circulating CSCs between the primary tumor and metastatic site. This hypothesis suggests a new concept in dermato-oncology that treatment of type II diabetes and prevention of skin cancer are two sides of the same coin. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In Vivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors

Directory of Open Access Journals (Sweden)

Nabendu Pore

2015-06-01

Full Text Available Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up-regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX, monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model.

SOCS3 inhibits the pathological effects of IL-22 in non-melanoma skin tumor-derived keratinocytes.

Science.gov (United States)

Madonna, Stefania; Scarponi, Claudia; Morelli, Martina; Sestito, Rosanna; Scognamiglio, Pasqualina Liana; Marasco, Daniela; Albanesi, Cristina

2017-04-11

Basal cell carcinomas (BCC) and squamous-cell carcinomas (SCC) are common malignancies in humans, caused by neoplastic transformation of keratinocytes of the basal or suprabasal layers of epidermis, respectively. Tumor-infiltrating lymphocytes (TILs) are frequently found in BCC and SCC, and functionally promote epithelial carcinogenesis. TILs secreting IL-22, in particular, participate to BCC and SCC growth by inducing keratinocyte proliferation and migration, as well as the expression of inflammatory, anti-apoptotic and pro-angiogenic genes.In this study, we identified SOCS3 as a valid candidate to be manipulated for suppressing tumorigenic functions in BCC and SCC. We found that SOCS3 and SOCS1 expression was reduced in vivo, in tumor lesions of BCC and SCC, as compared to other skin inflammatory conditions such as psoriasis, despite the high number of IL-22-secreting TILs. Moreover, IL-22 was not able to induce in vitro the transcriptional expression of SOCS3 in BCC-or SCC-derived keratinocytes, contrarily to healthy cells. Aimed at rescuing SOCS3 activity in these tumor contexts, a SOCS3-derived peptide, named KIR-ESS, was synthesized, and its ability in suppressing IL-22-induced responses was evaluated in healthy and transformed keratinocytes. We found that KIR-ESS peptide efficiently suppressed the IL-22 molecular signaling in keratinocytes, by acting on STAT3 and Erk1/2 cascade, as well as on the expression of STAT3-dependent downstream genes. Interestingly, after treatment with peptide, both healthy and transformed keratinocytes could no longer aberrantly proliferate and migrate in response to IL-22. Finally, treatment of athymic nude mice bearing SCC xenografts with KIR-ESS peptide concomitantly reduced tumor growth and activated STAT3 levels. As a whole, these data provides the rationale for the use in BCC and SCC skin tumors of SOCS3 mimetics, being able to inhibit the deleterious effects of IL-22 in these contexts.

Morphological changes in skin tumors caused by pulsed laser irradiation

Energy Technology Data Exchange (ETDEWEB)

Moskalik, K G; Lipova, V A; Neyshtadt, E L

1979-01-01

Morphological changes induced by treating melanomas, basaloma and flatcell skin cancers with a pulsed neodymium laser at 1060 nm, pulse length 1 msec and energy 250 to 500 J/cm/sup 2/, were studied using impressions and scrapings from the affected area. Nuclear pyknosis, nuclear and cellular elongation, vacuolization, frequent complete loss of cytoplasm, particulaly in the zone of direct irradiation, and loss of cellular structure were seen. These dystrophic changes increased with closeness to the zone of direct irradiation, culminating in necrosis. Formed and decomposed blood elements and melanin accumulated in the intracellular spaces, due to disruption of capillaries and small arteries and veins. Fewer and more aggregated melanoblasts were found after melanoma irradiation. Nuclear chromatin fusion, cytoplasmic changes and altered cell shape were observed. Basaloma cells were clustered and elongated after irradiation, with many fibrous structures and loss of cellular elements. Cytoplasmic vacuolization and lysis, bare nuclei, karyolysis, karyorrhexis and karyopyknosis were seen in corneous flat-cell cancer. In the few cases in which malignant cells were found under the scab from the first treatment the procedure was repeated. The morphological changes induced by pulsed laser irradiation are very similar to electrocoagulation necrosis, but are more localized. The ability of low and middle energy lasers to induce thrombosis and coagulation in vascular walls reduced the probability of hematogenic tumor cell dissemination. Cytological examination is highly effective in determining the degree of radical skin cancer healing due to laser treatment. 12 references, 2 figures.

CENP-R acts bilaterally as a tumor suppressor and as an oncogene in the two-stage skin carcinogenesis model.

Science.gov (United States)

Okumura, Kazuhiro; Kagawa, Naoko; Saito, Megumi; Yoshizawa, Yasuhiro; Munakata, Haruka; Isogai, Eriko; Fukagawa, Tatsuo; Wakabayashi, Yuichi

2017-11-01

CENP-R is a component of the CENP-O complex, including CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP-R-deficient chicken DT40 cells are viable and show a very minor effect on mitosis. To investigate the functional roles of CENP-R in vivo, we generated CENP-R-deficient mice (Cenp-r -/- ). Mice heterozygous or homozygous for Cenp-r null mutation are viable and healthy, with no apparent defect in growth and morphology, indicating Cenp-r is not essential for normal development. Accordingly, to investigate the role of the Cenp-r gene in skin carcinogenesis, we subjected Cenp-r -/- mice to the 7,12-dimethylbenz(a)anthracene (DMBA)/TPA chemical carcinogenesis protocol and monitored tumor development. As a result, Cenp-r -/- mice initially developed significantly more papillomas than control wild-type mice. However, papillomas in Cenp-r -/- mice showed a decrease of proliferative cells and an increase of apoptotic cells. As a result, they did not grow bigger and some papillomas showed substantial regression. Furthermore, papillomas in Cenp-r -/- mice showed lower frequency of malignant conversion to squamous cell carcinomas. These results indicate Cenp-r functions bilaterally in cancer development: during early developmental stages, Cenp-r functions as a tumor suppressor, but during the expansion and progression of papillomas it functions as a tumor-promoting factor. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Epidermal changes following application of 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate to human skin transplanted to nude mice studied with histological species markers

International Nuclear Information System (INIS)

Graem, N.

1986-01-01

Effects of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) and of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on epidermis of human fetal and adult skin were studied in the nude mouse/human skin model. Human skin grafts on NC nude mice were exposed to two topical applications of 1 mg of DMBA in 50 microliter of acetone with an interval of 3 days and/or to applications of 10 micrograms of TPA in 50 microliter of acetone twice weekly. In some animals, it was attempted to augment the susceptibility of the grafts to the tumor-initiating effect of DMBA by pretreatment with TPA or ultraviolet light. The mice were sacrificed 8-32 wk after the initial treatment. Tumors did not appear in the central portions of any of the grafts, but epidermal tumors were seen at the graft border in 34.9% of the DMBA-treated animals. To identify human epidermis on the grafts and to determine the species origin of the induced tumors, two independently working histological marker methods were applied. (a) The first is detection of a human Blood Group B-like antigen present in mouse epidermis and in chemically induced murine epidermal tumors. This antigen cannot be demonstrated in human epidermis and in epidermal tumors of human patients. (b) The second is histological staining with the DNA-specific fluorochrome, bisbenzimide, displaying a characteristic pattern of 5-10 intranuclear fluorescent bodies in murine nonneoplastic epidermal cells and in murine epidermal tumor cells. Such a pattern is not seen in human epidermis and in epidermal tumors of human patients. The studies showed that TPA treatment resulted in epidermal hyperplasia in both the human epidermis and the adjacent mouse epidermis and that the induced tumors were derived from murine tissue

Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

Directory of Open Access Journals (Sweden)

Yonatan Y Mahller

Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

Radiolabeled F(ab')2-cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models.

Science.gov (United States)

Bellaye, P-S; Moreau, M; Raguin, O; Oudot, A; Bernhard, C; Vrigneaud, J-M; Dumont, L; Vandroux, D; Denat, F; Cochet, A; Brunotte, F; Collin, B

2018-05-17

This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111 In and 177 Lu, respectively. We designed F(ab') 2 -fragments of cetuximab radiolabeled with 111 In and 177 Lu. 111 In-F(ab') 2 -cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111 In-F(ab') 2 -cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177 Lu-F(ab') 2 -cetuximab was evaluated in SWISS nude mice bearing A431 tumors. Radiolabeling procedure did not change F(ab') 2 -cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111 In-DOTAGA-F(ab') 2 -cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab') 2 -cetuximab. SPECT imaging of 111 In-DOTAGA-F(ab') 2 -cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, 177 Lu-DOTAGA-F(ab') 2 -cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses. 111 In-DOTAGA-F(ab') 2 -cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. 177 Lu-DOTAGA-F(ab') 2 -cetuximab is an interesting theranostic tool allowing therapy and imaging.

Studies on the production and utilization of radioisotopes - Treatment of= skin cancer with Ho-166 skin patch in an animal model

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Rok [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Lee, Jong Doo [Yonsei University, Seoul (Korea, Republic of)

1995-07-01

Skin cancers were developed in 8 ICR mice and 2 hairless mice by topical application of chemical compound (TDA and NPO) for 35 wks. Specially designed= Ho-166 skin patches were applied over the skin cancer for 1-2 hrs to deliver 8000 rads to the tumors. Complete, destruction of tumors as well as regeneration of epithelium were observed after the treatment. In conclusion, Ho-166 patch is a useful treatment modality in superficial skin cancers. 10 refs., 4 tabs., 4 figs. (author)

Skin Cancer Awareness and Sun Protection Behavior Before and Following Treatment Among Skin Cancer-Treated Patients.

Science.gov (United States)

Abedini, Robabeh; Nasimi, Maryam; Nourmohammad Pour, Pedram; Etesami, Ifa; Al-Asiri, Safa; Tohidinik, Hamid Reza

2017-11-15

There is little known about illness perception in patients with skin tumors. We conducted this study to investigate Iranian patients' understanding of skin tumors, and to evaluate their sun-protective behavior changes after treatment of skin cancer. Patients with a skin biopsy of basal cell carcinoma were asked to complete questionnaires. A total of 110 patients were enrolled in the study. Patients were mostly referred to our tumor clinic from rural areas. At the skin cancer perception investigation, 63% of patients did not consider their disease as a long-lasting situation. Besides, 45.4% of patients consider their illness as a serious condition which significantly affecting their lives. Our patients had a strong belief in treatment control (81%) and 81% of them also described worries about their skin cancer. The leading causes of skin cancer as assumed by patients were: history of skin cancer (37.4%), poor medical care in the past (36.4%), extreme sun exposure (31.5%), and lack of sun protection (27.5%). In regard to sun-protective behavior after treatment of skin cancer, 55.4% of patients showed no changes or even negative change in their sun-protective behavior, But 44.5% of the patients changed their sun-protective behavior in a positive way which was statically significant (P ≤ 0.001). Our study demonstrates how our patients with skin cancer perceive their disease and we need to educate our patients, considering diseases' aspects, causes and symptoms. This is of great value as dermatologists should be aware of patients' perceptions of their disease in order to improve patients' knowledge through educating more about different aspects of disease.

Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

Science.gov (United States)

Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

2015-07-01

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells.

Directory of Open Access Journals (Sweden)

Sungeun Kim

Full Text Available Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic potential, self-renewal, heterogeneous differentiation, and bipotency. Gene expression analysis and immunostaining of TICs and non-TICs revealed that FGFR2 was preferentially expressed in TICs. Loss of FGFR2 impaired self-renewal of TICs, thus resulting in marked decreases in the TIC population and tumorigenic potential. Restoration of FGFR2 rescued the defects in TIC pool maintenance, bipotency, and breast tumor growth driven by FGFR2 knockdown. In addition, pharmacological inhibition of FGFR2 kinase activity led to a decrease in the TIC population which resulted in suppression of breast tumor growth. Moreover, human breast TICs isolated from patient tumor samples were found enriched in a FGFR2+ population that was sufficient to initiate tumor growth. Our data suggest that FGFR2 is essential in sustaining the breast TIC pool through promotion of self-renewal and maintenance of bipotent TICs, and raise the possibility of FGFR2 inhibition as a strategy for anti-cancer therapy by eradicating breast TICs.

Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening.

Science.gov (United States)

Christensen, Anne G; Ehmsen, Sidse; Terp, Mikkel G; Batra, Richa; Alcaraz, Nicolas; Baumbach, Jan; Noer, Julie B; Moreira, José; Leth-Larsen, Rikke; Larsen, Martin R; Ditzel, Henrik J

2017-08-01

A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics. Within these pairs, one, but not the other, resulted in tumors in immunodeficient NOD/Shi-scid/IL-2 Rγ null mice and efficiently formed mammospheres. Quantitative proteomics and phosphoproteomics were used to map signaling pathways associated with the tumor-initiating ability. Signaling associated with apoptosis was suppressed in tumor-initiating versus nontumorigenic counterparts with pro-apoptotic proteins, such as Bcl2-associated agonist of cell death (BAD), FAS-associated death domain protein (FADD), and myeloid differentiation primary response protein (MYD88), downregulated in tumor-initiating epithelial-like cells. Functional studies confirmed significantly lower apoptosis in tumor-initiating versus nontumorigenic cells. Moreover, central pathways, including β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signaling, exhibited increased activation in the tumor-initiating cells. To evaluate the CSC model as a tool for drug screening, we assessed the effect of separately blocking NF-κB and Wnt/β-catenin signaling and found markedly reduced mammosphere formation, particularly for tumor-initiating cells. Similar reduction was also observed using patient-derived primary cancer cells. Furthermore, blocking NF-κB signaling in mice transplanted with tumor-initiating cells significantly reduced tumor outgrowth. Our study demonstrates that suppressed apoptosis, activation

Re-irradiation for abdominal tumor. Preliminary results

International Nuclear Information System (INIS)

Narisada, Hiroyuki; Imada, Hajime; Tomoda, Yoshinori

2012-01-01

The purpose of this study was to assess the efficacy of loco-regional radiotherapy for recurrent abdominal tumor treated with re-irradiation. Re-irradiated areas of 16 patients were eight of pelvic space, five of retroperitonium and three of liver or porta hepatica. Eligibility criteria of re-irradiation were success of initial irradiation, no other effective treatment except re-irradiation, constancy of bowel gas at hunger status and respiratory movement, visceral dosage reduction at re-irradiation. Total dose of initial, second course of radiation were 51.3±10.8 Gy, 50.6±14.2 Gy, respectively. Interval of initial and second course of radiation were 16.6±10.2 months. Local control after second course of radiation was four cases of complete response, five of partial response and seven of stable disease. Median survival periods were 55 months after initial treatment and 28 months after second course of radiation. In two cases of pelvic reirradiation, skin to pelvic space fistula was occurred. Re-irradiation for abdominal tumor may become useful salvage treatment. (author)

Impact of initial tumor volume on radiotherapy outcome in patients with T2 glottic cancer

International Nuclear Information System (INIS)

Rutkowski, T.

2014-01-01

The aim of this study was to quantify the impact of initial tumor volume (TV) on radiotherapy (RT) outcome in patients with T2 glottic cancer. Initial TV was calculated for 115 consecutive patients with T2 glottic cancer who had been treated with definitive RT alone at a single institution. The results showed strong correlations of TV with 3-year local tumor control (LTC) and disease-free survival (DFS). For TV ≤ 0.7 cm 3 , 3-year LTC was 83 %; for TV 0.7-3.6 cm 3 this was 70 % and for TV 3.6-17 cm 3 44 %. Analysis of total dose vs. initial TV showed that larger T2 glottic tumors with a TV of around 5 cm 3 (2-2.5 cm in diameter with 10 10 cancer cells) need an extra 6.5 Gy to achieve similar 3-year LTC rates as for small tumors with a TV of 0.5 cm 3 (∝1 cm in diameter with 10 9 cancer cells). Although classification of tumors according to TV cannot replace TNM staging in daily practice, it could represent a valuable numerical supplement for planning the optimal dose fractionation scheme for individual patients. (orig.)

MR imaging-guided percutaneous cryotherapy for lung tumors: initial experience.

Science.gov (United States)

Liu, Shangang; Ren, Ruimei; Liu, Ming; Lv, Yubo; Li, Bin; Li, Chengli

2014-09-01

To evaluate prospectively the initial clinical experience of magnetic resonance (MR) imaging-guided percutaneous cryotherapy of lung tumors. MR imaging-guided percutaneous cryotherapy was performed in 21 patients with biopsy-proven lung tumors (12 men, 9 women; age range, 39-79 y). Follow-up consisted of contrast-enhanced chest computed tomography (CT) scan performed at 3-month intervals to assess tumor control; CT scanning was carried out for 12 months or until death. Cryotherapy procedures were successfully completed in all 21 patients. Pneumothorax occurred in 7 (33.3%) of 21 patients. Chest tube placement was required in one (4.8%) case. Hemoptysis was exhibited by 11 (52.4%) patients, and pleural effusion occurred in 6 (28.6%) patients. Other complications were observed in 14 (66.7%) patients. The mean follow-up period was 10.5 months (range, 9-12 mo) in patients who died. At month 12 of follow-up, 7 (33.3%) patients had a complete response to therapy, and 10 (47.6%) patients showed a partial response. In addition, two patients had stable disease, and two patients developed progressive disease; one patient developed a tumor in the liver, and the other developed a tumor in the brain. The 1-year local control rate was 81%, and 1-year survival rate was 90.5%. MR imaging-guided percutaneous cryotherapy appears feasible, effective, and minimally invasive for lung tumors. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Radionuclide therapy of skin cancers and Bowen's disease using specially designed skin patch: A pilot study in an animal model and clinical trial

International Nuclear Information System (INIS)

Lee, J. D.; Park, K. K.; Lee, M. G.; Lee, J. T.; Yoo, H. S.; Kim, E. H.; Rhim, K. J.; Kim, Y. M.; Park, K. B.; Kim, J. R.

1997-01-01

Skin cancer is the most common malignant tumors in human. Therapeutic modalities of the skin cancers are local destruction, radiotherapy and surgery. External radiation therapy leads to good results, however, overall 5-6 weeks of treatment period is needed to deliver optimal radiation dose to tumors. In this study, β-emitting radionuclide, Ho-166, impregnated in a specially designed patch was utilized to superficial skin cancers and Bowen's disease for local irradiation. Methods; Animal study was employed in 10 mice with chemically induced skin tumors. Five- mm size patches containing 22.2 -72.15 MBq(0.6 - 1.95 mCi) of Ho-166 were applied to the tumor surface for 1 -2 hr. In clinical trial, patients with squamous carcinoma(n=3), basal cell carcinoma(n=1), and Bowen's disease(n=1) were treated with patches containing 273.8 - 999 MBq (7.4 - 27 mCi) of Ho-166 for 30 minutes to 1 hour. Pathologic examination was performed 4 - 7 weeks after the treatment in animal model. Skin biopsy was performed 8 weeks post-treatment in four patients. Results; Tumor destruction was seen 1 week post the treatment, however, radiation dermatitis or ulceration developed at the site of radionuclide application. Those reactions healed gradually with fibrosis or epithelialization, which was confirmed pathologically. No significant adverse reaction to radiation except subcutaneous fibrosis was found. Conclusion; Superficial skin tumors could be successfully treated by topical application of β-emitting radionuclides. (author)

Rac1 is crucial for Ras-dependent skin tumor formation by controlling Pak1-Mek-Erk hyperactivation and hyperproliferation in vivo

DEFF Research Database (Denmark)

Wang, Z; Pedersen, Esben Ditlev Kølle; Basse, A

2010-01-01

that Rac1 is essential for DMBA/TPA-induced skin tumor formation. This corresponded to a decreased keratinocyte hyperproliferation, although apoptosis was not detectably altered. Activated Rac1 promoted Erk-dependent hyperproliferation by Pak1-mediated Mek activation independent of Mek1 phosporylation...

Merkel cell tumor of the skin treated with localized radiotherapy: are widely negative margins required?

Directory of Open Access Journals (Sweden)

David Parda

2011-03-01

Full Text Available Merkel’s cell carcinoma is a rare cutaneous tumor that can affect a wide variety of sites throughout the body. Commonly, it affects the skin alone and the management of limited disease can be confusing since the natural history of the disease involves distant metastasis. Traditional management has required wide local excision with negative margins of resection. We describe a case treated with local therapy alone and review the literature to suggest that complete microscopic excision may not be required if adjuvant radiotherapy is used.

Role of chemical carcinogens in epithelial and mesenchymal neoplasms with tumor initiation-promotion protocol and the effect of 13-cis retinoic acid in chemo prevention

International Nuclear Information System (INIS)

Bukhari, S.M.H.; Shahzad, S.Q.; Naeem, S.; Qureshi, G.R.; Naveed, I.A.

2002-01-01

Objective: To study the effects of chemical carcinogens on epithelial and mesenchymal tumorigenesis with tumor initiation-promotion protocol and the use of 13-cis retinoic acid as a chemo preventive agent. Design: It was an experimental study. Place and Duration of Study: The study was conducted at Postgraduate Medical Institute (PGML) Lahore for 20 weeks. Materials and Methods: Sixty albino rats were divided into six groups of ten of animals each. First group of animals (control) was not given carcinogens and 13-cis retinoic acid in second group DMBA was applied on the dorsal skin in repeated dos of 100 mu g/ml in acetone, twice a weak. In the third group DMBA was given 100 mu g/ml as single dose while TPA was given 10 mu g//ml in acetone, twice a weak after two weeks of DMBA applications. In fourth group only DMBA 100 mu g/ml in acetone was applied as a single dose. In fifth and sixth groups 13-cis retinoic acid was given topically before and after the application of DMBA and TPA. Results: First and fourth groups did not develop any tumor. In second groups 2 animals developed malignant fibrous histiocytoma, 4 squamous cell carcinoma while 1 dysphasia and 1 carcinoma in situ. Third group developed osteoma (3 animals), papilloma (3 animals, squamous cell carcinoma (01) and dysplasia (01). Conclusion: Our results showed that DMBA acts as tumor initiator while TPA as promoter. DMBA also produces tumors itself when given alone in repeated doses. The chemical carcinogens are not only a cause of epithelial carcinogenesis but also responsible for mesenchymal tumorigenesis. 13 cis retinoic acid was equally effective in both stages of tumorigenesis. It also prevents malignant conversion of chemically induced benign tumors. (author)

BMI-1 targeting interferes with patient-derived tumor-initiating cell survival and tumor growth in prostate cancer

Science.gov (United States)

Yusuff, Shamila; Davis, Stephani; Flaherty, Kathleen; Huselid, Eric; Patrizii, Michele; Jones, Daniel; Cao, Liangxian; Sydorenko, Nadiya; Moon, Young-Choon; Zhong, Hua; Medina, Daniel J.; Kerrigan, John; Stein, Mark N.; Kim, Isaac Y.; Davis, Thomas W.; DiPaola, Robert S.; Bertino, Joseph R.; Sabaawy, Hatem E.

2016-01-01

Purpose Current prostate cancer (PCa) management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy-resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TICs-tailored therapies appears to be a promising approach. Experimental design We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient derived prostate cancer cells and xenograft models to characterize the effects of pharmacological inhibitors of BMI-1. Results We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacological inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor (AR)-directed therapies, without toxic effects on normal tissues. Conclusions Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective PCa treatment. PMID:27307599

UV-induced skin damage

International Nuclear Information System (INIS)

Ichihashi, M.; Ueda, M.; Budiyanto, A.; Bito, T.; Oka, M.; Fukunaga, M.; Tsuru, K.; Horikawa, T.

2003-01-01

Solar radiation induces acute and chronic reactions in human and animal skin. Chronic repeated exposures are the primary cause of benign and malignant skin tumors, including malignant melanoma. Among types of solar radiation, ultraviolet B (290-320 nm) radiation is highly mutagenic and carcinogenic in animal experiments compared to ultraviolet A (320-400 nm) radiation. Epidemiological studies suggest that solar UV radiation is responsible for skin tumor development via gene mutations and immunosuppression, and possibly for photoaging. In this review, recent understanding of DNA damage caused by direct UV radiation and by indirect stress via reactive oxygen species (ROS) and DNA repair mechanisms, particularly nucleotide excision repair of human cells, are discussed. In addition, mutations induced by solar UV radiation in p53, ras and patched genes of non-melanoma skin cancer cells, and the role of ROS as both a promoter in UV-carcinogenesis and an inducer of UV-apoptosis, are described based primarily on the findings reported during the last decade. Furthermore, the effect of UV on immunological reaction in the skin is discussed. Finally, possible prevention of UV-induced skin cancer by feeding or topical use of antioxidants, such as polyphenols, vitamin C, and vitamin E, is discussed

Cellular and molecular events leading to the development of skin cancer

International Nuclear Information System (INIS)

Melnikova, Vladislava O.; Ananthaswamy, Honnavara N.

2005-01-01

The transition from a normal cell to a neoplastic cell is a complex process and involves both genetic and epigenetic changes. The process of carcinogenesis begins when the DNA is damaged, which then leads to a cascade of events leading to the development of a tumor. Ultraviolet (UV) radiation causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. Upon DNA damage, the p53 tumor suppressor protein undergoes phosphorylation and translocation to the nucleus and aids in DNA repair or causes apoptosis. Excessive UV exposure overwhelms DNA repair mechanisms leading to induction of p53 mutations and loss of Fas-FasL interaction. Keratinocytes carrying p53 mutations acquire a growth advantage by virtue of their increased resistance to apoptosis. Thus, resistance to cell death is a key event in photocarcinogenesis and conversely, elimination of cells containing excessive UV-induced DNA damage is a key step in protecting against skin cancer development. Apoptosis-resistant keratinocytes undergo clonal expansion that eventually leads to formation of actinic keratoses and squamous cell carcinomas. In this article, we will review some of the cellular and molecular mechanisms involved in initiation and progression of UV-induced skin cancer

Cellular and molecular events leading to the development of skin cancer

Energy Technology Data Exchange (ETDEWEB)

Melnikova, Vladislava O. [Department of Immunology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Unit 902, Houston, TX 77030 (United States); Ananthaswamy, Honnavara N. [Department of Immunology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Unit 902, Houston, TX 77030 (United States)]. E-mail: hanantha@mdanderson.org

2005-04-01

The transition from a normal cell to a neoplastic cell is a complex process and involves both genetic and epigenetic changes. The process of carcinogenesis begins when the DNA is damaged, which then leads to a cascade of events leading to the development of a tumor. Ultraviolet (UV) radiation causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. Upon DNA damage, the p53 tumor suppressor protein undergoes phosphorylation and translocation to the nucleus and aids in DNA repair or causes apoptosis. Excessive UV exposure overwhelms DNA repair mechanisms leading to induction of p53 mutations and loss of Fas-FasL interaction. Keratinocytes carrying p53 mutations acquire a growth advantage by virtue of their increased resistance to apoptosis. Thus, resistance to cell death is a key event in photocarcinogenesis and conversely, elimination of cells containing excessive UV-induced DNA damage is a key step in protecting against skin cancer development. Apoptosis-resistant keratinocytes undergo clonal expansion that eventually leads to formation of actinic keratoses and squamous cell carcinomas. In this article, we will review some of the cellular and molecular mechanisms involved in initiation and progression of UV-induced skin cancer.

Cell-type-specific roles for COX-2 in UVB-induced skin cancer

Science.gov (United States)

Herschman, Harvey

2014-01-01

In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

Gene expression in skin tumors induced in hairless mice by chronic exposure to ultraviolet B irradiation

International Nuclear Information System (INIS)

Sato, Hiromi; Tanaka, Misao; Kobayashi, Shizuko; Suzuki, Junko S.; Ogiso, Manabu; Tohyama, Chiharu

1997-01-01

We investigated the expressions of c-Ha-ras, c-jun, c-fos, c-myc genes and p53 protein in the development of skin tumours induced by chronic exposure to UVB without a photosensitizer using hairless mice. When mice were exposed to UVB at a dose of 2 kJ/m 2 three times a week, increased c-Ha-ras and c-myc transcripts were detected after only 5 weeks of exposure, while no tumour appeared on the exposed skin. The increase in gene expression continued until 25 weeks, when tumours, identified pathologically as mainly squamous cell carcinomas (SCC), developed in the dorsal skin. In these SCC, overexpression of c-fos mRNA was also observed along with the increases in c-Ha-ras and c-myc. A single dose of UVB (2 kJ/m 2 ) applied to the backs of hairless mice transiently induced overexpression of the early event genes c-fos, c-jun and c-myc, but not c-Ha-ras, in the exposed area of skin. Accumulation of p53 protein was determined by Western blotting analysis of immunohistochemistry using monoclonal antibodies PAb 240 or 246, which recognize mutant or wide type, respectively. In the SCC, a mutant p53 protein accumulated in the cytoplasm and nucleus. After single-dose irradiation, the increased wild-type p53 protein was observed in the nuclei of epidermal cells. The present results suggest that overexpression of the c-fos, c-myc and c-Ha-ras genes, and the mutational changes in p53 protein might be associated with skin photocarcinogenesis. Moreover, overexpression of the c-Ha-ras and c-myc genes might be an early event in the development of UVB-induced skin tumors in mice. (author)

Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes

International Nuclear Information System (INIS)

Kilkenny, A.E.; Morgan, D.; Spangler, E.F.; Yuspa, S.H.

1985-01-01

The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents

Tumor scintigraphy by the method for subtracting the initial image with technetium-99m labeled antibody

International Nuclear Information System (INIS)

Karube, Yoshiharu; Katsuno, Kentaro; Ito, Sanae; Matsunaga, Kazuhisa; Takata, Jiro; Kuroki, Masahide; Murakami, Masaaki; Matsuoka, Yuji

1999-01-01

The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value. (author)

β-HPV Infection Correlates with Early Stages of Carcinogenesis in Skin Tumors and Patient-Derived Xenografts from a Kidney Transplant Recipient Cohort.

Science.gov (United States)

Borgogna, Cinzia; Olivero, Carlotta; Lanfredini, Simone; Calati, Federica; De Andrea, Marco; Zavattaro, Elisa; Savoia, Paola; Trisolini, Elena; Boldorini, Renzo; Patel, Girish K; Gariglio, Marisa

2018-01-01

Many malignancies that occur in high excess in kidney transplant recipients (KTRs) are due to viruses that thrive in the setting of immunosuppression. Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR, has been associated with skin infection by human papillomavirus (HPV) from the beta genus. In this report, we extend our previous investigation aimed at identifying the presence of active β-HPV infection in skin tumors from KTRs through detection of viral protein expression. Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize infection in five tumors [one keratoacanthoma (KA), three actinic keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from two patients who had been both transplanted twice, had developed multiple KCs, and presented with a long history of immunosuppression (>30 years). These infected tissues displayed intraepidermal hyperplasia and increased expression of the ΔNp63 protein, which extended into the upper epithelial layers. In addition, using a xenograft model system in nude mice displaying a humanized stromal bed in the site of grafting, we successfully engrafted three AKs, two of which were derived from the aforementioned KTRs and displayed β-HPV infection in the original tumor. Of note, one AK-derived xenograft, along with its ensuing lymph node metastasis, was diagnosed as squamous cell carcinoma (SCC). In the latter, both β-HPV infection and ΔNp63 expression were no longer detectable. Although the overall success rate of engrafting was very low, the results of this study show for the first time that β-HPV + and ΔNp63 + intraepidermal hyperplasia can indeed progress to an aggressive SCC able to metastasize. Consistent with a series of reports attributing a causative role of β-HPV at early stages of skin carcinogenesis through ΔNp63 induction and increased keratinocytes stemness, here we provide in vivo evidence that

Evaluation of the contribution of chronic skin irritation and selected compositional parameters to the tumorigenicity of petroleum middle distillates in mouse skin.

Science.gov (United States)

Freeman, J J; Federici, T M; McKee, R H

1993-07-28

Two-year skin carcinogenicity studies were conducted in C3H mice to assess the effects of irritation and selected compositional parameters on the carcinogenic potential of four petroleum liquids. Three samples (lightly refined paraffinic oil, LRPO; lightly hydrodesulfurized specialty oil, LHSO; jet fuel, JF) can be generically classified as middle distillates, i.e. distillation occurs between 350 and 700 degrees F (175-370 degrees C). The fourth sample was a Steam Cracked Gas Oil (SCGO) that distilled within the same range. In studies that assess the effects of irritation on tumorigenicity, LRPO was tested undiluted or was diluted to 50% and 25% in either mineral oil (which eliminated irritation of the skin) or toluene (which did not). Undiluted LRPO elicited tumors in 8% of the mice. Both dilution procedures eliminated tumorigenic potential. Thus, it was possible to maintain a visible level of skin irritation equivalent to that elicited by undiluted LRPO without inducing tumors. SCGO elicited a chronic irritant state grossly equivalent to LRPO but was not tumorigenic. Jet Fuel A (JF) was tested undiluted using both a standard skin painting protocol and an intermittent dosing schedule in which treatment was suspended periodically to allow skin irritation to resolve. The standard treatment protocol of JF resulted in both marked skin irritation and tumors in 44% of the mice. However, using the intermittent schedule, the tumor yield was reduced to 2%. Collectively these data demonstrate that tumor formation is not a necessary sequelae to chronic skin irritation. Conversely, prevention of a marked chronic irritant state was accompanied by decreased tumor yield. These data suggest that the chronic irritant state may be a necessary but not sufficient condition for tumor formation. In studies to assess the effects of compositional parameters, a lightly hydrodesulfurized specialty oil (LHSO) similar to LRPO but refined to have negligible levels of sulfur compounds (3 ppm

Initiative action of tumor-associated macrophage during tumor metastasis

Directory of Open Access Journals (Sweden)

Saroj Singh

2017-06-01

In this review article, we present an overview of mechanisms responsible for TAMs recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. We describe the interplay between Th17 cells and other immune cells in the tumor microenvironment, and we assess both the potential antitumorigenic and pro-tumorigenic activities of Th17 cells and their associated cytokines. Understanding the nature of Th17 cell responses in the tumor microenvironment will be important for the design of more efficacious cancer immunotherapies. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

Investigation of pion-treated human skin nodules for therapeutic gain

International Nuclear Information System (INIS)

Kligerman, M.M.; Sala, J.M.; Wilson, S.; Yuhas, J.M.

1978-01-01

A patient with multiple metastatic tumor nodules in the skin, from a primary breast carcinoma, was treated with graded doses of pions and x rays to establish skin tolerance. She was followed up for 346 days, permitting observation of time to regrowth of the tumor nodules. All 16 of these had disappeared after treatment, without significant correlation with type of radiation or dose, or with nodule size. However, time to regrowth depended both on the type and the dose of radiation. Earlier, relative biological effectiveness (RBE), was established at 1.42 for acute skin injury. Using this RBE to normalize doses of pions and x rays causing equivalent acute skin injury, and plotting those doses vs time to regrowth of tumor nodules, yielded a therapeutic gain (37.5%) in favor of pions. No late skin or subcutaneous tissue changes were seen, and no qualitative difference between pions and x rays in late skin effects was observed

The Danish Nonmelanoma Skin Cancer Dermatology Database.

Science.gov (United States)

Lamberg, Anna Lei; Sølvsten, Henrik; Lei, Ulrikke; Vinding, Gabrielle Randskov; Stender, Ida Marie; Jemec, Gregor Borut Ernst; Vestergaard, Tine; Thormann, Henrik; Hædersdal, Merete; Dam, Tomas Norman; Olesen, Anne Braae

2016-01-01

The Danish Nonmelanoma Skin Cancer Dermatology Database was established in 2008. The aim of this database was to collect data on nonmelanoma skin cancer (NMSC) treatment and improve its treatment in Denmark. NMSC is the most common malignancy in the western countries and represents a significant challenge in terms of public health management and health care costs. However, high-quality epidemiological and treatment data on NMSC are sparse. The NMSC database includes patients with the following skin tumors: basal cell carcinoma (BCC), squamous cell carcinoma, Bowen's disease, and keratoacanthoma diagnosed by the participating office-based dermatologists in Denmark. Clinical and histological diagnoses, BCC subtype, localization, size, skin cancer history, skin phototype, and evidence of metastases and treatment modality are the main variables in the NMSC database. Information on recurrence, cosmetic results, and complications are registered at two follow-up visits at 3 months (between 0 and 6 months) and 12 months (between 6 and 15 months) after treatment. In 2014, 11,522 patients with 17,575 tumors were registered in the database. Of tumors with a histological diagnosis, 13,571 were BCCs, 840 squamous cell carcinomas, 504 Bowen's disease, and 173 keratoakanthomas. The NMSC database encompasses detailed information on the type of tumor, a variety of prognostic factors, treatment modalities, and outcomes after treatment. The database has revealed that overall, the quality of care of NMSC in Danish dermatological clinics is high, and the database provides the necessary data for continuous quality assurance.

Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

Science.gov (United States)

Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

2015-10-01

Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

Human cell transformation in the study of sunlight-induced cancers in the skin of man

International Nuclear Information System (INIS)

Sutherland, B.M.; Bennett, P.V.

1988-01-01

Human cell transformation provides a powerful approach to understanding - at the cellular and molecular levels - induction of cancers in the skin of man. A principal approach to this problem is the direct transformation of human skin cells by exposure to ultraviolet and/or near-UV radiation. The frequency of human cells transformed to anchorage independence increases with radiation exposure; the relative transforming efficiencies of different wavelengths implies that direct absorption by nucleic acids is a primary initial event. Partial reversal of potential transforming lesions by photoreactivation suggests that pyrimidine dimers, as well as other lesions, are important in UV transformation of human cells. Human cells can also be transformed by transfection with cloned oncogenes, or with DNAs from tumors or tumor cell lines. Cells treated by the transfection procedure (but without DNA) or cells transfected with DNAs from normal mammalian cells or tissues show only background levels of transformation. Human cells can be transformed to anchorage-independent growth by DNAs ineffective in transformation of NIH 3T3 cells (including most human skin cancers), permitting the analysis of oncogenic molecular changes even in tumor DNAs difficult or impossible to analyze in rodent cell systems. 29 refs.; 4 figs.; 1 table

Two-step Raman spectroscopy method for tumor diagnosis

Science.gov (United States)

Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Two-step Raman spectroscopy phase method was proposed for differential diagnosis of malignant tumor in skin and lung tissue. It includes detection of malignant tumor in healthy tissue on first step with identification of concrete cancer type on the second step. Proposed phase method analyze spectral intensity alteration in 1300-1340 and 1640-1680 cm-1 Raman bands in relation to the intensity of the 1450 cm-1 band on first step, and relative differences between RS intensities for tumor area and healthy skin closely adjacent to the lesion on the second step. It was tested more than 40 ex vivo samples of lung tissue and more than 50 in vivo skin tumors. Linear Discriminant Analysis, Quadratic Discriminant Analysis and Support Vector Machine were used for tumors type classification on phase planes. It is shown that two-step phase method allows to reach 88.9% sensitivity and 87.8% specificity for malignant melanoma diagnosis (skin cancer); 100% sensitivity and 81.5% specificity for adenocarcinoma diagnosis (lung cancer); 90.9% sensitivity and 77.8% specificity for squamous cell carcinoma diagnosis (lung cancer).

Fractionated laser resurfacing corrects the inappropriate UVB response in geriatric skin

OpenAIRE

Spandau, Dan F; Lewis, Davina A.; Somani, Ally-Khan; Travers, Jeffrey B.

2012-01-01

Non-melanoma skin cancer is a disease primarily afflicting geriatric patients as evidenced by the fact that 80% of all non-melanoma skin cancers are diagnosed in patients over the age of 60 years. As such, geriatric skin responds to cancer-inducing UVB irradiation in a manner that allows the establishment of tumor cells. Currently, the only effective treatment for non-melanoma skin cancer is the removal of the tumors after they appear, indicating the need for a more cost-effective prophylacti...

Tumor-initiating CD49f cells are a hallmark of chemoresistant triple negative breast cancer.

Science.gov (United States)

Gomez-Miragaya, Jorge; González-Suárez, Eva

2017-01-01

Taxanes are mainstay treatment of triple negative breast cancer (TNBC) patients but resistance often develops. Using TNBC patient-derived orthoxenografts (PDX) we have recently discovered that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands in tumors that have acquired resistance. Importantly, sensitivity to taxanes is recovered after long-term drug interruption. The characterization of this chemoresistant CD49f+ cells provides a unique opportunity to identify novel targets for the treatment of chemoresistant TNBC.

High initiation and long duration of breastfeeding despite absence of early skin-to-skin contact in Karen refugees on the Thai-Myanmar border: a mixed methods study.

Science.gov (United States)

White, Adrienne L; Carrara, Verena I; Paw, Moo Kho; Malika; Dahbu, Colleypaw; Gross, Mechthild M; Stuetz, Wolfgang; Nosten, Francois H; McGready, Rose

2012-12-13

Early skin-to-skin contact (SSC) after birth is recommended as part of the United Nations Children's Fund (UNICEF) baby friendly health initiative to promote optimum breastfeeding. This paper reports rates of breastfeeding initiation and duration in a low resource environment, where early SSC is not practised, and explores views of pregnant women and midwives surrounding breastfeeding and swaddling. Data from records from a single hospital on the Thai-Myanmar border where refugee women gave birth during a one-year period (2010) were used to determine breastfeeding initiation rates and the time of the first breastfeed, and duration of breastfeeding of the previous alive child in multigravidae. Focus group discussions (FGD) were conducted to obtain information from pregnant women attending antenatal care about their intended or previous duration of breastfeeding and views on breastfeeding. Interviews with local midwives explored reasons for high rates of breastfeeding in this setting and the practice of newborn swaddling. Of 1404 live births in 2010 in Maela refugee camp there were 982 evaluable mother-newborn pairs, including 80 infants born before 37 weeks gestation. Initiation of breastfeeding within the first hour after birth and exclusive breastfeeding at discharge in term mother-newborn pairs was 91.2% (823/902) and 99.3% (896/902); and before 37 weeks gestation, 48.8% (39/80) and 98.8% (79/80). Reported duration of previous breastfeeding was 19 (range 2 to 72) months.During FGD all primigravidae (n = 17) intended to breastfeed and all multigravidae (n = 33) had previously breastfed; expected or previous duration of feeding was for more than one year or longer. The major theme identified during FGD was breastfeeding is "good". Women stated their intention to breastfeed with certainty. This certainty was echoed during the interviews with midwifery staff. SSC requires a delay in early swaddling that in Karen people, with animistic beliefs, could risk loss

TIG3 tumor suppressor-dependent organelle redistribution and apoptosis in skin cancer cells.

Directory of Open Access Journals (Sweden)

Tiffany M Scharadin

Full Text Available TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It is also important in cancer, as TIG3 level is reduced in tumors and in skin cancer cell lines, suggesting that loss of expression may be required for cancer cell survival. An important goal is identifying how TIG3 limits cell survival. In the present study we show that TIG3 expression in epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and promotes morphological and biochemical apoptosis. To identify the mechanism that drives these changes, we demonstrate that TIG3 localizes near the centrosome and that pericentrosomal accumulation of TIG3 alters microtubule and microfilament organization and organelle distribution. Organelle accumulation at the centrosome is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal organelle accumulation. These changes are associated with reduced cyclin D1, cyclin E and cyclin A, and increased p21 level. In addition, Bax level is increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9 and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis.

The oncogenic action of ionizing radiation on rat skin

International Nuclear Information System (INIS)

Burns, F.J.

1991-01-01

Progress has occurred in several areas corresponding to the specific aims of the proposal: (1) Progression and multiple events in radiation carcinogenesis of rat skin as a function of LET; (2) cell cycle kinetics of irradiated rat epidermis as determined by double labeling and double emulsion autoradiography; (3) oncogene activation detected by in situ hybridization in radiation-induced rat skin tumors; (4) amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of LET; and (5) transformation of rat skin keratinocytes by ionizing radiation in combination with c-Ki-ras and c-myc oncogenes. 111 refs., 13 figs., 12 tabs

Influence of the Human Skin Tumor Type in Photodynamic Therapy Analysed by a Predictive Model

Directory of Open Access Journals (Sweden)

I. Salas-García

2012-01-01

Full Text Available Photodynamic Therapy (PDT modeling allows the prediction of the treatment results depending on the lesion properties, the photosensitizer distribution, or the optical source characteristics. We employ a predictive PDT model and apply it to different skin tumors. It takes into account optical radiation distribution, a nonhomogeneous topical photosensitizer spatial temporal distribution, and the time-dependent photochemical interaction. The predicted singlet oxygen molecular concentrations with varying optical irradiance are compared and could be directly related with the necrosis area. The results show a strong dependence on the particular lesion. This suggests the need to design optimal PDT treatment protocols adapted to the specific patient and lesion.

Liposomalization of oxaliplatin induces skin accumulation of it, but negligible skin toxicity.

Science.gov (United States)

Nishida, Kentaro; Kashiwagi, Misaki; Shiba, Shunsuke; Muroki, Kiwamu; Ohishi, Akihiro; Doi, Yusuke; Ando, Hidenori; Ishida, Tatsuhiro; Nagasawa, Kazuki

2017-12-15

Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil ® , Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP. However, whether Lipo-l-OHP causes HFS-like skin toxicity similar to Lipo-DXR remains to be determined. Administration of Lipo-l-OHP promoted accumulation of platinum in rat hind paws, however, it caused negligible morphological and histological alterations on the plantar surface of the paws. Administration of DiI-labeled empty PEGylated liposomes gave almost the same distribution profile of dyes into the dermis of hind paws with DXR as in the case of Lipo-DXR. Treatment with Lipo-l-OHP, Lipo-DXR, DiI-labeled empty PEGylated liposomes or empty PEGylated liposomes caused migration of CD68 + macrophages into the dermis of hind paws. These findings suggest that the skin toxicity on administration of liposomalized drugs is reflected in the proinflammatory characteristics of encapsulated drugs, and indicate that Lipo-l-OHP with a higher anti-cancer effect and no HFS may be an outstanding l-OHP preparation leading to an improved quality of life of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of a team intraoperative Radiation therapy and measurement of dose in skin with film radiochromic

International Nuclear Information System (INIS)

Onses Segarra, A.; Sancho Kolster, I.; Eraso Urien, A.; Pla Farnos, M. J.; Picon Olmos, C.

2015-01-01

This paper presents the results of the initial reference state of intraoperative radiotherapy equipment lntraBeam, for performing breast treatments are analyzed. To the initial reference team was established for the following dosimetric and geometric beam parameters: percentage depth dose, beam quality, isotropy, linearity and mechanical and geometric integrity for both the source RX as for different spherical applicators of the team. Based on these checks, a program of periodic quality control was established. One of the exclusion criteria for this treatment is that the tumor is less than l cm of the skin, yaque give doses received in this organ can be high. For this reason it is important to know exactly the absorbed dose in skin during these treatments. In this regard we have implemented a system for measuring the skin dose during treatment with Radiochromic film, placing 4 film segments in fixed positions of the skin around the surgical incision. It .ha obtained calibration curve of sterilized films and compared the results with a calibration beam megavoltage. The results of the skin dose measurements are compared with theoretical estimates given by the planning system equipment. The results indicate the need to measure individually the skin dose for these treatments. (Author)

Acute skin reactions observed in fractionated proton irradiation

International Nuclear Information System (INIS)

Arimoto, Takuro; Maruhashi, Noboru; Takada, Yoshihisa; Hayakawa, Yoshinori; Inada, Tetsuo; Kitagawa, Toshio

1989-01-01

Between May 1985 and July 1987, 49 skin reactions of 43 patients treated by proton irradiation were observed at the Particle Radiation Medical Science Center (PARMS), the University of Tsukuba. Taking the peak skin score as an endpoint, the radiobiological effects [relative biological effectiveness (RBE) and time-dose relationship] of the proton beam in multi-fractionated treatments were estimated. Factors influencing the skin dose, such as the prescribed tumor dose, tumor site, and number of applied fields, were also analyzed. The following conclusions regarding acute skin reactions to the clinical use of proton irradiation were obtained: 1) the physical skin-sparing effect of proton irradiation in single-field irradiation, especially in superficial regions, is not large compared with that of high-energy photon irradiation; 2) multidirectional proton irradiation significantly reduced the skin dose and severity of acute reasons; 3) the radiobiological effects of the proton beam, RBE and the time factor, estimated in human skin in multi-fractional treatment were slightly smaller than those of X-rays, i.e., 0.92 and -0.25±0.09, respectively. (author)

Tumor prevalence and biomarkers of genotoxicity in brown bullhead (Ameiurus nebulosus) in Chesapeake Bay tributaries

Energy Technology Data Exchange (ETDEWEB)

Pinkney, Alfred E., E-mail: Fred_Pinkney@fws.gov [U.S. Fish and Wildlife Service, Chesapeake Bay Field Office, 177 Admiral Cochrane Drive, Annapolis, MD 21401 (United States); Harshbarger, John C., E-mail: jcharshbarger@verizon.net [Department of Pathology, George Washington University Medical Center, 2300 I Street, NW, Washington, DC 20037 (United States); Karouna-Renier, Natalie K., E-mail: nkarouna@usgs.gov [U.S. Geological Survey, Patuxent Wildlife Research Center, BARC, Bldg. 308, Beltsville, MD 20705 (United States); Jenko, Kathryn [U.S. Geological Survey, Patuxent Wildlife Research Center, BARC, Bldg. 308, Beltsville, MD 20705 (United States); Balk, Lennart, E-mail: lennart.balk@itm.su.se [Department of Applied Environmental Science (ITM), Stockholm University SE-106 91, Stockholm (Sweden); Skarphe Latin-Small-Letter-Eth insdottir, Halldora; Liewenborg, Birgitta [Department of Applied Environmental Science (ITM), Stockholm University SE-106 91, Stockholm (Sweden); Rutter, Michael A., E-mail: mar36@psu.edu [Department of Mathematics, Penn State Erie, The Behrend College, 5091 Station Road, Erie, PA 16563 (United States)

2011-12-01

We surveyed four Chesapeake Bay tributaries for skin and liver tumors in brown bullhead (Ameiurus nebulosus). We focused on the South River, where the highest skin tumor prevalence (53%) in the Bay watershed had been reported. The objectives were to 1) compare tumor prevalence with nearby rivers (Severn and Rhode) and a more remote river (Choptank); 2) investigate associations between tumor prevalence and polynuclear aromatic hydrocarbons (PAHs) and alkylating agents; and 3) statistically analyze Chesapeake Bay bullhead tumor data from 1992 through 2008. All four South River collections exhibited high skin tumor prevalence (19% to 58%), whereas skin tumor prevalence was 2%, 10%, and 52% in the three Severn collections; 0% and 2% in the Choptank collections; and 5.6% in the Rhode collection. Liver tumor prevalence was 0% to 6% in all but one South River collection (20%) and 0% to 6% in the three other rivers. In a subset of samples, PAH-like biliary metabolites and {sup 32}P-DNA adducts were used as biomarkers of exposure and response to polycyclic aromatic compounds (PACs). Adducts from alkylating agents were detected as O6-methyl-2 Prime -deoxyguanosine (O6Me-dG) and O6-ethyl-2 Prime -deoxyguanosine (O6Et-dG) modified DNA. Bullheads from the contaminated Anacostia River were used as a positive control for DNA adducts. {sup 32}P-DNA adduct concentrations were significantly higher in Anacostia bullhead livers compared with the other rivers. We identified alkyl DNA adducts in bullhead livers from the South and Anacostia, but not the Choptank. Neither the PAH-like bile metabolite data, sediment PAH data, nor the DNA adduct data suggest an association between liver or skin tumor prevalence and exposure to PACs or alkylating agents in the South, Choptank, Severn, or Rhode rivers. Logistic regression analysis of the Chesapeake Bay database revealed that sex and length were significant covariates for liver tumors and length was a significant covariate for skin tumors

Tumor prevalence and biomarkers of genotoxicity in brown bullhead (Ameiurus nebulosus) in Chesapeake Bay tributaries

International Nuclear Information System (INIS)

Pinkney, Alfred E.; Harshbarger, John C.; Karouna-Renier, Natalie K.; Jenko, Kathryn; Balk, Lennart; Skarphéðinsdóttir, Halldóra; Liewenborg, Birgitta; Rutter, Michael A.

2011-01-01

We surveyed four Chesapeake Bay tributaries for skin and liver tumors in brown bullhead (Ameiurus nebulosus). We focused on the South River, where the highest skin tumor prevalence (53%) in the Bay watershed had been reported. The objectives were to 1) compare tumor prevalence with nearby rivers (Severn and Rhode) and a more remote river (Choptank); 2) investigate associations between tumor prevalence and polynuclear aromatic hydrocarbons (PAHs) and alkylating agents; and 3) statistically analyze Chesapeake Bay bullhead tumor data from 1992 through 2008. All four South River collections exhibited high skin tumor prevalence (19% to 58%), whereas skin tumor prevalence was 2%, 10%, and 52% in the three Severn collections; 0% and 2% in the Choptank collections; and 5.6% in the Rhode collection. Liver tumor prevalence was 0% to 6% in all but one South River collection (20%) and 0% to 6% in the three other rivers. In a subset of samples, PAH-like biliary metabolites and 32 P-DNA adducts were used as biomarkers of exposure and response to polycyclic aromatic compounds (PACs). Adducts from alkylating agents were detected as O6-methyl-2′-deoxyguanosine (O6Me-dG) and O6-ethyl-2′-deoxyguanosine (O6Et-dG) modified DNA. Bullheads from the contaminated Anacostia River were used as a positive control for DNA adducts. 32 P-DNA adduct concentrations were significantly higher in Anacostia bullhead livers compared with the other rivers. We identified alkyl DNA adducts in bullhead livers from the South and Anacostia, but not the Choptank. Neither the PAH-like bile metabolite data, sediment PAH data, nor the DNA adduct data suggest an association between liver or skin tumor prevalence and exposure to PACs or alkylating agents in the South, Choptank, Severn, or Rhode rivers. Logistic regression analysis of the Chesapeake Bay database revealed that sex and length were significant covariates for liver tumors and length was a significant covariate for skin tumors. - Highlights: ► We

SU-F-T-189: Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

International Nuclear Information System (INIS)

Takao, S; Matsuzaki, Y; Matsuura, T; Umegaki, K; Fujii, Y; Fujii, T; Katoh, N; Shimizu, S; Shirato, H

2016-01-01

Purpose: Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. Methods: The applicator composed of a combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). Results: The target heterogeneity index (HI = D_5/D_9_5) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. Conclusion: It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.

SU-F-T-189: Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

Energy Technology Data Exchange (ETDEWEB)

Takao, S; Matsuzaki, Y [Proton Beam Therapy Center, Hokkaido University Hospital, Sapporo, Hokkaido (Japan); Matsuura, T; Umegaki, K [Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido (Japan); Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido (Japan); Fujii, Y; Fujii, T [Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido (Japan); Katoh, N [Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Hokkaido (Japan); Shimizu, S; Shirato, H [Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido (Japan); Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido (Japan)

2016-06-15

Purpose: Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. Methods: The applicator composed of a combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). Results: The target heterogeneity index (HI = D{sub 5}/D{sub 95}) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. Conclusion: It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.

Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex.

Directory of Open Access Journals (Sweden)

Yanan Guo

Full Text Available Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1ccFsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis.

Role of stem cells in tumor initiation, metastasis formation and their use in cancer therapy

International Nuclear Information System (INIS)

Altaner, C.; Altanerova, V.

2010-01-01

This review considers recent advances in the stem cell field focusing on the challenges and opportunities for their use in clinical practice. Various kinds of stem cells and their roles in the human organism are in the review described. Attention is given to the role of mesenchymal stem cells as a potential tool in regenerative medicine. The origin and consequences of existence of tumor-initiating cells known as cancer stem cells is discussed also in context of metastasis formation. It seems that tumor-initiating cells might be responsible for resistance to many conventional cancer therapies, which might explain the limitations of these therapeutic modalities. Furthermore, the review focuses to tumor homing property of adult mesenchymal (stromal) stem cells. The feasibility of mesenchymal stem cells isolation from human adipose tissue, their genetic modifications with suicide genes together with ability to find tumor in the organism make them an attractive vehicle for cancer therapy without systemic toxicity. Published achievements from our laboratory in stem cell-based gene cancer therapy are shortly summarized. Generally, it is believed that the stem cell therapies might be ideal future treatment modality for inherited, degenerative diseases and in curing human malignancies as well. (author)

Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors

Directory of Open Access Journals (Sweden)

Shanawaz Mohammed Ghouse

2018-01-01

Full Text Available Summary: High numbers of mast cells populate the stroma of many types of neoplasms, including human papilloma virus-induced benign and malignant tumors in man and mouse. Equipped with numerous pattern recognition receptors and capable of executing important pro-inflammatory responses, mast cells are considered innate sentinels that significantly impact tumor biology. Mast cells were reported to promote human papilloma virus (HPV-induced epithelial hyperproliferation and neo-angiogenesis in an HPV-driven mouse model of skin cancer. We analyzed HPV-induced epithelial hyperplasia and squamous cell carcinoma formation, as well as growth of tumors inoculated into the dermis, in mice lacking skin mast cells. Unexpectedly, the absence of mast cells had no effect on HPV-induced epithelial growth or angiogenesis, on growth kinetics of inoculated tumors, or on the immunological tumor micro-milieu. Thus, the conspicuous recruitment of mast cells into tumor tissues cannot necessarily be equated with important mast cell functions in tumor growth. : Mast cells accumulate in high numbers in many human tumors, and they are widely viewed as important promoters of tumor growth. Ghouse et al. show that growth, angiogenesis, and the immunological micro-milieu of tumors growing in mice genetically deficient for mast cells are unchanged compared to control tumors. Keywords: mast cells, HPV-induced skin cancer, tumor angiogenesis, tumor micro-milieu

Tumor-mimicking primary angiitis of the central nervous system: initial and follow-up MR features

Energy Technology Data Exchange (ETDEWEB)

Lee, Youkyung; Kim, Ji-hoon; Kim, Eunhee; Yim, Yoo Jeong; Sohn, Chul-Ho [Department of Radiology, Seoul National University Hospital, Seoul (Korea); Park, Sung-Hye [Seoul National University, Department of Pathology, School of Medicine, Seoul (Korea); Chang, Kee-Hyun [Department of Radiology, Seoul National University Hospital, Seoul (Korea); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea); Seoul National University Medical Research Center, Neuroscience Research Institute, Seoul (Korea)

2009-10-15

Primary angiitis of the central nervous system (PACNS) is an extremely rare vasculitis of unknown etiology. The purpose of this study was to describe the initial and follow-up magnetic resonance (MR) imaging features of the tumor-mimicking PACNS. We retrospectively reviewed a total of 21 initial and follow-up brain MR images obtained in four patients with biopsy-proven PACNS mimicking brain tumor on MR images during the periods from 1 to 8.1 years. In the initial study, diffusion-weighted imaging (DWI; n=4), MR angiogram (n=4), conventional catheter angiogram (n=3), perfusion MR (n=1), and computed tomography (n=1) and proton MR spectroscopy (MRS; n=2) were included. The lesions of the brain were qualitatively assessed in terms of location, number, size, shape, signal intensity, absence or presence of hemorrhage, enhancement pattern, and changes on the follow-up studies. Initially, the lesion manifested as single suprasellar (n=1) and frontal hemispheric (n=1) mass and as multiple-enhancing lesions in the unilateral supratentorial hemisphere (n=2). A patient showed steno-occlusive lesions in the internal carotid and middle cerebral arteries. DWI, perfusion imaging, and MRS revealed inconsistent findings among the patients. On the follow-up studies, a patient had two relapses but there was either significant decrease in size and extent or disappearance of the lesions with immunosuppressive therapy in all patients. Tumor-mimicking PACNS shows variable features on initial MR images but shows good responses to appropriate immunosuppressive therapy on follow-up MR images. (orig.)

Tumor-mimicking primary angiitis of the central nervous system: initial and follow-up MR features

International Nuclear Information System (INIS)

Lee, Youkyung; Kim, Ji-hoon; Kim, Eunhee; Yim, Yoo Jeong; Sohn, Chul-Ho; Park, Sung-Hye; Chang, Kee-Hyun

2009-01-01

Primary angiitis of the central nervous system (PACNS) is an extremely rare vasculitis of unknown etiology. The purpose of this study was to describe the initial and follow-up magnetic resonance (MR) imaging features of the tumor-mimicking PACNS. We retrospectively reviewed a total of 21 initial and follow-up brain MR images obtained in four patients with biopsy-proven PACNS mimicking brain tumor on MR images during the periods from 1 to 8.1 years. In the initial study, diffusion-weighted imaging (DWI; n=4), MR angiogram (n=4), conventional catheter angiogram (n=3), perfusion MR (n=1), and computed tomography (n=1) and proton MR spectroscopy (MRS; n=2) were included. The lesions of the brain were qualitatively assessed in terms of location, number, size, shape, signal intensity, absence or presence of hemorrhage, enhancement pattern, and changes on the follow-up studies. Initially, the lesion manifested as single suprasellar (n=1) and frontal hemispheric (n=1) mass and as multiple-enhancing lesions in the unilateral supratentorial hemisphere (n=2). A patient showed steno-occlusive lesions in the internal carotid and middle cerebral arteries. DWI, perfusion imaging, and MRS revealed inconsistent findings among the patients. On the follow-up studies, a patient had two relapses but there was either significant decrease in size and extent or disappearance of the lesions with immunosuppressive therapy in all patients. Tumor-mimicking PACNS shows variable features on initial MR images but shows good responses to appropriate immunosuppressive therapy on follow-up MR images. (orig.)

Imaging of tumor viability in lung cancer. Initial results using 23Na-MRI

International Nuclear Information System (INIS)

Henzler, T.; Apfaltrer, P.; Haneder, S.; Schoenberg, S.O.; Fink, C.; Konstandin, S.; Schad, L.; Schmid-Bindert, G.; Manegold, C.; Wenz, F.

2012-01-01

23 Na-MRI has been proposed as a potential imaging biomarker for the assessment of tumor viability and the evaluation of therapy response but has not yet been evaluated in patients with lung cancer. We aimed to assess the feasibility of 23 Na-MRI in patients with lung cancer. Three patients with stage IV adenocarcinoma of the lung were examined on a clinical 3 Tesla MRI system (Magnetom TimTrio, Siemens Healthcare, Erlangen, Germany). Feasibility of 23 Na-MRI images was proven by comparison and fusion of 23 Na-MRI with 1 H-MR, CT and FDG-PET-CT images. 23 Na signal intensities (SI) of tumor and cerebrospinal fluid (CSF) of the spinal canal were measured and the SI ratio in tumor and CSF was calculated. One chemonaive patient was examined before and after the initiation of combination therapy (Carboplatin, Gemcitabin, Cetuximab). All 23 Na-MRI examinations were successfully completed and were of diagnostic quality. Fusion of 23 Na-MRI images with 1 H-MRI, CT and FDG-PET-CT was feasible in all patients and showed differences in solid and necrotic tumor areas. The mean tumor SI and the tumor/CSF SI ratio were 13.3 ± 1.8 x 103 and 0.83 ± 0.14, respectively. In necrotic tumors, as suggested by central non-FDG-avid areas, the mean tumor SI and the tumor/CSF ratio were 19.4 x 103 and 1.10, respectively. 23 Na-MRI is feasible in patients with lung cancer and could provide valuable functional molecular information regarding tumor viability, and potentially treatment response. (orig.)

Skin metastases from lung cancer: a case report.

Science.gov (United States)

Pajaziti, Laura; Hapçiu, Syzana Rexhepi; Dobruna, Shkendije; Hoxha, Naim; Kurshumliu, Fisnik; Pajaziti, Artina

2015-04-11

Lung cancer is one of the most frequent malignancies, with high mortality rates. It can metastasize in almost all organs, but more often invades hilar nodes, liver, adrenal glands, bones and brain. There are various data on the incidence of lung cancer metastases in the skin. In 1-12% of patients with lung cancer are developed skin metastases. Metastases in the skin may be the first sign of lung cancer. Forty-five years old Albanian male, smoker, was admitted to our department with multiple nodules localized in the skin of the head, neck, back and chest. The nodules measuring 5-15 millimeters in greatest dimension were round and skin-colored, with telangiectasias, firm and tender. They appeared in an eruptive form about two weeks before being admitted at our hospital. In addition, the patient exhibited signs of weight loss, anorexia and fatigue. Excisional biopsy was performed to one of the lesions. Histopathology confirmed metastatic nature of the lesion namely, malignant tumor of neuroendocrine phenotype consistent with small-cell carcinoma. Chest X-ray and computed tomography revealed an expansive process in the 7(th) segment of the left lung, left hilar and mediastinal lymphadenopathy and a suspicious initial secondary deposit in the left adrenal gland. The patient was referred to the department of oncology for further treatment. After the third cycle of chemotherapy, the magnetic resonance imaging revealed brain metastases. The patient passed away four months after the diagnosis of lung cancer first presented with skin metastases. Metastases in skin may be the first sign of lung cancer. Although rare appearing, we should raise suspicion in cases of atypical lesions in the skin not only of the smokers, but also of the non-smokers. Skin metastases from small-cell lung carcinoma are a poor prognostic indicator. The appearance of multiple skin metastases with other internal metastases shorten the survival time.

Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

International Nuclear Information System (INIS)

Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

2013-01-01

Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

International Nuclear Information System (INIS)

Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

2015-01-01

Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

Energy Technology Data Exchange (ETDEWEB)

Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

2015-08-14

Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

Moist skin care can diminish acute radiation-induced skin toxicity

International Nuclear Information System (INIS)

Momm, F.; Weissenberger, C.; Bertelt, S.; Henke, M.

2003-01-01

Background: Radiation treatment may induce acute skin reactions. There are several methods of managing them. Validity of these methods, however, is not sufficiently studied. We therefore investigated, whether moist skin care with 3% urea lotion will reduce acute radiation skin toxicity. Patients and Methods: 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent (mean total dose 60 Gy, range: 50-74 Gy) were evaluated weekly for acute skin reactions according to the RTOG-CTC score. In 63 patients, moist skin care with 3% urea lotion was performed. The control group consisted of 25 patients receiving conventional dry skin care. The incidence of grade I, II, and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test. The dose-time relations of individual skin reactions are described. Results: At some point of time during radiotherapy, all patients suffered from acute skin reactions grade I, > 90% from grade II reactions. 50% of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients (p = 0.03). Grade II reactions occurred at 51 Gy versus 34 Gy (p = 0.006). Further, 22% of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56% of the controls (p = 0.0007). Conclusion: Moist skin care with 3% urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors. (orig.)

Radiotherapy and skin tumors; Radiotherapie et tumeurs curanees

Energy Technology Data Exchange (ETDEWEB)

Calitchi, E.; KIrova, Y.; Le bourgeois, J.P. [Hopital Henri-Mondor, 94 - Creteil (France)

1998-09-01

Radiotherapy plays an important role in treatment of skin tumours. For skin carcinomas, external irradiation (kilo-voltage X-rays or electrons according to clinical characteristics) is more valuable than interstitial brachytherapy, which is recommended for tumours of the lip and of the nasal vestibule. In mycosis fungoides, total cutaneous electron beam radiation therapy is efficient for patients with limited superficial plaques. In the classical form of Kaposi`s sarcoma, radiotherapy can achieve local control-whereas it obtains good palliative results in the epidemic form. (author)

A case of radiation-induced skin cancer of the neck

International Nuclear Information System (INIS)

Matsushita, Tetsuya; Susuki, Takeo; Kikui, Tomoko; Masada, Yoshiko; Tahara, Shinya.

1994-01-01

The authors discuss the case of radiation-induced skin cancer of the neck in a 76-year-old woman who had undergone irradiation of tubercular lymphadenitis of the cervix while in her low teens. Some fifty years later, a squamous cell carcinoma developed in the irradiated region and in due course deeply invaded the sternocleidomastoidous muscle. Thus, a radical neck dissection was performed and the tumor and the lymph tissue removed en bloc, after which reconstruction was accomplished by using a latissimus dorsi musculocutaneous flap. With regard to the lessons learned from treating this case, three points are considered important and are listed below. When treating radiation-induced skin cancer patients, the head and neck regions should be examined in detail for the presence of other tumors. The excision of the skin surrounding the tumor should be as wide as possible, so as to remove skin that may have been also over-subjected to irradiation. The remaining skin surrounding the defect left by the excision is atrophic and thin. (author)

Ovarian tumor-initiating cells display a flexible metabolism

International Nuclear Information System (INIS)

Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

2014-01-01

An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L FFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

Ovarian tumor-initiating cells display a flexible metabolism

Energy Technology Data Exchange (ETDEWEB)

Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

2014-10-15

An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

Directory of Open Access Journals (Sweden)

Jesus Perez-Losada

Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

Penile Shaft : An Unusual Location For Skin Tags

Directory of Open Access Journals (Sweden)

Thami Gurvinder P

2003-01-01

Full Text Available Skin tags or acrochordons, commonly observed in the flexural surfaces and various folds of skin, are more frequently encountered in presence of obesity, diagetes and old age. Although lesions are quite characteristic clinically, at times these need to be differentiated from warts, fibromas and other benign tumors of skin and their appendages. A rare case with presence of skin tags over the shaft of penis is described.

Malignant Tumor Derived from Skin Melanocytes of a Bovine of Unusual Presentation: A Case Study

Directory of Open Access Journals (Sweden)

Carlos Alberto Chaves Velásquez

2015-05-01

Full Text Available Melanocytic tumors and melanomas in domestic animals include neoplasms composed of melanin-producing cells. In cattle, these tumors are rare and mostly benign, while malignant tumors are almost non-existent. The article reports the case of a female crossbred cow 38 months of age with a fluctuating mass located between the mandibular border and the left parotid region, about three months duration, with evident growth in the last thirty days. After surgical excision, a sample preserved in buffered formalin (10% was sent to the Laboratory of Pathology (University of Nariño—consisting of a fragment of 7.0 × 10.5 × 8.0 cm, ellipsoid, with skin and hair on one side, irregular surface, blackish brown, semi-soft consistency, and presence of shear translucent slimy content—for processing and inclusion in paraffin, cut to 5 μm thickness and stained with hematoxylin-eosin coloration. The forwarded tissue was classified as a neoplasm of malignant behavior derived from melanocytes, due to its cellular characteristics: growth pattern, pattern of distribution, severe cellular pleomorphism, anisocytosis, megalocytosis, nuclear pleomorphism, anisokaryosis, megalokaryosis, and involvement of blood vessel walls; additionally, the paraffin block was cut for immunohistochemical processing using monoclonal markers (S-100 DAKO® and Melan A DAKO®, contrasted with Mayer’s hematoxylin. Strong immunostaining of neoplastic cells is evident, and it constitutes the first reported case of this disease in Nariño (Colombia.

Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

Energy Technology Data Exchange (ETDEWEB)

Albert, R.E.; Burns, F.J.; Altshuler, B.

1978-02-01

The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.

Mid-infrared spectroscopy in skin cancer cell type identification

Science.gov (United States)

Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

2017-07-01

Mid infrared spectroscopy samples were developed for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin cancer diagnostics.

Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor.

Science.gov (United States)

Waldow, S M; Russell, G E; Wallner, P E

1992-01-01

Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment.

Skin Cancer (Including Melanoma)—Health Professional Version

Science.gov (United States)

Basal cell carcinoma and squamous cell carcinoma are referred to as nonmelanoma skin cancers. Melanoma is a malignant tumor of melanocytes, which make the melanin. Find evidence-based information on skin cancer treatment, causes and prevention, screening, research, genetics, and statistics.

Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

Science.gov (United States)

Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

2014-03-01

It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

Confocal microscopy patterns in nonmelanoma skin cancer and clinical applications.

Science.gov (United States)

González, S; Sánchez, V; González-Rodríguez, A; Parrado, C; Ullrich, M

2014-06-01

Reflectance confocal microscopy is currently the most promising noninvasive diagnostic tool for studying cutaneous structures between the stratum corneum and the superficial reticular dermis. This tool gives real-time images parallel to the skin surface; the microscopic resolution is similar to that of conventional histology. Numerous studies have identified the main confocal features of various inflammatory skin diseases and tumors, demonstrating the good correlation of these features with certain dermatoscopic patterns and histologic findings. Confocal patterns and diagnostic algorithms have been shown to have high sensitivity and specificity in melanoma and nonmelanoma skin cancer. Possible present and future applications of this noninvasive technology are wide ranging and reach beyond its use in noninvasive diagnosis. This tool can also be used, for example, to evaluate dynamic skin processes that occur after UV exposure or to assess tumor response to noninvasive treatments such as photodynamic therapy. We explain the characteristic confocal features found in the main nonmelanoma skin tumors and discuss possible applications for this novel diagnostic technique in routine dermatology practice. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

[Skin cancer as occupational disease].

Science.gov (United States)

Bauer, A

2016-11-01

The incidence of epithelial skin neoplasms, such as squamous cell carcinoma and basal cell carcinoma is significantly increasing worldwide. Leisure time solar UV exposure is causative in the overwhelming majority of cases in the general population; however, occupational exposure is responsible for a certain percentage of cases. Employees with a relevant exposure to polycyclic aromatic hydrocarbons in soot, raw paraffin, coal tar, anthracene, pitch or similar substances, to sunlight in outdoor occupations as well as to arsenic and ionizing radiation have a significantly increased risk to develop occupational skin cancer compared to the general population. In the official occupational disease list in the appendix of the German by-law on occupational diseases, the following occupational diseases concerning skin cancer are listed: BK 5102 "skin cancer and carcinoma in situ caused by soot, raw paraffin, coal tar, anthracene, pitch or similar substances" (e.g. various solid paraffins, asphalt and mazut as well as mineral oils, grease, cylinder and drilling oils), BK 5103 "squamous cell carcinoma or multiple actinic keratosis caused by natural UV radiation", BK 1108 "diseases caused by arsenic and its compounds" and BK 2402 "diseases caused by ionizing radiation". For further occupational exposure to carcinogenic substances and potential occupationally acquired skin tumors, no official lists are currently available. These cancers might be considered under a special opt out paragraph in the German Social Law (§ 9 para 2 SGB VII). Tumors in scars after occupational skin trauma or occupational burns are compensated as consequences of work accidents. The current official list of occupational skin cancers and new developments for expert opinions are described in this article.

MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

Energy Technology Data Exchange (ETDEWEB)

Yasuda, Kazuyo [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Kuroda, Takafumi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Takaya, Akari; Kubo, Terufumi; Kanaseki, Takayuki; Tsukahara, Tomohide [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hasegawa, Tadashi [Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Saito, Tsuyoshi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Sato, Noriyuki [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Torigoe, Toshihiko, E-mail: torigoe@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan)

2016-04-15

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

JWA deficiency suppresses dimethylbenz[a]anthracene-phorbol ester induced skin papillomas via inactivation of MAPK pathway in mice.

Directory of Open Access Journals (Sweden)

Zhenghua Gong

Full Text Available Our previous studies indicated that JWA plays an important role in DNA damage repair, cell migration, and regulation of MAPKs. In this study, we investigated the role of JWA in chemical carcinogenesis using conditional JWA knockout (JWA(Δ2/Δ2 mice and two-stage model of skin carcinogenesis. Our results indicated that JWA(Δ2/Δ2 mice were resistant to the development of skin papillomas initiated by 7, 12-dimethylbenz(aanthracene (DMBA followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA. In JWA(Δ2/Δ2 mice, the induction of papilloma was delayed, and the tumor number and size were reduced. In primary keratinocytes from JWA(Δ2/Δ2 mice, DMBA exposure induced more intensive DNA damage, while TPA-promoted cell proliferation was reduced. The further mechanistic studies showed that JWA deficiency blocked TPA-induced activation of MAPKs and its downstream transcription factor Elk1 both in vitro and in vivo. JWA(Δ2/Δ2 mice are resistance to tumorigenesis induced by DMBA/TPA probably through inhibition of transcription factor Elk1 via MAPKs. These results highlight the importance of JWA in skin homeostasis and in the process of skin tumor development.

Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans

Czech Academy of Sciences Publication Activity Database

Stapelberg, M.; Zobalová, Renata; Nguyen, M.N.; Walker, T.; Stantic, M.; Goodwin, J.; Pasdar, E.A.; Thai, T.; Prokopová, Kateřina; Yan, B.; Hall, S.; de Pennington, N.; Thomas, S.R.; Grant, G.; Štursa, Jan; Bajziková, Martina; Meedeniya, A.C.B.; Truksa, Jaroslav; Ralph, S. J.; Ansorge, O.; Dong, L.-F.; Neužil, Jiří

2014-01-01

Roč. 67, FEB (2014), s. 41-50 ISSN 0891-5849 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP305/12/1708 Institutional support: RVO:86652036 ; RVO:61388963 Keywords : IDO * Tumor-initiating cells * Mitocans * Mitochondrially targeted vitamin E succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.736, year: 2014

Photocarcinogenesis and Skin Cancer Prevention Strategies.

Science.gov (United States)

Seebode, Christina; Lehmann, Janin; Emmert, Steffen

2016-03-01

In this review the basic principles of UV-induced carcinogenesis are summarized and the state of the art diagnosis and therapeutic strategies are discussed. The prevalent keratinocyte-derived neoplasms of the skin are basal cell and squamous cell carcinomas. Cutaneous melanoma is less frequent but associated with high mortality. Common risk factors for all three tumor entities include sun exposure and DNA-repair deficiencies. Photocarcinogenesis follows a multistep model of cancer development in which ultraviolet-induced DNA damage leads to mutations resulting in activation of oncogenes or silencing of tumor-suppressor genes. This ends in a cellular mutator phenotype even more prone to mutation acquisition. DNA repair, especially the nucleotide excision repair (NER) pathway, counteracts mutation formation and skin cancer development. This is vividly demonstrated by the NER-defective disorder xeroderma pigmentosum. Primary skin cancer preventative strategies, therefore, include reduction of DNA photodamage by protection from the sun. Secondary preventative strategies include skin cancer screening. This implies standard examination techniques with the naked eye, an epiluminescence microscope, or digital epiluminescence microscopy. More advanced techniques include confocal laser scan microscopy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Skin carcinomas: radiobiological principles, radiotherapeutic techniques and clinical management

International Nuclear Information System (INIS)

Schmidt-Ullrich, Rupert K. A.; Johnson, Christopher R.

1995-01-01

Purpose/Objective: The course will be divided into three major topics: (1) Review of radiobiological principles as they apply to the radiotherapeutic management of skin carcinomas; (2) review of radiotherapeutic techniques including beam qualities, beam collimation, tissue dose profiles, and the relative indications of external beam irradiation vs. brachytherapy; (3) comprehensive review of the tumor biology of skin malignancies, including malignant melanoma, and of the relative indications for radiotherapeutic and/or surgical management. (1) Review of critical data which have lead to currently applied principles of time-dose-volume concepts in the radiotherapeutic management of skin carcinomas. Emphasis will be placed on the relative importance of fraction size and overall treatment time on tumor control probability and acute and late normal tissue toxicity. (2) Considering that radiotherapy in the management of skin carcinomas is often used to minimize patient disfiguration and to preserve critical body functions (e.g. eye lids) the technical aspects of radiotherapy delivery are most critical. Careful evaluation of the extent of the lesions including evaluation of their depth of invasion will determine the quality of the radiation beams, orthovoltage and low energy electrons being the most useful. Beam harding for orthovoltage beams and secondary and tertiary (skin) collimation of appropriate electron beams are critical. For more extensive and deeply invasive lesions contour-shaping through customized bolus material is essential. Equally important is the familiarity with custom shielding of critical structures, such as eyes, ears, oral cavity and central nervous system structures. Brachytherapy applications in the treatment of skin carcinomas is limited but should be considered when implants with high dose uniformity can be constructed. (3) The discussion of clinical management will start with a discussion of tumor biological properties of the diverse malignant

Radiotherapy for Merkel cell carcinoma of the skin

International Nuclear Information System (INIS)

Nathu, Rakesh M.; Mendenhall, William M.; Parsons, James T.

1997-01-01

Purpose/Objective: Merkel cell carcinoma is a rare, aggressive neuroendocrine tumor of the skin with a predisposition for local-regional and distant spread. The addition of radiotherapy after wide local excision has improved local control, but distant spread continues to be a significant problem. This is an update of our experience in the treatment of Merkel cell carcinoma at the University of Florida. Materials and Methods: Of 25 patients treated for Merkel cell carcinoma at the University of Florida between 1984 and 1996, minimum follow-up was 1 year; no patient was lost to follow-up. Nineteen patients were treated at the time of the initial diagnosis, and six were treated after local-regional recurrence. Of the 19 previously untreated patients, 14 had primary sites in the head and neck region, and five had primary sites elsewhere. Results: The 5-year absolute survival, cause-specific survival, and local-regional control rates for the entire group were 26%, 30%, and 79%, respectively. Patients treated with radiotherapy at the time of initial presentation had 5-year absolute survival, cause-specific survival, and local-regional control rates of 36%, 42%, and 74%, respectively. Most deaths were due to distant metastasis. Site of the primary tumor (in or out of the head and neck region) was not associated with any difference in the outcome. Of six patients treated at the time of local-regional recurrence, five died of distant metastasis at 8, 16, 27, 37, and 38 months from the time of treatment. One patient was alive and without evidence of disease 24 months after treatment. All patients treated at the time of local-regional recurrence had local-regional control after radiotherapy. Conclusion: This update confirms that radiotherapy and wide local excision is effective local-regional treatment for Merkel cell carcinoma of the skin, but distant metastasis remains a significant problem in this disease. The role and effectiveness of chemotherapy as part of the initial

Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

International Nuclear Information System (INIS)

Tong, Ying; Smith, M.A.; Tucker, S.B.

1997-01-01

Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

Neurotrophin Signaling via TrkB and TrkC Receptors Promotes the Growth of Brain Tumor-initiating Cells*

Science.gov (United States)

Lawn, Samuel; Krishna, Niveditha; Pisklakova, Alexandra; Qu, Xiaotao; Fenstermacher, David A.; Fournier, Michelle; Vrionis, Frank D.; Tran, Nam; Chan, Jennifer A.; Kenchappa, Rajappa S.; Forsyth, Peter A.

2015-01-01

Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma. PMID:25538243

Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells.

Science.gov (United States)

Lawn, Samuel; Krishna, Niveditha; Pisklakova, Alexandra; Qu, Xiaotao; Fenstermacher, David A; Fournier, Michelle; Vrionis, Frank D; Tran, Nam; Chan, Jennifer A; Kenchappa, Rajappa S; Forsyth, Peter A

2015-02-06

Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Anti-tumor activity of Aloe vera against DMBA/croton oil-induced skin papillomagenesis in Swiss albino mice.

Science.gov (United States)

Saini, M; Goyal, Pradeep Kumar; Chaudhary, Geeta

2010-01-01

Human populations are increasingly exposed to various carcinogens such as chemicals, radiation, and viruses in the environment. Chemopreventive drugs of plant origin are a promising strategy for cancer control because they are generally nontoxic or less toxic than synthetic che-mopreventive agents, and can be effective at different stages of carcinogenesis. The present investigation was undertaken to explore the antitumor activity of topical treatment with aloe vera (Aloe vera) gel, oral treatment with aloe vera extract, and topical and oral treatment with both gel and extract in stage-2 skin carcinogenesis in Swiss albino mice induced by 7,12-dim ethylbenz(a)anthracene (DMBA) and promoted croton (Croton tiglium) oil. The animals were randomly divided into 4 groups and treated as follows: Group I, DMBA + croton oil only (controls); Group II, DMBA + croton oil + topical aloe vera gel; Group III, DMBA + croton oil + oral aloe vera extract; Group I V, DMBA + croton oil + topical aloe vera gel + oral aloe vera extract. Results showed that body weight was significantly increased from 78.6% in the control group (Group I) to 92.5%, 87.5%, and 90.0% in Groups II, III, and I V, respectively. A 100% incidence of tumor development was noted in Group I, which was decreased to 50%, 60%, and 40% in Groups II, III, and I V, respectively. Also in Groups II, III, and IV, the cumulative number of papillomas was reduced significantly from 36 to 12, 15, and 11; tumor yield from 3.6 to 1.2, 1.5, and 1.1; and tumor burden from 3.6 to 2.4, 2.50, and 2.75, respectively, after treatment with aloe vera. Conversely, the average latent period increased significantly from 4.9 (Group I) to 5.23, 5.0, and 6.01 weeks in Groups II, III, and I V, respectively. We conclude that aloe vera protects mice against DMBA/croton oil-induced skin papillomagenesis, likely due to the chemopreventive activity of high concentrations of antioxidants such as vitamins A, C, and E; glutathione peroxidase; several

Recommendations for standardized diagnostics, treatment and following care in tumor diseases. Geriatric patient with tumor disease

International Nuclear Information System (INIS)

Hagmueller, E.; Neises, M.; Queisser, W.; Richter, H.; Schneider, G.

2001-01-01

The recommendations for the treatment of geriatric patients with tumor disease, presented in the paper, cover: surgery; chemotherapy; radiotherapy and immunotherapy. Radiotherapy is recommended for skin tumors, pain treatment in the bone metastases (40 - 50 Gy), system diseases (with reduction of the usual size of the irradiated area), small size tumors etc. It is considered as an appropriate method (excluding wide fields) for geriatric outpatients

Radiation-induced skin cancer and radiodermatitis of the head and neck

International Nuclear Information System (INIS)

van Vloten, W.A.; Hermans, J.; van Daal, W.A.

1987-01-01

From a cohort of 2400 patients who had been irradiated 19 to 48 years previously for benign diseases in the head and neck region a randomly selected group of 605 patients was selected and traced back. From the 360 patients alive, 257 were examined clinically and 49 were examined by questionnaire for radiation-induced skin tumors and radiodermatitis. In 21 patients, a total of 30 skin tumors were diagnosed. In 8 of 21 patients, 10 skin carcinomas were detected at recall. A dose-effect relationship of 40 carcinomas/10(4) persons/Gy for a median follow-up period of 41 years for the area exposed was calculated. The severity of radiodermatitis is associated with a higher prevalence of skin cancer. The number of radiation-induced skin cancers rises with the post-treatment time. Because of these late radiation effects, radiotherapy of benign skin lesions is contraindicated, especially now that other therapy modalities are available

Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse

Energy Technology Data Exchange (ETDEWEB)

Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Bunde, Kristi L. [College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Harper, Tod A. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); McQuistan, Tammie J. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Löhr, Christiane V. [Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Bramer, Lisa M. [Applied Statistics and Computational Modeling, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Waters, Katrina M. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Tilton, Susan C. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Krueger, Sharon K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); and others

2015-09-01

FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8 h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8 h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4 h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8 h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. - Highlights: • Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE. • Cyp1b1 expression impacts expression of other PAH metabolizing enzymes. • cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver • Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.

An Algorithmic Approach for the Reconstruction of Nasal Skin Defects: Retrospective Analysis of 130 Cases

Directory of Open Access Journals (Sweden)

Berrak Akşam

2016-06-01

Full Text Available Objective: Most of the malignant cutaneous carcinomas are seen in the nasal region. Reconstruction of nasal defects is challenging because of the unique anatomic properties and complex structure of this region. In this study, we present our algorithm for the nasal skin defects that occurred after malignant skin tumor excisions. Material and Methods: Patients whose nasal skin was reconstructed after malignant skin tumor excision were included in the study. These patients were evaluated by their age, gender, comorbities, tumor location, tumor size, reconstruction type, histopathological diagnosis, and tumor recurrence. Results: A total of 130 patients (70 female, 60 male were evaluated. The average age of the patients was 67.8 years. Tumors were located mostly at the dorsum, alar region, and tip of the nose. When reconstruction methods were evaluated, primary closure was preferred in 14.6% patients, full thickness skin grafts were used in 25.3% patients, and reconstruction with flaps were the choice in 60% patients. Different flaps were used according to the subunits. Mostly, dorsal nasal flaps, bilobed flaps, nasolabial flaps, and forehead flaps were used. Conclusion: The defect-only reconstruction principle was accepted in this study. Previously described subunits, such as the dorsum, tip, alar region, lateral wall, columella, and soft triangles, of the nose were further divided into subregions by their anatomical relations. An algorithm was planned with these sub regions. In nasal skin reconstruction, this algorithm helps in selection the methods for the best results and minimize the complications.

Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice – Lessons for tumor immunity

International Nuclear Information System (INIS)

Wagner, Alexander Y; Holle, Eric; Holle, Lori; Yu, Xianzhong; Schwamberger, Günter

2008-01-01

Rejection of transplanted tumors by the immune system is a rare event in syngeneic hosts, and is considered to be dependent on the local interaction of defensive immune reactions and tumor tolerance mechanisms. Here, we have enlisted the aid of a unique set of embryo-aggregated lineage chimeric mice derived from C57/BL6 and FVB donors to study the interplay between local and systemic tumor immunity and tolerance in rejection of mouse B16 melanoma cells, syngeneic to the C57/BL6 donor strain. Two variants of embryo-aggregated chimeric mice with either variable or no contribution of C57-derived cells to their skin were generated by the fusion of different ratios of morula stage blastomers. Chimeric mice were analyzed for s.c. growth of B16 tumors in comparison to their respective donor strains as well as normal F1 hybrids, and the relative frequencies of cellular components of the immune system by FACS analysis of peripheral blood or lymph node cells. B16 tumors grew significantly faster in mice with full chimerism in their skin as compared to syngeneic C57 or semi-syngeneic C57 × FVB F1 hosts. In contrast, s.c. tumor growth was either absent or significantly reduced in chimeric mice lacking C57-derived cells in their skin, but tolerant to C57 tissue in other organs. Comparison of the relative frequencies of various immune cells in the periphery via FACS-analysis did not reveal any significant differences between the two types of chimeric mice with respect to their donor strains. Our data suggest a complex interplay between mechanisms of local peripheral tolerance and innate antitumor mechanisms possibly involving NK cell allorecognition as a basis for the differential growth or rejection of B16 tumors in these unique chimeric mice, which we suggest to constitute a valuable new model system for the study of immune-mediated tumor rejection

Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice – Lessons for tumor immunity

Directory of Open Access Journals (Sweden)

Yu Xianzhong

2008-12-01

Full Text Available Abstract Background Rejection of transplanted tumors by the immune system is a rare event in syngeneic hosts, and is considered to be dependent on the local interaction of defensive immune reactions and tumor tolerance mechanisms. Here, we have enlisted the aid of a unique set of embryo-aggregated lineage chimeric mice derived from C57/BL6 and FVB donors to study the interplay between local and systemic tumor immunity and tolerance in rejection of mouse B16 melanoma cells, syngeneic to the C57/BL6 donor strain. Methods Two variants of embryo-aggregated chimeric mice with either variable or no contribution of C57-derived cells to their skin were generated by the fusion of different ratios of morula stage blastomers. Chimeric mice were analyzed for s.c. growth of B16 tumors in comparison to their respective donor strains as well as normal F1 hybrids, and the relative frequencies of cellular components of the immune system by FACS analysis of peripheral blood or lymph node cells. Results B16 tumors grew significantly faster in mice with full chimerism in their skin as compared to syngeneic C57 or semi-syngeneic C57 × FVB F1 hosts. In contrast, s.c. tumor growth was either absent or significantly reduced in chimeric mice lacking C57-derived cells in their skin, but tolerant to C57 tissue in other organs. Comparison of the relative frequencies of various immune cells in the periphery via FACS-analysis did not reveal any significant differences between the two types of chimeric mice with respect to their donor strains. Conclusion Our data suggest a complex interplay between mechanisms of local peripheral tolerance and innate antitumor mechanisms possibly involving NK cell allorecognition as a basis for the differential growth or rejection of B16 tumors in these unique chimeric mice, which we suggest to constitute a valuable new model system for the study of immune-mediated tumor rejection.

Papillary endothelial hyperplasia (Masson's tumor) in children.

Science.gov (United States)

Liné, A; Sanchez, J; Jayyosi, L; Birembaut, P; Ohl, X; Poli-Mérol, M-L; François, C

2017-06-01

The intravascular papillary endothelial hyperplasia (IPEH/Masson's tumor) is a rare benign tumor of the skin and subcutaneous vessels. We report, in four pediatric cases, clinical presentation, care (diagnostic and surgical) of Masson's tumor in children. Two boys (two years) and two girls (four and six years) showed a pain subcutaneous tumor (one to five centimeters). They were in the transverse abdominal muscle, between two metatarsals, at the front of thigh and in the axilla. Imaging performed (MRI, Doppler ultrasound) evoked either a hematoma, a lymphangioma or hemangioma. The indication for removal was selected from pain and/or parental concern. The diagnosis was histologically. A lesion persisted in residual form (incomplete initial resection), and is currently not scalable for eleven years. This tumor is characterized by excessive proliferation and papillary endothelial cells in the vessels, following a thrombotic event. It is found mainly in adults (no specific age), and preferentially localizes in the face and limbs. The clinical differential diagnosis of this tumor is angiosarcoma. The imagery has not allowed in our series to diagnose but still essential to eliminate differential diagnoses. Only surgical excision with histological examination can differentiate. Our study emphasizes the possibility of pediatric cases with two cases of unusual locations (abdominal and axilla). Clinical presentations we met, now lead us to direct our histologist looking for a Masson tumor in any child with a subcutaneous tumor and/or intramuscular pain, sudden onset, and vascular appearance (after excluding an arteriovenous malformation). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Osteotoxicity after chronic dietary administration of 13-CIS-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion

International Nuclear Information System (INIS)

Forsyth, K.S.; Gensler, H.L.; Watson, R.R.

1989-01-01

In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-O-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU or retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP/g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion results in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased O-fold, 1.4-fold, and 3.6-fold. Bone deformities was augmented O-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium did not alter the bone toxicity of RP. 13-cis-retionic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidence by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osterotoxicities were similar in the mice fed diets supplemented with RP and CRA

Applicability of the {sup 9}Be(d,n){sup 10}B reaction to AB-BNCT skin and deep tumor treatment

Energy Technology Data Exchange (ETDEWEB)

Capoulat, M.E., E-mail: capoulat@tandar.cnea.gov.ar [Gerencia de Investigacion y Aplicaciones, CNEA. Av. Gral. Paz 1499 (B1650KNA), San Martin, Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin, M. de Irigoyen 3100 (1650), San Martin, Buenos Aires (Argentina)] [CONICET, Avenida Rivadavia 1917 (C1033AAJ), Buenos Aires (Argentina); Minsky, D.M.; Kreiner, A.J. [Gerencia de Investigacion y Aplicaciones, CNEA. Av. Gral. Paz 1499 (B1650KNA), San Martin, Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin, M. de Irigoyen 3100 (1650), San Martin, Buenos Aires (Argentina)] [CONICET, Avenida Rivadavia 1917 (C1033AAJ), Buenos Aires (Argentina)

2011-12-15

In the range of low bombarding energies (less than about 1.5 MeV) the {sup 9}Be(d,n){sup 10}B reaction produces neutron spectra that can be moderated depending on the choice of the target thickness and the deuteron bombarding energy. In this work, a Monte Carlo simulation study to determine the capability of this reaction to deliver enough dose to efficiently control both skin and deep seated tumors has been performed by means of MCNP calculations using eight optimized {sup 9}Be targets.

Radiation Therapy in Elderly Skin Cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Hee [Keimyung University College of Medicine, Daegu (Korea, Republic of)

2008-06-15

To evaluate the long term results (local control, survival, failure, and complications) after radiation therapy for skin cancer in elderly patients. The study spanned from January 1990 to October 2002. Fifteen elderly patients with skin cancer were treated by radiotherapy at the Keimyung University Dongsan Medical Center. The age distribution of the patients surveyed was 72 to 95 years, with a median age of 78.8 years. The pathologic classification of the 15 patients included squamous cell carcinoma (10 patients), basal cell carcinoma (3 patients), verrucous carcinoma (1 patient) and skin adnexal origin carcinoma (1 patient). The most common tumor location was the head (13 patients). The mean tumor diameter was 4.9 cm (range 2 to 9 cm). The radiation dose was delivered via an electron beam of 6 to 15 MeV. The dose range was adjusted to the tumor diameter and depth of tumor invasion. The total radiation dose ranged from 50{approx}80 Gy (mean: 66 Gy) with a 2 Gy fractional dose prescribed to the 80% isodose line once a day and 5 times a week. One patient with lymph node metastasis was treated with six MV photon beams boosted with electron beams. The length of the follow-up periods ranged from 10 to 120 months with a median follow-up period of 48 months. The local control rates were 100% (15/15). In addition, the five year disease free survival rate (5YDFS) was 80% and twelve patients (80%) had no recurrence and skin cancer recurrence occurred in 3 patients (20%). Three patients have lived an average of 90 months (68{approx}120 months) without recurrence or metastasis. A total of 9 patients who died as a result of other causes had a mean survival time of 55.8 months after radiation therapy. No severe acute or chronic complications were observed after radiation therapy. Only minor complications including radiation dermatitis was treated with supportive care. The results suggest that radiation therapy is an effective and safe treatment method for the treatment of skin

Breast disease with skin thickening: differential diagnosis with mammography and ultrasonography

Energy Technology Data Exchange (ETDEWEB)

Shin, Young Rok; Kim, Hak Hee; Cha, Eun Suk; Park, Hye Seong; Kim, Ki Tae; Shinn, Kyung Sub [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

1999-02-01

Diffuse skin thickening of the breast is produced by lymphedema usually secondary to obstruction of the axillary lymphatics. On physical examination, the affected breast is, due to increased fluid content, larger, heavier, and of higher overall density. Mammography reveals an increased coarse reticular pattern. Thickening of the skin can have many causes. It may be a result of tumor invasion or a tumor in the dermal lymphatics ; or because of lymphatic congestion through obstruction of lymphatic drainage within the breast, in the axilla, or centrally in the mediastinum. Further causes may be congestive heart failure, benign inflammation, primary skin processes such as psoriasis, or systemic diseases which involve the skin. Mammographic appearance is known to be nonspecific. Ultrasound can demonstrate skin thickening directly, but despite some reports suggesting that the cause of skin thickening can be inferred from the results of ultrasound, this is not usually of practical importance. The purpose of this study is to review the causes of skin thickening of the breast and to use mammography and US to differentiate the causes.

Skin carcinogenesis in man and in experimental models

International Nuclear Information System (INIS)

Hecker, E.; Jung, E.G.; Marks, F.; Tilgen, W.

1993-01-01

This book presents an updated overview of the current state of the art in scientific, experimental and clinical investigations on the generation and the prevention of cancer of the skin. From the achievements presented, marked refinements in the assessment of the risk of cancer, by environmental and endogenous factors, including tumor virus, will be stimulated. They include the problem of the stratospheric 'ozone holes' above both poles of the earth causing much public concern as expressed by current headlines in the media and by the United Nations Environmental Program. Moreover, new ideas will merge for developing specific approaches to explore the mechanistic, i.e. ultimately the molecular-biological, causes of skin cancer and others. In addition, the experimental utilization of oncogens and of other techniques of molecular biology at all levels of the biology of tissues and cells, may open up entirely new facets in the research on skin cancer. Detailed knowledge of the mechanistic aspects of skin carcinogenesis may give important hints with respect to 'tailor-make' and utilize new anti-tumor agents in the therapy of skin cancer for the benefit of the cancer patient. (orig.). 67 figs., 44 tabs

Radiation-induced cancer of the skin in man

International Nuclear Information System (INIS)

Kiyono, Kunihiro; Moriya, Kumiko; Kobayashi, Toshio

1981-01-01

Eight cases of radiation induced cancer of the skin observed at the Shinshu University during 30 years from 1951 to 1938 were reported. All of the tumors were squamous cell carcinomas; 7 out of 8 cases occurred in males. Primary conditions for which irradiation was given were 6 cases of benign disorders of various skin disease and 2 cases of spinal tuberculosis. The mean age at which these patients were first subjected to radiation therapy was 31 years. At the time when the diagnosis of skin cancer was established, the mean age was 47 years, with a range from 35 to 58 years. The latent period distributed between 9 and 28 years, with the average of 16.4 years. The estimated radiation doses sufficient to induce cancer of the skin was found to be some thousands R or more, the lowest irradiation dose being about 2,000 R. There was no close correlation between the radiation dose and the latent period, nor between the age of the patient at the time of irradiation and the latent period. The tumors usually occurred in the skin areas where extensive irradiation changes were shown, especially in ulcerative area. (author)

Ability of spleen cells from tumor bearing mice to transfer immunologic memory

Energy Technology Data Exchange (ETDEWEB)

Plavsic, B.; Jurin, M. (Zagreb Univ. (Yugoslavia)); Ugarkovic, B. (Institut Rudjer Boskovic, Zagreb (Yugoslavia))

1983-01-01

The ability of splenocytes from tumorous mice to transfer immunologic memory was tested. Three syngeneic experimental tumors from highly inbred strains were used; fibrosarcoma, lymphoma and Lewis lung carcinoma. Splenocytes from tumorous mice were collected after rejection of allogeneic skin which had been grafted at different stages of the tumor disease, and injected into lethally irradiated syngeneic recipients. These secondary hosts were grafted with the same allogeneic skin graft as their donors and the ability of cells transplanted from tumorous donors to transfer memory to allograft was tested. Tumorous mice seemed to have more memory cells (T lymphocytes) in their spleens than the controls.

Evaluation of the Photoprotective Effect of Dongchongxiacao (Paecilomyces japonica) Extract against Ultraviolet Radiation-induced Skin Wrinkling and Cancer

International Nuclear Information System (INIS)

Lee, Hae June; Moon, Chang Jong; Kim, Jong Choon; Kim Sung Ho; Jung, Uhee; Jo, Sung Kee; Jang, Jong Sik

2012-01-01

To evaluate the ability of Dongchongxiacao (Paecilomyces japonica ) extract (PJE) to protect the skin from photo damage, the gross and microscopic changes in the skin of hairless mice and PJE-treated mice exposed chronically to ultraviolet (UV) were examined. The skin of the UV-irradiated mice showed characteristic signs of photo aging, such as deep wrinkles across the back. PJE-treated mice showed a significantly decreased wrinkling score. By the 22nd week, 88.9% (i.p. with saline) or 44.4% (topical administration with cream base) of the UV-irradiated mice developed at least one tumor. PJE delayed tumor onset significantly. PJE (i.p.) was also effective in reducing the occurrence of UV radiation-induced skin tumors and reduced the number of tumors per mouse. After 22 weeks of treatment, 80.0% (i.p.) and 75.0% (topical) of the mice treated with PJE were tumor-free. Tumor multiplicity was reduced by 96.2% (i.p.) in the PJE treated groups. It is noted that skin that is chronically exposed to UV is subject to photo aging and photo carcinogenesis and regular use of PJE would prevent these photo damaging effects of UV.

Studies into the transplantation biology of ultraviolet light-induced tumors

International Nuclear Information System (INIS)

Daynes, R.A.; Spellman, C.W.; Woodward, J.G.; Stewart, D.A.

1977-01-01

The majority of skin tumors induced in mice by ultraviolet (uv) light are rejected when implanted into normal syngeneic recipients. Subcarcinogenic levels of uv light exposure render the normally resistant mice susceptible to tumor challenge. The immunoregulatory effect of uv light appears to be additive, since the growth rate of a tumor transplant is dependent upon the length of uv exposure administered prior to implantation. This suppressive influence does not appear to be directly mediated by the uv light, because the amputation of uv-irradiated tail skin allows for a retention of tumor resistance in otherwise tumor-susceptible hosts. uv-irradiated mice could also be immunized against uv tumors, which suggests that immune recognition of tumor-specific transplantation antigens has not been inhibited. The ability of uv exposure to alter normal immunological reactivity to uv-induced tumors is possibly an integral factor in the mechanism underlying uv carcinogenesis

A Comparison of the Local Flap and Skin Graft by Location of Face in Reconstruction after Resection of Facial Skin Cancer.

Science.gov (United States)

Lee, Kyung Suk; Kim, Jun Oh; Kim, Nam Gyun; Lee, Yoon Jung; Park, Young Ji; Kim, Jun Sik

2017-12-01

Surgery for reconstruction of defects after surgery should be performed selectively and the many points must be considered. The authors conducted this study to compare the local flap and skin graft by facial location in the reconstruction after resection of facial skin cancer. The authors performed the study in patients that had received treatment in Department of Plastic Surgery, Gyeongsang National University. The cases were analyzed according to the reconstruction methods for the defects after surgery, sex, age, tumor site, and tumor size. Additionally, the authors compared differences of aesthetic satisfaction (out of 5 points) of patients in the local flap and skin graft by facial location after resection of facial skin cancer by dividing the face into eight areas. A total of 153 cases were confirmed. The most common facial skin cancer was basal cell carcinoma (56.8%, 87 cases), followed by squamous cell carcinoma (37.2%, 57 cases) and bowen's disease (5.8%, 9 cases). The most common reconstruction method was local flap 119 cases (77.7%), followed by skin graft 34 cases (22.3%). 86 patients answered the questionnaire and mean satisfaction of the local flap and skin graft were 4.3 and 3.5 ( p =0.04), respectively, indicating that satisfaction of local flap was significantly high. When comparing satisfaction of patients according to results, local flap shows excellent effects in functional and cosmetic aspects would be able to provide excellent results rather than using a skin graft with poor touch and tone compared to the surrounding normal skin.

Functional restoration of penis with partial defect by scrotal skin flap.

Science.gov (United States)

Zhao, Yue-Qiang; Zhang, Jie; Yu, Mo-Sheng; Long, Dao-Chou

2009-11-01

We investigated a reconstructive method with better sensory and erectile function for partial penile defects and report our long-term results of surgical correction using scrotal skin flaps. We retrospectively analyzed the records of 18 patients with penile defects referred to us between 1992 and 2007. All cases were treated with a scrotal skin flap initially to repair the secondary defect after penile elongation. Of the 18 cases treated during the 15-year period the mechanism of primary injury was circumcision in 3, animal bite in 9 and penile tumor dissection in 6. Penile elongation, division of the suspensory ligament and scrotal skin flaps achieved penile augmentation and enhancement. Six cases were treated with a bilateral scrotal skin flap supplied by the anterior scrotal artery and 12 were repaired with a total anterior scrotal skin flap supplied by the anterior and posterior scrotal arteries. Penile length in the flaccid and erectile states was obviously increased postoperatively (p <0.05). All patients were followed 1 to 9 years (mean 2.3) postoperatively. Deep and superficial sensation recovered and erectile function was retained. Of the 18 patients 15 reported satisfied sexual intercourse during the 0.5 to 5-year followup. The method of correcting partial penile defect using scrotal skin flaps is effective and simple according to our long-term experience. This method achieves reasonable cosmesis and penile length in most cases with better sensory and erectile function.

A case of likely radiation-induced synchronous esophageal and skin carcinoma following post-operative radiation for breast cancer

International Nuclear Information System (INIS)

Kanogawa, Naoya; Shimada, Hideaki; Kainuma, Osamu; Cho, Akihiro; Yamamoto, Hiroshi; Itami, Makiko; Nagata, Matsuo

2009-01-01

A 71-year-old woman was admitted in January 2008 with on upper thoracic esophageal squamous cell carcinoma and a right chest wall skin tumor. When she was 32 years old, she had a radical mastectomy for right breast cancer and received postoperative radiation. Due to the presence of lung adhesions, trans-thoracic esophagectomy could not be done; thus, a blunt dissection was performed. She was discharged on the 19 th postoperative day. On pathology, a pT2N0M0 (pStage II) esophageal tumor was diagnosed. A resection of her skin tumor underwent 79 days after the esophageal surgery; on pathology, the skin tumor was diagnosed as a basal cell carcinoma. Since the esophageal tumor and the skin tumor occurred in the same area that had received radiation therapy, these tumors were diagnosed as being radiation-induced secondary tumors. In the English language medical literature, several reports of radiation-induced esophageal cancer occurring as a second cancer after radiotherapy for breast cancer have been published. Radiation-induced esophageal cancer rates may increase in Japan given the number of women who previously received radiotherapy for breast cancer. (author)

SMART SKINS - A Development Roadmap

Science.gov (United States)

Lochocki, Joseph M.

1990-02-01

The Air Force Project Forecast II identified a number of key technology initiatives for development. This paper addresses one such initiative, PT-16, Smart Skins. The concept of the Smart Skin is introduced by briefly highlighting its attributes and potential advantages over standard avionics packaging and maintenance, and then goes on to describe some of the key ingredients necessary for its development. Problem areas are brought out along with some of the required trades that must be made. Finally, a time phased development roadmap is introduced which shows Calspan's proposed sequence of technology development programs that can, in combination, lead to first functional Smart Skins implementations in narrowband form in the late 1990's and in wideband form in first decade of the twenty - first century. A Smart Skins implementation in integral aircraft skin structure form will take at least until 2010.

Core outcome sets in dermatology: report from the second meeting of the International Cochrane Skin Group Core Outcome Set Initiative.

Science.gov (United States)

Kottner, J; Jacobi, L; Hahnel, E; Alam, M; Balzer, K; Beeckman, D; Busard, C; Chalmers, J; Deckert, S; Eleftheriadou, V; Furlan, K; Horbach, S E R; Kirkham, J; Nast, A; Spuls, P; Thiboutot, D; Thorlacius, L; Weller, K; Williams, H C; Schmitt, J

2018-04-01

Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG-COUSIN) supports the development of core outcomes in dermatology. In the second CSG-COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers. © 2018 British Association of Dermatologists.

Laser-induced fluorescence for the detection of esophageal and skin cancer

Science.gov (United States)

Vo-Dinh, Tuan; Panjehpour, Masoud; Overholt, Bergein F.; Julius, Clark E.; Overholt, Suzanne; Phan, Mary N.

2003-07-01

Laser-induced fluorescence (LIF) is used for in-vivo cancer diagnosis of the esophagus and skin cancer. For esophageal measurements a fiberoptic probe inserted through an endoscope was used. Autofluorescence of normal and malignant tissues were measured directly on patient skin without requiring an endoscope. Measurement of the fluorescence signal from the tissue was performed using laser excitation at 410 nm. The methodology was applied to differentiate normal and malignant tumors of the esophagus and malignant skin lesions. The results of this LIF approach were compared with histopathology results of the biopsy samples and indicated excellent agreement in the classification of normal and malignant tumors for the samples investigated.

A case of basal cell epitheliomas developed on chronic radiodermatitis (so-called roentgen-skin)

International Nuclear Information System (INIS)

Kuroda, Takaya; Yasuhara, Minoru

1980-01-01

A woman 63 years old had received an unknown amount of roentgen rediation from a physician for spondylitis tuberculosa of the thoracic vertebrae fifty years ago. About five years ago two small brownish black tumors appeared on her back and gradually increased. Within the past month ulcer and bleeding in these tumors. The Patient presented a chronic radiodermatitis (so-called roentgen-skin) of the interscapular space. In addition, two tumors were present in the upper and lower parts of the roentgen-skin. The upper tumor revealed adenoid basal cell epithelioma and the lower tumor was pigmented solid basal cell epithelioma. A view on the development of basal cell epitheliomas on the roentgen-skin was assumed as follows: When epidermal and adnexal cells suffer from a certain damage by X-ray, especially soft X-ray, these cells may become modulated cells which have the same functions as adult immature pluripotential cells. From these modulated cells, basal cell epitheliomas may develop. (author)

Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer.

Science.gov (United States)

Giessler, Klara M; Kleinheinz, Kortine; Huebschmann, Daniel; Balasubramanian, Gnana Prakash; Dubash, Taronish D; Dieter, Sebastian M; Siegl, Christine; Herbst, Friederike; Weber, Sarah; Hoffmann, Christopher M; Fronza, Raffaele; Buchhalter, Ivo; Paramasivam, Nagarajan; Eils, Roland; Schmidt, Manfred; von Kalle, Christof; Schneider, Martin; Ulrich, Alexis; Scholl, Claudia; Fröhling, Stefan; Weichert, Wilko; Brors, Benedikt; Schlesner, Matthias; Ball, Claudia R; Glimm, Hanno

2017-07-03

A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences. © 2017 Giessler et al.

PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

Science.gov (United States)

Li, Jiarong; Karaplis, Andrew C.; Huang, Dao C.; Siegel, Peter M.; Camirand, Anne; Yang, Xian Fang; Muller, William J.; Kremer, Richard

2011-01-01

Parathyroid hormone–related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer — it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention. PMID:22056386

Epidemiological profile of patients with malignant skin tumors at the plastic surgery secondary service in the countryside of São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Fernanda Simoneti

2016-07-01

Full Text Available Introduction: Non-melanoma skin tumor is the one with highest prevalence and incidence in Brazil, comprising squamous cell carcinoma (SCC and basal cell carcinoma (CBC. The main risk factor for the development of these tumors is chronic exposure to sunlight, justifying the most affected age group and anatomical locations. Treatment aims to excise the lesion with minimal deformity. Surgical excision with safe margins is the main therapeutic option; others depend on the number of lesions, location, histological type, general health and medical comorbidity. Objectives: To describe the epidemiological profile of patients with skin tumors; to identify the prevalence of non-melanoma; and to evaluate surgical margin. Methods: Observational, longitudinal and retrospective study of patients undergoing resection of suspicious lesions in secondary service. Results: We identified 140 lesions in 67 patients, 59% were male and 71.6% over 60 years of age. The most affected regions were head and neck (72.1%; 69.1% were CBC, 29.2% CBC, and 1.6% melanoma; 80.4% informed free margins, 7.3% indicated affected margins; the mean age of these patients was 75.2 years and the mean number of concomitant injuries was 8.7. The association was significant between female gender and presence of lesions <5 mm. Conclusions: The prevalence of lesions in elderly men (over 60 years is in accordance with the pattern described in literature. Free margins, which were obtained in most of the cases in this study, indicate therapeutic efficacy of the simple surgical excision. Marcroscopic margins adopted in the preoperative marking favor effectiveness, reserving Möhs surgery for recurrence or margin involvement. öhs para recidivas ou comprometimento de margem.

Morphological and clinical characteristics of the head epidermal skin carcinomas

Directory of Open Access Journals (Sweden)

Mijović M.

2015-01-01

Full Text Available The most common skin malignant tumor of the epidermoid origin are basal cell (BCC and squamous cell (SCC carcinoma. They occur at the photoexposed parts of the body in 90% of cases and are directly associated with skin damage caused by long term exposure to UV rays, usually in older persons and light skin. Almost 65,000 people die annually in the world from their consequences. The most important link in preventing the occurrence of these tumors is prevention, but their early identification allows adequate surgical treatment with sparing surrounding tissue. The main objective of this paper is to examine the histopathological and clinical-morphological characteristics of BCC and SCC of the skin of the head. The analysis included 439 cancer (297 (67.7% BCC, 126 (28.7% SCK and 16 (3.6% BCK + SCK, among which over 60% were diagnosed in men, usually in the seventh and eighth decade of life, with the highest incidence of BCC on the nose or on the skin of the upper half of the face and SCK on the lips or the skin of the lower half of face. All skin cancers of the head were more common on the right side. Clinical and morphological, most of the BCC were manifested by ulcerative form of average size 1.2cm and mixed histological type, and SCK by vegetative form of average size 1.55cm and histological grade I. The highest number of BCC and SCC was completly removed, in contrast to the combination of these two tumors among them in most cases the subsequent surgical intervention was necessary.

Dermal Delivery of Constructs Encoding Cre Recombinase to Induce Skin Tumors in PtenLoxP/LoxP;BrafCA/+ Mice

Directory of Open Access Journals (Sweden)

Marcel A. Deken

2016-12-01

Full Text Available Current genetically-engineered mouse melanoma models are often based on Tyr::CreERT2-controlled MAPK pathway activation by the BRAFV600E mutation and PI3K pathway activation by loss of PTEN. The major drawback of these models is the occurrence of spontaneous tumors caused by leakiness of the Tyr::CreERT2 system, hampering long-term experiments. To address this problem, we investigated several approaches to optimally provide local delivery of Cre recombinase, including injection of lentiviral particles, DNA tattoo administration and particle-mediated gene transfer, to induce melanomas in PtenLoxP/LoxP;BrafCA/+ mice lacking the Tyr::CreERT2 allele. We found that dermal delivery of the Cre recombinase gene under the control of a non-specific CAG promoter induced the formation of melanomas, but also keratoacanthoma and squamous cell carcinomas. Delivery of Cre recombinase DNA under the control of melanocyte-specific promoters in PtenLoxP/LoxP;BrafCA/+ mice resulted in sole melanoma induction. The growth rate and histological features of the induced tumors were similar to 4-hydroxytamoxifen-induced tumors in Tyr::CreERT2;PtenLoxP/LoxP;BrafCA/+ mice, while the onset of spontaneous tumors was prevented completely. These novel induction methods will allow long-term experiments in mouse models of skin malignancies.

Effect of hyperthermia on epithelial microneoplastic cell populations induced by irradiation of rat skin

International Nuclear Information System (INIS)

Gragtmans, N.J.; McGregor, J.F.

1983-01-01

Two groups of male rats of the Charles River CD stock received a dose of 1,600 rad beta-radiation (700 rad/min) on the skin of the dorsum. Two months later, the site of irradiation of one of the groups was treated with hyperthermia at 44 degrees C for 2.5 minutes. A third control group received only the hyperthermic treatment. Over 90% of the animals in the 2 irradiated groups developed skin tumors (benign and malignant epithelial) at the irradiated site. There was no significant difference between these 2 groups in incidence of animals with tumors, incidence of tumors, distribution of tumor types, or rate of tumor appearance. The incidence of animals with tumors in the control group was less than 4% at any time

Skin carcinomas: Radiobiological principles, radiotherapeutic techniques and clinical management

International Nuclear Information System (INIS)

Schmidt-Ullrich, Rupert K.; Johnson, Christopher R.

1997-01-01

Purpose/Objective: The course will be divided into three major topics: (1) Review of radiobiological principles as they apply to the radiotherapeutic management of skin carcinomas; (2) review of radiotherapeutic techniques including beam qualities, beam collimation, tissue dose profiles, and the relative indications of external beam irradiation vs. brachytherapy; (3) comprehensive review of the tumor biology of skin malignancies, including malignant melanoma, and of the relative indications for radiotherapeutic and/or surgical management. (1) Review of critical data which have led to currently applied principles of time-dose-volume concepts in the radiotherapeutic management of skin carcinomas. Emphasis will be placed on the relative importance of fraction size and overall treatment time on tumor control probability and acute and late normal tissue toxicity. (2) Considering that radiotherapy in the management of skin carcinomas is often used to minimize patient disfiguration and to preserve critical body functions (e.g. eye lids) the technical aspects of radiotherapy delivery are most critical. Careful evaluation of the extent of the lesions including evaluation of their depth of invasion will determine the quality of the radiation beams, orthovoltage and low energy electrons being the most useful. Beam harding for orthovoltage beams and secondary and tertiary (skin) collimation of appropriate electron beams are critical. For more extensive and deeply invasive lesions contour-shaping through customized bolus material is essential. Equally important is the familiarity with custom shielding of critical structures, such as eyes, ears, oral cavity and central nervous system structures. Brachytherapy applications in the treatment of skin carcinomas is limited but should be considered when implants with high dose uniformity can be constructed. (3) The discussion of clinical management will start with a discussion of properties and routes of spread of the diverse

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

Science.gov (United States)

Shmelkov, Sergey V.; Butler, Jason M.; Hooper, Andrea T.; Hormigo, Adilia; Kushner, Jared; Milde, Till; St. Clair, Ryan; Baljevic, Muhamed; White, Ian; Jin, David K.; Chadburn, Amy; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; D’Angelica, Michael; Kemeny, Nancy; Lyden, David; Rafii, Shahin

2008-01-01

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic

Clinical confrontation results of diagnostics and treatment of skin cancer

International Nuclear Information System (INIS)

Zikiryakhodjaev, D.Z.; Sanginov, D.R.

2001-01-01

In this chapter of book authors investigated the clinical confrontation results of diagnostics and treatment of skin cancer. They noted that diagnostic of skin cancer have to foresee the determination morphologic implements and degree of malignancy tumorous process why in general depend prognosis of illness

Problems with ink skin markings for radiation field setups

International Nuclear Information System (INIS)

Endoh, Masaru; Saeki, Mituaki; Ishida, Yusei

1982-01-01

Ink skin markings are used in radiation therapy to aid in reproduction of treatment field setups or to indelibly outline field markings or tumors. We reported two cases of indelible ink skin for radiation field septa with minimal discomfort and dermatitis have been experienced for 6 months and above since end of radiotherapy. These indelible ink skin markings look like tattoo that will be big problems in the case of young female. We improved these problems by using of 10 percent silver nitrate instead of habitual skin ink. (author)

Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice

DEFF Research Database (Denmark)

Kragh, M; Spang-Thomsen, M; Kristjansen, P E

1999-01-01

, 11, or 15 days after inoculation. The time from inoculation until initiation of exponential tumor growth was determined along with the post-therapeutic growth delay and the initial tumor doubling time (TD) for each individual tumor (n=103) on the basis of tumor volume growth curves. We found that: i......) the onset of growth of U87 xenografts was effectively inhibited by concurrent treatment with TNP-470 beyond the first three days after inoculation, ii) this effect was fully reversible upon termination of therapy, and iii) the post-therapeutic growth delay was independent of the accumulated dose...

Fractionated laser resurfacing corrects the inappropriate UVB response in geriatric skin.

Science.gov (United States)

Spandau, Dan F; Lewis, Davina A; Somani, Ally-Khan; Travers, Jeffrey B

2012-06-01

Non-melanoma skin cancer is a disease primarily afflicting geriatric patients as evidenced by the fact that 80% of all non-melanoma skin cancers are diagnosed in patients over the age of 60 years. As such, geriatric skin responds to cancer-inducing UVB irradiation in a manner that allows the establishment of tumor cells. Currently, the only effective treatment for non-melanoma skin cancer is the removal of the tumors after they appear, indicating the need for a more cost-effective prophylactic therapy. Geriatric volunteers were treated with fractionated laser resurfacing therapy on either sun-protected (upper buttocks) or chronically sun-exposed (dorsal forearm) skin. Fractionated laser resurfacing therapy was shown to decrease the occurrence of senescent fibroblasts in geriatric dermis, increase the dermal expression of IGF-1, and correct the inappropriate UVB response observed in untreated geriatric skin. These responses to fractionated laser resurfacing were equal to the effects seen previously using the more aggressive wounding following dermabrasion. Furthermore, fractionated laser resurfacing was equally effective in both sun-protected and sun-exposed skin. The ability of fractionated laser resurfacing treatment to protect against the occurrence of UVB-damaged proliferating keratinocytes indicates the potential of fractionated laser resurfacing to reduce or prevent aging-associated non-melanoma skin cancer.

Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.

Directory of Open Access Journals (Sweden)

Joseph G Skeate

Full Text Available Nano-Pulse Stimulation (NPS is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.

Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.

Science.gov (United States)

Skeate, Joseph G; Da Silva, Diane M; Chavez-Juan, Elena; Anand, Snjezana; Nuccitelli, Richard; Kast, W Martin

2018-01-01

Nano-Pulse Stimulation (NPS) is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16)-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS) to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s) associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.

The role of chronic acanthosis and subacute inflammation in tumor promotion in CD-1 mice by petroleum middle distillates.

Science.gov (United States)

Skisak, C

1991-07-01

An initiation-promotion bioassay using CD-1 mice was conducted to examine the role of chronic acanthosis and inflammation in tumor promotion by petroleum middle distillates (MD). Test groups were initiated with 7,12-dimethylbenz[a]anthracene (DMBA). Promotion with MD consisted of twice weekly treatments for 25 weeks with either 25 or 50 microliters, 50 microliters + daily treatment with 15 micrograms dexamethasone, 50 microliters + postapplication washings, or 100 microliters. Three mice from each group were euthanized at 21-day intervals (24 total per group). The skin from interim euthanized mice was examined histopathologically for tumors, acanthosis, and subacute inflammation. Tumor incidence at study termination was as follows: 25 microliters (45%), 50 microliters (43%), 50 microliters + dexamethasone (0%), 50 microliters + washing (70%), and 100 microliters (81%). A correlation of greater than 0.93 was observed at all intervals between tumor incidence and cumulative group mean degrees of acanthosis in interim euthanized mice. The correlation between subacute inflammation at early through midstudy interval weeks and tumor incidence at study termination was poor. These results support the hypothesis that induction of a lasting, albeit mild, hyperplasia is an essential, but not sufficient requirement for tumor promotion. Furthermore, subacute inflammation does not appear to be a significant factor in tumor promotion by petroleum MD.

Skin cancer associated with commonly prescribed drugs: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and statins -weighing the evidence.

Science.gov (United States)

Nardone, Beatrice; Orrell, Kelsey A; Vakharia, Paras P; West, Dennis P

2018-02-01

Skin cancers, including both malignant melanoma (MM) and nonmelanoma skin cancer (NMSC), are the most commonly diagnosed cancers in the US. The incidence of both MM and NMSC continues to rise. Areas covered: Current evidence for an association between four of the most commonly prescribed classes of drugs in the U.S. and risk for MM and NMSC is reported. Medline was searched (January 2000 to May 2017) for each drug in the classes and for 'basal cell carcinoma', 'squamous cell carcinoma', 'non-melanoma skin cancer', 'skin cancer' and 'melanoma'. Skin cancer risk information was reported for: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins). Expert opinion: Since skin cancer risk is associated with all four classes of these commonly prescribed drugs that represent nearly 20% of the Top 100 drugs in the U.S., these important findings warrant enhanced education, especially for prescribers and those patients at high risk for skin cancer.

Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

1983-03-01

A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

Canonical and Non-Canonical NF-κB Signaling Promotes Breast Cancer Tumor-Initiating Cells

Science.gov (United States)

Kendellen, Megan F.; Bradford, Jennifer W.; Lawrence, Cortney L.; Clark, Kelly S.; Baldwin, Albert S.

2014-01-01

Tumor-initiating cells (TICs) are a sub-population of cells that exhibit a robust ability to self-renew and contribute to the formation of primary tumors, the relapse of previously treated tumors, and the development of metastases. TICs have been identified in various tumors, including those of the breast, and are particularly enriched in the basal-like and claudin-low subtypes of breast cancer. The signaling pathways that contribute to the function and maintenance of TICs are under intense study. We explored the potential involvement of the NF-κB family of transcription factors in TICs in cell lines that are representative of basal-like and claudin-low breast cancer. NF-κB was found to be activated in breast cancer cells that form tumorspheres efficiently. Moreover, both canonical and non-canonical NF-κB signaling is required for these cells to self-renew in vitro and to form xenograft tumors efficiently in vivo using limiting dilutions of cells. Consistent with this, canonical and non-canonical NF-κB signaling is activated in TICs isolated from breast cancer cell lines. Experimental results indicate that NF-κB promotes the function of TICs by stimulating epithelial-to-mesenchymal transition (EMT) and by upregulating the expression of the inflammatory cytokines IL-1β and IL-6. The results suggest the use of NF-κB inhibitors for clinical therapy of certain breast cancers. PMID:23474754

Potential of confocal laser scanning microscopy for non-invasive diagnostics of malignant epithelial skin tumors in the course of dermatoheliosis progression

Directory of Open Access Journals (Sweden)

E. S. Snarskaya

2016-01-01

Full Text Available Most cases of malignant epithelial skin neoplasms including actinic keratosis and basal cell carcinoma, which are characterized by the most complicated course and numerous clinical and morphological options, involve dermatoheliosis progression. The risk of actinic keratosis transformation into basal cell carcinoma varies from 0.1% to 20% and up to 80% in cases of multiple AK lesion foci. A non-invasive method known as reflectance confocal laser scanning microscopy is the most promising one for the purposes of early diagnostics of signs pointing at epithelial skin neoplasm development and makes it possible to monitor the tumor in progress in vivo to diagnose the presence of a pool of squamous cells on a timely basis. The confocal laser scanning microscopy method provides high-contrast images of for any horizontal-oriented morphologic structures in the epidermis and upper dermis with a resolution comparable to those characteristic of traditional optical microscopy of skin tissue samples. According to our data obtained as a result of studying dynamic changes and morphologic structures in actinic keratosis foci (50 cases using the confocal laser scanning microscopy method, we discovered a number of morphologic features, and their further analysis will distinguish the signs of progressing carcinogenesis in case of dermatoheliosis.

Topical Curcumin-Based Cream Is Equivalent to Dietary Curcumin in a Skin Cancer Model

International Nuclear Information System (INIS)

Sonavane, K.; Phillips, J.; Lakshmaiah, R. R.; Ekshyyan, O.; Moore-Medlin, T.; Rong, X.; Nathan, C. O.; Ekshyyan, O.; Moore-Medlin, T.; Rong, X.; Nathan, C.O.; Gill, J. R.; Clifford, J. L.; Abreo, F.; Boudreaux, D.; Nathan, C. O.

2012-01-01

Skin squamous cell carcinoma (SCC), the most common cancer in the USA, is a growing problem with the use of tanning booths causing sun-damaged skin. Antiproliferative effects of curcumin were demonstrated in an aggressive skin cancer cell line SRB12-p9 (ρ< 0.05 compared to control). Topical formulation was as effective as oral curcumin at suppressing tumor growth in a mouse skin cancer model. Curcumin at 15 mg administered by oral, topical, or combined formulation significantly reduced tumor growth compared to control (ρ=0.004). Inhibition of pAKT, pS6, p-4EBP1, pSTAT3, and pERK 1/2 was noted in SRB12-p9 cells post-curcumin treatment compared to control (ρ<0.05). Inhibition of pSTAT3 and pERK 1/2 was also noted in curcumin-treated groups in vivo. IHC analysis revealed human tumor specimens that expressed significantly more activated pERK ( ρ=0.006) and pS6 (ρ< 0.0001) than normal skin samples. This is the first study to compare topical curcumin to oral curcumin. Our data supports the use of curcumin as a chemo preventive for skin SCC where condemned skin is a significant problem. Prevention strategies offer the best hope of future health care costs in a disease that is increasing in incidence due to increased sun exposure.

Skin invasion and prognosis in node negative breast cancer: a retrospective study

Directory of Open Access Journals (Sweden)

Horii Rie

2008-01-01

Full Text Available Abstract Background The impact of skin invasion in node negative breast cancer is uncertain. Methods We determined the prognosis in 97 node negative breast cancer patients (case group who had tumors with skin invasion. Then we compared these patients with 4500 node negative invasive breast cancer patients treated surgically in the same period. Results Patients with skin invasion tended to be older, had more invasive lobular carcinoma and larger tumor size, and were less likely to have breast conserving surgery than those in the control group. The 5-year disease-free survival rate in the case group was 94.0%. There was no significant difference in the 10-year disease-specific overall survival rates in terms of skin invasion in node negative patients (90.7% in the case group, 92.9% in the control group; p = 0.2032. Conclusion Results suggest that skin invasion has no impact on survival in node negative invasive breast cancer patients. The adjuvant regimens which the individual institute applies for node negative breast cancer should be used regardless of skin invasion.

ATF3 activates Stat3 phosphorylation through inhibition of p53 expression in skin cancer cells.

Science.gov (United States)

Hao, Zhen-Feng; Ao, Jun-Hong; Zhang, Jie; Su, You-Ming; Yang, Rong-Ya

2013-01-01

ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

Science.gov (United States)

Maytin, Edward V.; Anand, Sanjay

2016-03-01

In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

Targeting Tumor Oct4 to Deplete Prostate Tumor and Metastasis Initiating Cells

Science.gov (United States)

2017-12-01

is associated with androgen receptor (AR). We detected Oct4 protein expression in prostate cancer cells as well as in tumor tissue specimens...unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Identification of genes driving prostate carcinogenesis will lead to new cancer treatment. The human...a pseudogene of embryonic Oct4 (POU5F1). A recent study found that tumor Oct4 found in prostate cancer cells is due to the gene expression of POU5F1B

The first skin cancer screening day at the Italian parliament: a Euromelanoma initiative.

Science.gov (United States)

Suppa, Mariano; Neri, Luca; Bianchi, Luca; Capizzi, Rodolfo; Carbone, Angelo; Catricalà, Caterina; Chimenti, Sergio; Fargnoli, Maria Concetta; Fossati, Barbara; Frascione, Pasquale; Peris, Ketty

2015-01-01

The effort to decrease incidence/mortality of skin cancer should target not only the general public but also politicians and decision makers, to create a proper health policy. We report the results of the first Skin Cancer Screening Day at the Italian Parliament, organized to draw politicians' attention on skin cancer. A questionnaire was used to collect data on participants' characteristics and suspected skin cancers. We screened 70 members of parliament (61.4% males, median age 54 years). Overall skin cancer suspicion rate was 14.5%. Suspicion rate, detection rate, and positive predictive values for melanoma were respectively 1.6, 1.6, and 100%, and for basal cell carcinoma 6.5, 1.6, and 25%. Highly educated, parliament display sun-seeking behaviors similar to those previously described in the general public. Increasing politicians' attention on skin cancer is vital for sufficient resources to be allocated to prevention strategies. Expert medical groups and politicians should cooperate to create a proper, integrated policy on skin cancer. © 2014 The International Society of Dermatology.

Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

Science.gov (United States)

Testa, Ugo; Pelosi, Elvira; Castelli, Germana

2018-04-13

Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

Skin-safe photothermal therapy enabled by responsive release of acid-activated membrane-disruptive polymer from polydopamine nanoparticle upon very low laser irradiation.

Science.gov (United States)

Zhu, Rui; Gao, Feng; Piao, Ji-Gang; Yang, Lihua

2017-07-25

How to ablate tumor without damaging skin is a challenge for photothermal therapy. We, herein, report skin-safe photothermal cancer therapy provided by the responsive release of acid-activated hemolytic polymer (aHLP) from the photothermal polydopamine (PDA) nanoparticle upon irradiation at very low dosage. Upon skin-permissible irradiation (via an 850 nm laser irradiation at the power density of 0.4 W cm -2 ), the nanoparticle aHLP-PDA generates sufficient localized-heat to bring about mild hyperthermia treatment and consequently, responsively sheds off the aHLP polymer from its PDA nanocore; this leads to selective cytotoxicity to cancer cells under the acidic conditions of the extracellular microenvironment of tumor. As a result, our aHLP-PDA nanoparticle upon irradiation at a low dosage effectively inhibits tumor growth without damaging skin, as demonstrated using animal models. Effective in mitigating the otherwise inevitable skin damage in tumor photothermal therapy, the nanosystem reported herein offers an efficient pathway towards skin-safe photothermal therapy.

Malignant Glomus Tumor of the Peritoneum: Case Report

Energy Technology Data Exchange (ETDEWEB)

Baleato-González, Sandra; García-Figueiras, Roberto; Trujillo-Ariza, Maria Virginia [Department of Radiology, Complexo Hospitalario Universitario de Santiago de Compostela, Choupana s/n, 15701 Santiago de Compostela (A Coruña) (Spain); Carrera-Álvarez, Juan Jose [Department of Pathology, Complexo Hospitalario Universitario de Santiago de Compostela, Choupana s/n, 15701 Santiago de Compostela (A Coruña) (Spain)

2014-07-01

Glomus tumors are usually benign tumors that occur in the skin and soft tissues of the extremities. Visceral locations, such as stomach, intestines or lung, are extremely rare because glomus bodies are rare or absent in these organs. This report describes our experience in a 47-year-old woman diagnosed with a peritoneal malignant glomus tumor. This finding has not been previously reported.

Malignant Glomus Tumor of the Peritoneum: Case Report

International Nuclear Information System (INIS)

Baleato-González, Sandra; García-Figueiras, Roberto; Trujillo-Ariza, Maria Virginia; Carrera-Álvarez, Juan Jose

2014-01-01

Glomus tumors are usually benign tumors that occur in the skin and soft tissues of the extremities. Visceral locations, such as stomach, intestines or lung, are extremely rare because glomus bodies are rare or absent in these organs. This report describes our experience in a 47-year-old woman diagnosed with a peritoneal malignant glomus tumor. This finding has not been previously reported

Targeted two-photon PDT photo-sensitizers for the treatment of subcutaneous tumors

Science.gov (United States)

Spangler, C. W.; Rebane, A.; Starkey, J.; Drobizhev, M.

2009-06-01

New porphyrin-based photo-sensitizers have been designed, synthesized and characterized that exhibit greatly enhanced intrinsic two-photon absorption. These new photo-sensitizers have been incorporated into triad formulations that also incorporate Near-infrared (NIR) imaging agents, and small-molecule targeting agents that direct the triads to cancerous tumors' over-expressed receptor sites. PDT can be initiated deep into the tissue transparency window at 780-800 nm utilizing a regeneratively amplified Ti:sapphire laser using 100-150 fs pulses of 600-800 mW. Human tumor xenografts of human breast cancer (MDA-MB-231) and both small SCLC (NCI-H69) and NSCLC (A-459) have been successfully treated using octreotate targeting of over-expressed SST2 receptors. In particular, the lung cancer xenografts can be successfully treated by irradiating from the side of the mouse opposite the implanted tumor, thereby passing through ca. 2 cm of mouse skin, tissue and organs with no discernible damage to healthy tissue while causing regression in the tumors. These results suggest a new PDT paradigm for the noninvasive treatment of subcutaneous tumors, including the possibility that the targeting moiety could be matched to individual patient genetic profiles (patient-specific therapeutics).

Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

Science.gov (United States)

Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

2017-06-15

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Properties of internalization factors contributing to the uptake of extracellular DNA into tumor-initiating stem cells of mouse Krebs-2 cell line.

Science.gov (United States)

Dolgova, Evgeniya V; Potter, Ekaterina A; Proskurina, Anastasiya S; Minkevich, Alexandra M; Chernych, Elena R; Ostanin, Alexandr A; Efremov, Yaroslav R; Bayborodin, Sergey I; Nikolin, Valeriy P; Popova, Nelly A; Kolchanov, Nikolay A; Bogachev, Sergey S

2016-05-25

Previously, we demonstrated that poorly differentiated cells of various origins, including tumor-initiating stem cells present in the ascites form of mouse cancer cell line Krebs-2, are capable of naturally internalizing both linear double-stranded DNA and circular plasmid DNA. The method of co-incubating Krebs-2 cells with extracellular plasmid DNA (pUC19) or TAMRA-5'-dUTP-labeled polymerase chain reaction (PCR) product was used. It was found that internalized plasmid DNA isolated from Krebs-2 can be transformed into competent Escherichia coli cells. Thus, the internalization processes taking place in the Krebs-2 cell subpopulation have been analyzed and compared, as assayed by E. coli colony formation assay (plasmid DNA) and cytofluorescence (TAMRA-DNA). We showed that extracellular DNA both in the form of plasmid DNA and a PCR product is internalized by the same subpopulation of Krebs-2 cells. We found that the saturation threshold for Krebs-2 ascites cells is 0.5 μg DNA/10(6) cells. Supercoiled plasmid DNA, human high-molecular weight DNA, and 500 bp PCR fragments are internalized into the Krebs-2 tumor-initiating stem cells via distinct, non-competing internalization pathways. Under our experimental conditions, each cell may harbor 340-2600 copies of intact plasmid material, or up to 3.097 ± 0.044×10(6) plasmid copies (intact or not), as detected by quantitative PCR. The internalization dynamics of extracellular DNA, copy number of the plasmids taken up by the cells, and competition between different types of double-stranded DNA upon internalization into tumor-initiating stem cells of mouse ascites Krebs-2 have been comprehensively analyzed. Investigation of the extracellular DNA internalization into tumor-initiating stem cells is an important part of understanding their properties and possible destruction mechanisms. For example, a TAMRA-labeled DNA probe may serve as an instrument to develop a target for the therapy of cancer, aiming at elimination of

Modulation of miR-203 and its regulators as a function of time during the development of 7, 12 dimethylbenz [a] anthracene induced mouse skin tumors in presence or absence of the antitumor agents

International Nuclear Information System (INIS)

Tiwari, Prakash; Gupta, Krishna P.

2014-01-01

We investigated the chemopreventive effects of naturally occurring compounds like butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) individually or in combination in 7, 12-dimethylbenz [a] anthracene (DMBA) treated mouse skin at 4 and 16 weeks, the time before and after the tumor development. DMBA application did not show any skin tumors at 4 weeks but well defined tumors appeared at 16 weeks. BA, NA or CAG prevented the tumor development significantly but the protection was highly enhanced when all these compounds were given together. In order to see the molecular changes progressing with tumors, we showed the downregulation of tumor suppressor miR-203 at 16 weeks and upregulation of histone deacetylases (HDAC), DNA methyltransferase, promoter methylation of miR-203 at 4 or 16 weeks. Regulators of micro RNA biogenesis such as DICER1 and Ago2 were also deregulated by DMBA. Proto-oncogene c-myc and BMI1 were upregulated and tumor suppressor gene p16 was downregulated by DMBA as a function of time. Effects of BA, NA or CAG were more pronounced after 16 weeks as compared to 4 weeks in preventing the tumor development and altered gene expression. Concomitant administration of BA, NA and CAG tried to prevent these alterations more effectively than that of individual compound possibly by regulating miR-203 status through epigenetic or biogenetic modulations before and after the tumor development. Study provides a rationale for chemoprevention by combination of different compounds targeting miR-203. - Highlights: • DMBA modulates miR-203 and its regulator before and after the onset of tumors. • Suppression of miR-203 and p16 could be the result of gene promoter methylation. • BA, NA or CAG prevents the effects of DMBA. • Combination of BA, NA or CAG is more effective in preventing the DMBA modulations

Red tattoos, ultraviolet radiation and skin cancer in mice.

Science.gov (United States)

Lerche, Catharina M; Heerfordt, Ida M; Serup, Jørgen; Poulsen, Thomas; Wulf, Hans Christian

2017-11-01

Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red tattoos may be associated with increased risk of skin cancer due to potential carcinogens in tattoo inks. This combination has not been studied previously. Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back with a popular red tattoo ink. This often used ink is banned for use on humans because of high content of the potential carcinogen 2-anisidine. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. All UV-irradiated mice developed SCCs. The time to the onset of the first and second tumor was identical in the red-tattooed group compared with the control group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor appeared slightly faster in the red-tattooed group than in the controls (214 vs 224 days, P=.043). For the second and third tumor, the growth rate was faster in the red-tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs 38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin tattooed with a red ink containing 2-anisidine. However, red tattoos exposed to UVR showed faster tumor onset regarding the third tumor, and faster growth rate of the second and third tumor indicating red ink acts as a cocarcinogen with UVR. The cocarcinogenic effect was weak and may not be clinically relevant. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inflammatory microenvironment and tumor necrosis factor alpha as modulators of periostin and CCN2 expression in human non-healing skin wounds and dermal fibroblasts.

Science.gov (United States)

Elliott, Christopher G; Forbes, Thomas L; Leask, Andrew; Hamilton, Douglas W

2015-04-01

Non-healing skin wounds remain a significant clinical burden, and in recent years, the regulatory role of matricellular proteins in skin healing has received significant attention. Periostin and CCN2 are both upregulated at day 3 post-wounding in murine skin, where they regulate aspects of the proliferative phase of repair including mesenchymal cell infiltration and myofibroblast differentiation. In this study, we examined 1) the wound phenotype and expression patterns of periostin and CCN2 in non-healing skin wounds in humans and 2) the regulation of their expression in wound fibroblasts by tumor necrosis factor α (TNFα) and transforming growth factor-β1 (TGF-β1). Chronic skin wounds had a pro-inflammatory phenotype, characterized by macrophage infiltration, TNFα immunoreactivity, and neutrophil infiltration. Periostin, but not CCN2, was significantly suppressed in non-healing wound edge tissue at the mRNA and protein level compared with non-involved skin. In vitro, human wound edge fibroblasts populations were still able to proliferate and contract collagen gels. Compared to cells from non-involved skin, periostin and α-SMA mRNA levels increased significantly in the presence of TGF-β1 in wound cells and were significantly decreased by TNFα, but not those of Col1A2 or CCN2. In the presence of both TGF-β1 and TNFα, periostin and α-SMA mRNA levels were significantly reduced compared to TGF-β1 treated wound cells. Effects of TGF-β1 and TNFα on gene expression were also more pronounced in wound edge cells compared to non-involved fibroblasts. We conclude that variations in the expression of periostin and CCN2, are related to an inflammatory microenvironment and the presence of TNFα in human chronic wounds. Copyright © 2015. Published by Elsevier B.V.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

2013-02-15

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

International Nuclear Information System (INIS)

Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

2013-01-01

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside

Granular cell tumor: An uncommon benign neoplasm

Directory of Open Access Journals (Sweden)

Tirthankar Gayen

2015-01-01

Full Text Available Granular cell tumor is a distinctly rare neoplasm of neural sheath origin. It mainly presents as a solitary asymptomatic swelling in the oral cavity, skin, and rarely internal organs in the middle age. Histopathology is characteristic, showing polyhedral cells containing numerous fine eosinophilic granules with indistinct cell margins. We present a case of granular cell tumor on the back of a 48-year-old woman which was painful, mimicking an adnexal tumor.

Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.

Science.gov (United States)

Villanova, Federica; Flutter, Barry; Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O

2014-04-01

Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti-tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation.

Science.gov (United States)

Chu, Chung-Ching; Ali, Niwa; Karagiannis, Panagiotis; Di Meglio, Paola; Skowera, Ania; Napolitano, Luca; Barinaga, Guillermo; Grys, Katarzyna; Sharif-Paghaleh, Ehsan; Karagiannis, Sophia N; Peakman, Mark; Lombardi, Giovanna; Nestle, Frank O

2012-05-07

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.

Treatment of Implant Exposure due to Skin Necroses after Skin Sparing Mastectomy: Initial Experiences Using a Not Selective Random Epigastric Flap.

Science.gov (United States)

Echazarreta-Gallego, Estíbaliz; Pola-Bandrés, Guillermo; Arribas-Del Amo, María Dolores; Gil-Romea, Ismael; Sousa-Domínguez, Ramón; Güemes-Sánchez, Antonio

2017-10-01

Breast prostheses exposure is probably the most devastating complication after a skin sparing mastectomy (SSM) and implant-based, one-stage, breast reconstruction. This complication may occur in the immediate post-operative period or in the weeks and even months after the procedure. In most cases, the cause is poor skin coverage of the implant due to skin necrosis. Eight consecutive cases of implant exposure (or risk of exposure) due to skin necrosis in SSM patients over a period of 5 years, all patients were treated using a random epigastric rotation flap, executed by the same medical team. A random epigastric flap (island or conventional rotation flap) was used to cover the skin defect. All the patients completed the procedure and all prostheses were saved; there were no cases of flap necrosis or infection. Cases of skin necrosis after SSM and immediate implant reconstruction, in which the implant is at risk of exposure, can be successfully treated with a random epigastric rotation flap.

Statistical observations on postirradiation skin malignancies reported in Japan

Energy Technology Data Exchange (ETDEWEB)

Okazaki, Michiharu; Ogata, Katsumi; Inoue, Shouhei (Miyazaki Medical Coll., Kiyotake (Japan))

1989-01-01

A review was made on 412 cases of postirradiation skin malignancies reported in Japan up to March 1988. The ratio of male to female was 2:1. Histologically, squamous cell carcinoma occupied 60% of all cases. The incidence of sarcoma has recently been increased. Sixty percent of all skin malignancies resulted from irradiation for benign diseases. Radiotherapy has recently become the treatment of choice for malignancy. The incidence of malignancy resulting from occupational exposure has remained unchanged. The latency period before the development of radiation-induced malignancy varied in the following order with cause or primary disease: occupation>benign tumors>malignant tumors; and it varied with histology in the following order: basal cell epithelioma>squamous cell carcinoma>sarcoma. Malignant tumors treated with large doses of high energy photon beams were likely to develop sarcomas in a relatively short latency period of time. (N.K.).

Glomus tumor of penis- A rare case

Directory of Open Access Journals (Sweden)

Madhuri S. Kate

2013-01-01

Full Text Available Glomus tumors are rare, painful, and benign soft tissue tumors of the skin arising from the glomus body, an arteriovenous thermoregulatory structure. This lesion is usually found on the extremities. Glomus tumor involving the external genital organs including penis is extremely rare. Until now, only few cases have been reported in the available literature. A 22 year old male patient presented with a painful nodule over the penis. The pathologic diagnosis was glomus tumor of the glans penis. We report herewith a case of glomus tumor of penis diagnosed on histopathologic examination. Glomus tumor, being a benign neoplasm, complete extirpation of the glomus tumor is the treatment of choice.

Enhancement of skin tumorigenesis by cigarette smoke condensate following beta-irradiation in rats

International Nuclear Information System (INIS)

McGregor, J.F.

1982-01-01

The tumor-promoting ability of cigarette-smoke condensate (CSC) has been demonstrated in rat skin after beta-irradiation. Skin tumors from male albino Charles River CD rats (outbred Sprague-Dawley descended) were classified into 2 groups: carcinomas and other noncarcinoma tumors. A statistically significant increase (P less than 0.01) in tumor yield occurred after CSC treatment that began 2 months after irradiation. This finding confirmed our previously published pilot observation. Extension of the pilot experiment to obtain data on carcinoma yield and an experiment to observe the effects of CSC treatment beginning immediately after irradiation were performed. When CSC treatment began immediately after irradiation, the yield of noncarcinoma tumors was significantly reduced (P less than 0.01), whereas the carcinoma yield increased but statistically not significantly (P . 0.12). The increased yield of noncarcinoma tumors is attributed to a significant increase (P less than 0.01) of acute ulceration caused by CSC on recently irradiated skin. The increase in carcinoma yield resulted from an increase in the rate of conversion of noncarcinoma tumors to cancer. Carcinoma yield was also increased by CSC treatment beginning 2 months after irradiation, but the increase was not significant (P . 0.08). The lack of statistical significance for the carcinoma yields in both experiments may be ascribed to the insufficient number of cancers produced by the treatments. The relative ratios of cancer yields (1.7 and 2.5) did not differ greatly from the 2.2 ratio for the increase of noncarcinoma tumors. The possible relevance of the findings to human carcinogenesis is discussed

Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner

DEFF Research Database (Denmark)

Hald, Andreas; Eickhardt, Hanne; Maerkedahl, Rasmus Baadsgaard

2012-01-01

deficiency was due to thrombosis and lost patency of the tumor vasculature, resulting in tumor necrosis. The connection between plasmin-dependent fibrinolysis, vascular patency, and tumor growth was further substantiated as the effect of plasminogen deficiency on tumor growth could be reverted...

Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

Directory of Open Access Journals (Sweden)

Nina P Connolly

Full Text Available Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS virus / tumor virus receptor-A (tv-a transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

Polyradiomodification. Evaluation of the efficacy of the utilization of hyperglycemia in experimental hypoxiradiotherapy of tumors

International Nuclear Information System (INIS)

Kozin, S.V.; Dyuskaliev, Zh.D.; Yarmonenko, S.P.

1984-01-01

An experimental evaluation of the appropriateness of the use of short-term hyperglycemia combined with hypoxiradiotherapy of solid tumors is given. In comparing the response of tumors and overlying skin a conclusion has been made that gaseous hypoxia and the use of hyperglycemia separately yield in a considerable therapeutic benefit, and the use of the combination of these agents in some cases produces a greater therapeutic interval between tumor destruction and normal tissues. The mechanisms of the modification of radiation injuries of tumors and skin under the influence of the above two factors are discussed

Transgenic Overexpression of the Proprotein Convertase Furin Enhances Skin Tumor Growth

Directory of Open Access Journals (Sweden)

Jian Fu

2012-04-01

Full Text Available Furin, one of the members of the family of proprotein convertases (PCs, ubiquitously expressed as a type I membrane-bound proteinase, activates several proteins that contribute to tumor progression. In vitro studies using cancer cell lines and clinical specimens demonstrated that furin processes important substrates such as insulin-like growth factor 1 receptor (IGF-1R and transforming growth factor β, leading to increased tumor growth and progression. Despite the numerous studies associating furin with tumor development, its effects in preclinical models has not been comprehensively studied. In this study, we sought to determine the protumorigenic role of furin in vivo after a two-stage chemical carcinogenesis protocol in transgenic mice in which furin expression was targeted to the epidermal basal layer. We found that processing of the PC substrate IGF-1R and the proliferation rate of mouse epidermis was enhanced in transgenic mice when compared with their WT counterparts. Histopathologic diagnoses of the tumors demonstrated that furin transgenic mice (line F47 developed twice as many squamous carcinomas as the control, WT mice (P < .002. Similarly, tumors cells from transgenic mice were able to process PC substrates more efficiently than tumor cells from WT mice. Furthermore, furin expression resulted in a higher SCC volume in transgenic mice as well as an increase in the percentage of high-grade SCC, including poorly differentiated and spindle cell carcinomas. In conclusion, expression of furin in the basal layer of the epidermis increased tumor development and enhanced tumor growth, supporting the consideration of furin as a potential target for cancer treatment.

Giant cell tumor of the bone: aggressive case initially treated with denosumab and intralesional surgery

Energy Technology Data Exchange (ETDEWEB)

Von Borstel, Donald; Strle, Nicholas A. [Oklahoma State University Medical Center, Department of Radiology, Tulsa, OK (United States); Taguibao, Roberto A. [University of California, Irvine, UCI Medical Center, Department of Pathology, Orange, CA (United States); Burns, Joseph E. [University of California, Irvine, UCI Medical Center, Department of Radiological Sciences, Orange, CA (United States)

2017-04-15

Giant cell tumor of the bone (GCTB) is a locally aggressive benign tumor, which has historically been treated with wide surgical excision. We report a case of a 29-year-old male with histology-proven GCTB of the distal ulna. The initial imaging study was a contrast-enhanced magnetic resonance imaging (MRI) examination of the left wrist, which was from an outside facility performed before presenting to our institution. On the initial MRI, the lesion had homogenous T2-hyperintense and T1-hypointense signal with expansive remodeling of the osseous contour. A radiographic study performed upon presentation to our institution 1 month later showed progression of the lesion with atypical imaging characteristics. After confirming the diagnosis, denosumab therapy was implemented allowing for reconstitution of bone and intralesional treatment. The patient was treated with five doses of denosumab over the duration of 7 weeks. Therapeutic changes of the GCTB were evaluated by radiography and a post-treatment MRI. This MRI was interpreted as suspicious for worsening disease due to the imaging appearance of intralesional signal heterogeneity, increased perilesional fluid-like signal, and circumferential cortical irregularity. However, on subsequent intralesional curettage and bone autografting 6 weeks later, no giant cells were seen on the specimen. Thus, the appearance on the MRI, rather than representing a manifestation of lesion aggressiveness or a non-responding tumor, conversely represented the imaging appearance of a positive response to denosumab therapy. On follow-up evaluation, 5 months after intralesional treatment, the patient had recurrent disease and is now scheduled for wide-excision with joint prosthesis. (orig.)

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

Science.gov (United States)

Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Knee glomangioma: a rare location for a glomus tumor

Directory of Open Access Journals (Sweden)

Ricardo Gonçalves

2014-12-01

Full Text Available Glomus tumor is a rare, benign neoplasm rising from the glomus apparatus of the skin. It occurs most frequently on fingers and toes and accounts for 1.6% of all soft tissue tumors. Clinical diagnosis may prove difficult if the tumor occurs on an extra digital location. We report a case of a vascular-type glomus tumor (glomangioma found in an atypical location, namely the lateral aspect of the knee joint.

Skin cancers in elderly patients.

Science.gov (United States)

Malaguarnera, Giulia; Giordano, Maria; Cappellani, Alessandro; Berretta, Massimiliano; Malaguarnera, Michele; Perrotta, Rosario Emanuele

2013-11-01

Cancer in older people is a common problem worldwide. Among various types of cancer, skin cancers represent an important percentage. The principal risk factors are sun exposure, family history of skin cancer, fair skin color, but also the age plays an important role in the genesis of skin cancers. In older people there are a more prolonged exposure to carcinogenesis and a decreased functionality of reparation mechanisms of the cells so they acquire a selective advantage of growing and proliferating. At the same time age causes alteration in immune system by increasing NK-cells absolute number and decreasing both the endogenous and the lymphokine-induced lytic activities. The anti-tumor immune response is also mediated by the cytotoxic T- lymphocytes and in the elderly a strong reduction of T-cell function has been demonstrated. In elderly patients the diagnosis and the treatment of skin cancers can be different from younger counterpart. For example in older patients with melanoma is important to evaluate Breslow depth while higher mitotic rate has major value in younger patients. Moreover, the treatment should consider the performance status of patients and their compliance.

CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

Directory of Open Access Journals (Sweden)

Mihalescu-Maingot Maria

2010-02-01

Full Text Available Abstract Background Tumor initiating cells (TICs provide a new paradigm for developing original therapeutic strategies. Methods We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. Results A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs. Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Conclusions Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

International Nuclear Information System (INIS)

Patru, Cristina; Berhneim, Alain; Mihalescu-Maingot, Maria; Haiech, Jacques; Bièche, Ivan; Moura-Neto, Vivaldo; Daumas-Duport, Catherine; Junier, Marie-Pierre; Chneiweiss, Hervé; Romao, Luciana; Varlet, Pascale; Coulombel, Laure; Raponi, Eric; Cadusseau, Josette; Renault-Mihara, François; Thirant, Cécile; Leonard, Nadine

2010-01-01

Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies. We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies

Percutaneous absorption and skin decontamination of PCBs: In vitro studies with human skin and in vivo studies in the rhesus monkey

International Nuclear Information System (INIS)

Wester, R.C.; Maibach, H.I.; Bucks, D.A.; McMaster, J.; Mobayen, M.; Sarason, R.; Moore, A.

1990-01-01

Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing

Immune response to uv-induced tumors: transplantation immunity and lymphocyte populations exhibiting anti-tumor activity

International Nuclear Information System (INIS)

Streeter, P.R.

1985-01-01

Ultraviolet light-induced murine skin tumors were analyzed for their ability to induce tumor-specific and cross-protective transplantation immunity in immunocompetent syngeneic mice. These studies revealed that progressor UV-tumors, like regressor UV-tumors, possess tumor-specific transplantation antigens. Cross-protective transplantation immunity to UV-tumors, however, was associated with sensitization to the serum used to culture the tumor lines rather than to cross-reactive or common determinants on UV-tumors. An analysis of the cytolytic activity of lymphocytes from the spleens of mice immunized with either regressor or progressor UV-tumors revealed a striking difference between the two immune splenocyte populations. From regressor tumor-immune animals, cytolytic T (Tc) lymphocytes with specificity for the immunizing tumor were found. However, the analysis of splenic lymphocytes from progressor tumor immune animals revealed no such effector cells. To more effectively examine those lymphocytes exhibiting cytolytic activity in vitro, T lymphocyte cloning technology was used as a means of isolating homogeneous lymphocyte populations with the effector activities described above. The mechanisms where NK cells and other nonspecific effector cells could be induced in tumor-immune animals are discussed in the context of class II restricted immune responses

PDT for malignant tumors: a clinical analysis of 152 cases

Science.gov (United States)

Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

1993-03-01

Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

Management of Skin Cancer in the High-Risk Patient.

Science.gov (United States)

Behan, James W; Sutton, Adam; Wysong, Ashley

2016-12-01

Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.

Science.gov (United States)

Kemp, Michael G; Spandau, Dan F; Travers, Jeffrey B

2017-02-26

The growing incidence of non-melanoma skin cancer (NMSC) necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV) wavelengths of sunlight and age. Whereas UV radiation (UVR) has long been known to generate photoproducts in genomic DNA that promote genetic mutations that drive skin carcinogenesis, the mechanism by which age contributes to disease pathogenesis is less understood and has not been sufficiently studied. In this review, we highlight studies that have considered age as a variable in examining DNA damage responses in UV-irradiated skin and then discuss emerging evidence that the reduced production of insulin-like growth factor-1 (IGF-1) by senescent fibroblasts in the dermis of geriatric skin creates an environment that negatively impacts how epidermal keratinocytes respond to UVR-induced DNA damage. In particular, recent data suggest that two principle components of the cellular response to DNA damage, including nucleotide excision repair and DNA damage checkpoint signaling, are both partially defective in keratinocytes with inactive IGF-1 receptors. Overcoming these tumor-promoting conditions in aged skin may therefore provide a way to lower aging-associated skin cancer risk, and thus we will consider how dermal wounding and related clinical interventions may work to rejuvenate the skin, re-activate IGF-1 signaling, and prevent the initiation of NMSC.

Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin

Directory of Open Access Journals (Sweden)

Michael G. Kemp

2017-02-01

Full Text Available The growing incidence of non-melanoma skin cancer (NMSC necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV wavelengths of sunlight and age. Whereas UV radiation (UVR has long been known to generate photoproducts in genomic DNA that promote genetic mutations that drive skin carcinogenesis, the mechanism by which age contributes to disease pathogenesis is less understood and has not been sufficiently studied. In this review, we highlight studies that have considered age as a variable in examining DNA damage responses in UV-irradiated skin and then discuss emerging evidence that the reduced production of insulin-like growth factor-1 (IGF-1 by senescent fibroblasts in the dermis of geriatric skin creates an environment that negatively impacts how epidermal keratinocytes respond to UVR-induced DNA damage. In particular, recent data suggest that two principle components of the cellular response to DNA damage, including nucleotide excision repair and DNA damage checkpoint signaling, are both partially defective in keratinocytes with inactive IGF-1 receptors. Overcoming these tumor-promoting conditions in aged skin may therefore provide a way to lower aging-associated skin cancer risk, and thus we will consider how dermal wounding and related clinical interventions may work to rejuvenate the skin, re-activate IGF-1 signaling, and prevent the initiation of NMSC.

Gender affects skin wound healing in plasminogen deficient mice.

Directory of Open Access Journals (Sweden)

Birgitte Rønø

Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

Science.gov (United States)

Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

2016-01-01

Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

Loss of a putative tumor suppressor locus after gamma-ray-induced neoplastic transformation of HeLa x Skin fibroblast human cell hybrids

International Nuclear Information System (INIS)

Mendonca, M.S.; Redpath, J.L.; Fasching, C.L.

1995-01-01

The nontumorigenic HeLa x skin fibroblast hybrid cell line, CGL1, can be induced to re-express HeLa tumor-associated cell surface antigen, p75-IAP (intestinal alkaline phosphatase), with resulting neoplastic transformation, by exposure to γ radiation. This has allowed the human hybrid system to be developed into a quantitative in vitro model for radiation-induced neoplastic transformation of human cells. Recently, several γ-ray-induced IAP-expression mutants (GIMs) of the nontumorigenic HeLa x skin fibroblast hybrid CGL1 were isolated and all were tumorigenic when injected subcutaneously into nude mice. Control cell lines which were negative for p75-IAP (CONs) were also isolated from irradiated populations, and none were found to be tumorigenic. We have now begun to investigate the molecular basis of radiation-induced neoplastic transformation in this system by studying the potential genetic linkage between p75/IAP expression, tumorigenicity and damage to a putative tumor suppressor locus on fibroblast chromosome 11. Previous analysis of rare spontaneous segregants has indicated that this locus is involved in the regulation of tumorigenicity and in the expression of the HeLa tumor-associated cell surface marker intestinal alkaline phosphatase (p75-IAP) in this system. Therefore, analysis by restriction fragment length polymorphism and chromosome painting have been performed for chromosome 11, and for chromosome 13 as a control, for the p75/IAP-positive GIM and p75/IAP-negative CON cell lines. We report that in five of eight of the GIMs large-scale damage to the fibroblast chromosome 11's is evident (four GIMs have lost one complete copy of a fibroblast chromosome 11 heavily damaged). None of the CONs, however (0/5), have lost a complete copy of either fibroblast chromosome 11. No large-scale damage to the control chromosome 13's was detected in the GIMs or CONs. 49 refs., 3 figs., 2 tabs

Involvement of activation-induced cytidine deaminase in skin cancer development.

Science.gov (United States)

Nonaka, Taichiro; Toda, Yoshinobu; Hiai, Hiroshi; Uemura, Munehiro; Nakamura, Motonobu; Yamamoto, Norio; Asato, Ryo; Hattori, Yukari; Bessho, Kazuhisa; Minato, Nagahiro; Kinoshita, Kazuo

2016-04-01

Most skin cancers develop as the result of UV light-induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus-dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics.

Endocrine actions of vitamin D in skin: Relevance for photocarcinogenesis of non-melanoma skin cancer, and beyond.

Science.gov (United States)

Reichrath, Jörg; Saternus, Roman; Vogt, Thomas

2017-09-15

The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH) 2 D 3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH) 2 D 3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH) 2 D 3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR). Recent findings convincingly support the concept of a new function of the VDR as a tumor suppressor in skin, with key components of the vitamin D endocrine system, including VDR, CYP24A1, CYP27A1, and CYP27B1 being strongly expressed in non-melanoma skin cancer (NMSC). It has now been shown that anti-tumor effects of VDR, that include some of its ligand-induced growth-regulatory effects, are at least in part mediated by interacting in a highly coordinated manner with the p53 family (p53/p63/p73) in response to a large number of alterations in cell homeostasis, including UV-induced DNA damage, a hallmark for skin photocarcinogenesis. Considering the relevance of the vitamin D endocrine system for carcinogenesis of skin cancer, it is not surprising that low 25(OH)D serum concentrations and genetic variants (SNPs) of the vitamin D endocrine system have been identified as potential risk factors for occurrence and prognosis of skin malignancies. In conclusion, an increasing body of evidence now convincingly supports the concept that the vitamin D endocrine system is of relevance for photocarcinogenesis and progression of NMSC and that its pharmacologic modulation by vitamin D, 1,25(OH) 2 D 3, and analogs represents a promising new strategy for prevention and/or treatment of these malignancies. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of radiolabelled compound using reactor produced RI - Development of Ho-166 skin patch for treatment of skin cancer

Energy Technology Data Exchange (ETDEWEB)

Park, Kyung Bae [Korea Atomic Energy Research Institute, Taejon (Korea); Ryu, Jei Man [Dong Wha Pharm. Ind. Co., Ltd., Seoul (Korea)

1999-04-01

A radioactive patch which can be treat the skin cancer by direct irradiation was prepared by blending Ho(NO{sub 3}){sub 3}, 5H{sub 2}O and polyurethane(PU) and then irradiating with neutron in the nuclear reactor. The blend formation of the film was fonfirmed by FT-IR. Degree of the distribution of holmium and solvent in remaining in the film was determined. Physical properties of the film by thermal analysis, mechanical measurement and surface analysis were characterized, respectively. To evaluate efficacy of the patch, it was applied to the tumor surface of the hairlessmous. Until 6 weeks of the patch treatment 7 mice with skin tumor were cured totally (7/13). And the other nuclear except for holmium was in patch was not detected. Furthermore, the patch was stable at room temperature, 40 deg C and 60 deg C. (author). 17 refs., 13 figs., 9 tabs.

Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

Science.gov (United States)

Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

2018-02-01

The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

Dendritic cells: biology of the skin

NARCIS (Netherlands)

Toebak, M.J.; Gibbs, S.; Bruynzeel, D.P.; Scheper, R.J.; Rustemeyer, T.

2009-01-01

Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo

Two different approaches in skin cancer therapy: using a photosensitizer/a natural product

Science.gov (United States)

Abraham, Annie; Gayathri, Devi D.; Cibin, T. R.; Ramaiah, D.

2010-02-01

This paper deals with two potential modes for the treatment of skin cancer-one a novel approach using a squaraine dye and the other using a natural product- the flavonoid fraction of Saraca asoka. Squaraine dye is a photosensitizing agent, which is preferentially taken up and retained by the tumor cells and when irradiated with high power visible light results in the selective destruction of the tumor cells by photodynamic therapy. The uniqueness of this mode of treatment lies in the selective destruction of tumor cells without affecting the neighbouring normal cells, which is much advantageous over radiation therapy now frequently used. The chemopreventive and therapeutic effects of the plant component are explored as well. The experimental models were Swiss albino mice in which skin tumor was induced by DMBA. Marked reduction in tumor volume and burden in the treated groups were observed. The reversal of biochemical enzyme markers like rhodanese, myeloperoxidase, β-D glucuronidase, lactate dehydrogenase, hexokinase and sialic acid to near normal levels were observed in the PDT and flavonoid fraction treated groups. The live photographs of the experimental animals and histopathological data further support the obtained results. The study assumes importance as it combines a traditional treatment mode and a novel aspect in cancer therapy using the same experimental models. Also this is the first report on PDT using a squaraine dye for skin cancer therapy in vivo.

Oncogenic Radiation Abscopal Effects In Vivo: Interrogating Mouse Skin

International Nuclear Information System (INIS)

Mancuso, Mariateresa; Leonardi, Simona; Giardullo, Paola; Pasquali, Emanuela; Tanori, Mirella; De Stefano, Ilaria; Casciati, Arianna; Naus, Christian C.; Pazzaglia, Simonetta; Saran, Anna

2013-01-01

Purpose: To investigate the tissue dependence in transmission of abscopal radiation signals and their oncogenic consequences in a radiosensitive mouse model and to explore the involvement of gap junction intercellular communication (GJIC) in mediating radiation tumorigenesis in off-target mouse skin. Methods and Materials: Patched1 heterozygous (Ptch1 +/− ) mice were irradiated at postnatal day 2 (P2) with 10 Gy of x-rays. Individual lead cylinders were used to protect the anterior two-thirds of the body, whereas the hindmost part was directly exposed to radiation. To test the role of GJICs and their major constituent connexin43 (Cx43), crosses between Ptch1 +/− and Cx43 +/− mice were similarly irradiated. These mouse groups were monitored for their lifetime, and skin basal cell carcinomas (BCCs) were counted and recorded. Early responses to DNA damage - Double Strand Breaks (DSBs) and apoptosis - were also evaluated in shielded and directly irradiated skin areas. Results: We report abscopal tumor induction in the shielded skin of Ptch1 +/− mice after partial-body irradiation. Endpoints were induction of early nodular BCC-like tumors and macroscopic infiltrative BCCs. Abscopal tumorigenesis was significantly modulated by Cx43 status, namely, Cx43 reduction was associated with decreased levels of DNA damage and oncogenesis in out-of-field skin, suggesting a key role of GJIC in transmission of oncogenic radiation signals to unhit skin. Conclusions: Our results further characterize the nature of abscopal responses and the implications they have on pathologic processes in different tissues, including their possible underlying mechanistic bases

Oncogenic Radiation Abscopal Effects In Vivo: Interrogating Mouse Skin

Energy Technology Data Exchange (ETDEWEB)

Mancuso, Mariateresa, E-mail: mariateresa.mancuso@enea.it [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA), Casaccia Research Centre, Rome (Italy); Leonardi, Simona [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA), Casaccia Research Centre, Rome (Italy); Giardullo, Paola; Pasquali, Emanuela [Department of Radiation Physics, Guglielmo Marconi University, Rome (Italy); Tanori, Mirella [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA), Casaccia Research Centre, Rome (Italy); De Stefano, Ilaria [Department of Radiation Physics, Guglielmo Marconi University, Rome (Italy); Casciati, Arianna [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA), Casaccia Research Centre, Rome (Italy); Naus, Christian C. [Department of Cellular and Physiological Sciences, The Life Sciences Institute, University of British Columbia, Vancouver, British Columbia (Canada); Pazzaglia, Simonetta; Saran, Anna [Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l' Energia e lo Sviluppo Economico Sostenibile (ENEA), Casaccia Research Centre, Rome (Italy)

2013-08-01

Purpose: To investigate the tissue dependence in transmission of abscopal radiation signals and their oncogenic consequences in a radiosensitive mouse model and to explore the involvement of gap junction intercellular communication (GJIC) in mediating radiation tumorigenesis in off-target mouse skin. Methods and Materials: Patched1 heterozygous (Ptch1{sup +/−}) mice were irradiated at postnatal day 2 (P2) with 10 Gy of x-rays. Individual lead cylinders were used to protect the anterior two-thirds of the body, whereas the hindmost part was directly exposed to radiation. To test the role of GJICs and their major constituent connexin43 (Cx43), crosses between Ptch1{sup +/−} and Cx43{sup +/−} mice were similarly irradiated. These mouse groups were monitored for their lifetime, and skin basal cell carcinomas (BCCs) were counted and recorded. Early responses to DNA damage - Double Strand Breaks (DSBs) and apoptosis - were also evaluated in shielded and directly irradiated skin areas. Results: We report abscopal tumor induction in the shielded skin of Ptch1{sup +/−} mice after partial-body irradiation. Endpoints were induction of early nodular BCC-like tumors and macroscopic infiltrative BCCs. Abscopal tumorigenesis was significantly modulated by Cx43 status, namely, Cx43 reduction was associated with decreased levels of DNA damage and oncogenesis in out-of-field skin, suggesting a key role of GJIC in transmission of oncogenic radiation signals to unhit skin. Conclusions: Our results further characterize the nature of abscopal responses and the implications they have on pathologic processes in different tissues, including their possible underlying mechanistic bases.

SOLAR ULTRAVIOLET EXPOSURE AND MORTALITY FROM SKIN TUMORS

Science.gov (United States)

Berwick, Marianne; Pestak, Claire; Thomas, Nancy

2015-01-01

Solar UV radiation (UVR) exposure is clearly associated with increased mortality from nonmelanoma skin cancer—usually squamous cell carcinoma. However, the association with cutaneous melanoma is unclear from the evidence in ecologic studies and several analytic studies have conflicting results regarding the effect of high levels of intermittent UV exposure prior to diagnosis on mortality. Understanding this conundrum is critical to present coherent public health messages and to improve the mortality rates from melanoma. PMID:25207375

Successful Preoperative Chemoembolization in the Treatment of a Giant Malignant Phyllodes Tumor

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Kazuki, E-mail: kazkik1980@gmail.com; Mimura, Hidefumi; Arai, Yasunori [St. Marianna University School of Medicine, Department of Radiology (Japan); Doi, Masatomo [St. Marianna University School of Medicine, Department of Pathology (Japan); Kojima, Yasuyuki; Tsugawa, Koichiro [St. Marianna University School of Medicine, Division of Breast and Endocrine Surgery, Department of Surgery (Japan); Nakajima, Yasuo [St. Marianna University School of Medicine, Department of Radiology (Japan)

2016-07-15

The malignant phyllodes tumor is a relatively rare neoplasm and has not previously been a therapeutic target of interventional radiology. Herein, we report a successful case of preoperative chemoembolization of a giant malignant phyllodes tumor. The objective was to achieve sufficient tumor shrinkage before surgery to avoid the requirement for skin grafting after resection. Intra-arterial epirubicin infusion and subsequent embolization with Embosphere Microspheres (BioSphere Medical, Rockland, MA, USA) was undertaken three times over the course of 6 weeks and was well tolerated. The patient underwent surgery without skin grafting. Neither local recurrence nor distant metastasis was observed at 6 months after surgery.

Successful Preoperative Chemoembolization in the Treatment of a Giant Malignant Phyllodes Tumor

International Nuclear Information System (INIS)

Hashimoto, Kazuki; Mimura, Hidefumi; Arai, Yasunori; Doi, Masatomo; Kojima, Yasuyuki; Tsugawa, Koichiro; Nakajima, Yasuo

2016-01-01

The malignant phyllodes tumor is a relatively rare neoplasm and has not previously been a therapeutic target of interventional radiology. Herein, we report a successful case of preoperative chemoembolization of a giant malignant phyllodes tumor. The objective was to achieve sufficient tumor shrinkage before surgery to avoid the requirement for skin grafting after resection. Intra-arterial epirubicin infusion and subsequent embolization with Embosphere Microspheres (BioSphere Medical, Rockland, MA, USA) was undertaken three times over the course of 6 weeks and was well tolerated. The patient underwent surgery without skin grafting. Neither local recurrence nor distant metastasis was observed at 6 months after surgery.

Skin hydration, microrelief and greasiness of normal skin in Antarctica.

Science.gov (United States)

Tsankov, N; Mateev, D; Darlenski, R

2018-03-01

The skin is the primary defence of the human body against external factors from physical, chemical, mechanical and biologic origin. Climatic factors together with low temperature and sun radiation affect the skin. The effect of climatic conditions in Antarctica on healthy skin has not been previously addressed. The aim of this study was to evaluate the changes in the skin hydration, greasiness and microrelief due to the extreme climatic environmental factors during the stay of the members of the Bulgarian Antarctic expedition. Fifty-nine Caucasian healthy subjects, 42 men and 17 women with mean age 50.9 years (27-68), were enrolled. The study was performed in five consecutive years from 2011 to 2016 at the Bulgarian Antarctic base camp at Livingston Island. The study protocol consisted of two parts: study A: duration of 15 days with measurement of skin physiology parameters on a daily basis, and study B: five measurements at baseline and at days 14, 30, 45 and 50 upon arrival in Antarctica. We measured three biophysical parameters related to skin physiology at cheek skin by an impedance measuring device. No statistically significant difference between parameters at the different measurement points. There is a variation in skin hydration reaching its lower point at day 11 and then returning to values similar to baseline. Initially, an increase in skin greasiness was witnessed with a sharp depression at day 11 and final values at day 15 resembling the ones at baseline. An increase, although not statistically significant, in skin roughness was observed in the first 15 days of the study. Study B showed no statistically significant variances between values of the three parameters. Our studies show the pioneer results of the effect of Antarctic climate on human skin physiology. © 2017 European Academy of Dermatology and Venereology.

Elevated c-Src and c-Yes expression in malignant skin cancers

Directory of Open Access Journals (Sweden)

Lee Jang

2010-08-01

Full Text Available Abstracts Background Src family kinases (SFKs play an important role in cancer proliferation, survival, motility, invasiveness, metastasis, and angiogenesis. Among the SFKs, c-Src and c-Yes are particularly over-expressed or hyper-activated in many human epithelial cancers. However, only a few studies have attempted to define the expression and role of c-Src and c-Yes in cutaneous carcinomas. Objectives To investigate the expression of c-Src and c-Yes in cutaneous carcinomas to include malignant melanoma (MM, squamous cell carcinoma (SCC and basal cell carcinoma (BCC. Methods We examined 6 normal skin tissues and 18 malignant skin tumor tissues using western blotting for the expression of c-Src and c-Yes. In another set, 16 specimens of MM, 16 SCCs and 16 BCCs were analyzed for the expression of c-Src and c-Yes using immunohistochemical staining. Results Western blotting showed that c-Src was expressed in all malignant skin tumors, but not in normal skin, while c-Yes was expressed in MM and SCC, but not in BCC and normal skin. Immunohistochemical staining results of c-Src and c-Yes in MM, SCC, and BCC mirrored those of the western blot analysis. Conclusions c-Src, rather than c-Yes, plays a key role in the proliferation and progression of malignant skin cancers.

The oncogenic action of ionizing radiation on rat skin: Progress report, February 1, 1987-January 31, 1988

International Nuclear Information System (INIS)

Burns, F.J.

1987-01-01

The work outlined in this report includes: epidermal DNA strand breaks and radiation penetration; activation of oncogenes in radiation induced rat skin tumors; and rat skin carcinogenesis by neon ions. The effect of radiation penetration on DNA single strand breaks has been studied extensively in rat and mouse epidermis. The results show clearly that the number of strand breaks per unit dose in the epidermal DNA is reduced by 50% to 65% when the radiation penetration is reduced from 1.0 mm to 0.2 mm. This penetration effect on DNA strand breaks was not seen in mouse epidermal cell lines growing in plastic dishes. The results imply that DNA strand breakage in superficial cells is partially dependent on the radiation dose to underlying tissue. The phenomenon is not mediated by systemic interactions as it was observed in irradiated explanted skin. The oncogene activation pattern in the radiation-induced skin tumors was found to be tumor dependent. Either K-ras activation or c-myc amplification or both was observed in each tumor analyzed so far. Even benign fibromas exhibited c-myc amplification. The carcinogenicity of high penetration electrons (2.0 MeV) was determined in preparation for similar studies with a neon ion beam at the Berkeley Bevelac. The principal finding so far is a large excess of connective tissue tumors, fibromas (benign) and sarcomas (malignant). 59 refs., 1 tab

Computed tomography in diagnosis of skin tumors

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Sunao; Yamashita, Noriko; Hidano, Akira; Kohno, Atsushi (Tokyo Women' s Medical Coll. (Japan))

1983-02-01

There has been no report of CT study in the dermatological field. CT was performed on 10 cases of cutaneous and subcutaneous tumors (2 of steatoma, 2 of atheroma, 2 of calcified epithelioma, 1 of basal cell cancer, and 3 of angioma); and in some of them, this method appeared to be useful for diagnosis. In each case, a clinical picture and CT findings were compared, and further application of CT was discussed.

Immune response to UV-induced tumors: mediation of progressor tumor rejection by natural killer cells

International Nuclear Information System (INIS)

Streeter, P.R.; Fortner, G.W.

1986-01-01

Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic animals. In the present study, the authors compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either regressor or progressor UV-tumors. The results of this comparison implicated tumor-specific cytolytic T (Tc) lymphocytes in rejection of regressor UV-tumors, and revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific Tc cells even as the tumors rejected. Following in vitro resensitization of spleen cells from either regressor or progressor tumor immune animals, the authors found NK-like lymphocytes with anti-tumor activity. As the authors had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, the authors examined lymphocytes from the local tumor environment during the course of progressor tumor rejection for this activity. This analysis revealed NK lymphocytes exhibiting significant levels of cytolytic activity against UV-tumors. These results implicate NK cells as potential effector cells in the rejection of progressor UV-tumors by immune animals, and suggests that these cells may be regulated by T lymphocytes

A Case Report: Krukenberg Tumour with Nodular Skin Lesions

Directory of Open Access Journals (Sweden)

Özden Demir

2017-03-01

Full Text Available The Krukenberg tumor is a rare variety of metastatic cancer to the ovary. The stomach is the most common site for the primary tumor, followed by the breast, gall bladder, colon and pancreas. It is not always possible to distinguish ovarian metastasis from primary ovarian masses in patients in whom the malignancy center is unidentified. This case report firstly aims to present a patient who presented with common nodular skin lesions, migrating arthritis and severe clinical characteristics, and diagnosed with Krukenberg tumor with further examinations.

Hyperspectral signature analysis of skin parameters

Science.gov (United States)

Vyas, Saurabh; Banerjee, Amit; Garza, Luis; Kang, Sewon; Burlina, Philippe

2013-02-01

The temporal analysis of changes in biological skin parameters, including melanosome concentration, collagen concentration and blood oxygenation, may serve as a valuable tool in diagnosing the progression of malignant skin cancers and in understanding the pathophysiology of cancerous tumors. Quantitative knowledge of these parameters can also be useful in applications such as wound assessment, and point-of-care diagnostics, amongst others. We propose an approach to estimate in vivo skin parameters using a forward computational model based on Kubelka-Munk theory and the Fresnel Equations. We use this model to map the skin parameters to their corresponding hyperspectral signature. We then use machine learning based regression to develop an inverse map from hyperspectral signatures to skin parameters. In particular, we employ support vector machine based regression to estimate the in vivo skin parameters given their corresponding hyperspectral signature. We build on our work from SPIE 2012, and validate our methodology on an in vivo dataset. This dataset consists of 241 signatures collected from in vivo hyperspectral imaging of patients of both genders and Caucasian, Asian and African American ethnicities. In addition, we also extend our methodology past the visible region and through the short-wave infrared region of the electromagnetic spectrum. We find promising results when comparing the estimated skin parameters to the ground truth, demonstrating good agreement with well-established physiological precepts. This methodology can have potential use in non-invasive skin anomaly detection and for developing minimally invasive pre-screening tools.

Indian Hedgehog Controls Proliferation and Differentiation in Skin Tumorigenesis and Protects against Malignant Progression

Directory of Open Access Journals (Sweden)

Parisa Kakanj

2013-07-01

Full Text Available Mutations in the hedgehog pathway drive the formation of tumors in many different organs, including the development of basal cell carcinoma in the skin. However, little is known about the role of epidermal Indian hedgehog (Ihh in skin physiology. Using mouse genetics, we identified overlapping and distinct functions of Ihh in different models of epidermal tumorigenesis. Epidermal deletion of Ihh resulted in increased formation of benign squamous papilloma. Strikingly, Ihh-deficient mice showed an increase in malignant squamous cell carcinoma and developed lung and lymph node metastases. In a sebaceous gland tumor model, Ihh deficiency inhibited tumor cell differentiation. More mechanistically, IHH stimulated cell proliferation by activating the transcription factor GLI2 in human keratinocytes and human tumors. Thus, our results uncover important functions for Ihh signaling in controlling proliferation, differentiation, malignant progression, and metastasis of epithelial cancer, establishing Ihh as a gatekeeper for controlling the grade of tumor malignancy.

The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.

Science.gov (United States)

Campione, Elena; Paternò, Evelin Jasmine; Candi, Eleonora; Falconi, Mattia; Costanza, Gaetana; Diluvio, Laura; Terrinoni, Alessandro; Bianchi, Luca; Orlandi, Augusto

2015-01-01

Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclo-oxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action of PXM on the pathogenesis of nonmelanoma skin cancer, analyzing and evaluating binding modes and energies between COX-1 or COX-2 and PXM by protein-ligand molecular docking. Our clinical experience about the local use of PXM on actinic keratoses and field cancerization is also reported, confirming its efficacy as target therapy.

Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

DEFF Research Database (Denmark)

Corsino, P.; Davis, B.; Law, M.

2007-01-01

) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. Cell lines isolated from MMTV-cyclin D1-Cdk2 (MMTV-D1K2) tumors exhibit Rb and p130 hyperphosphorylation and up-regulation of the protein products of E2F-dependent genes. These results suggest that cyclin D1/Cdk2 complexes may...... sites. Together, these results suggest that deregulation of the Cdk/Rb/E2F axis reprograms mammary epithelial cells to initiate a paracrine loop with tumor-associated fibroblasts involving TGF beta and HGF, resulting in desmoplasia. The MMTV-DIK2 mice should provide a useful model system...

Gender affects skin wound healing in plasminogen deficient mice

DEFF Research Database (Denmark)

Rønø, Birgitte; Engelholm, Lars Henning; Lund, Leif Røge

2013-01-01

closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds...... functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency...... or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation...

Regulation of p53, nuclear factor κB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin

International Nuclear Information System (INIS)

Kalra, Neetu; Bhui, Kulpreet; Roy, Preeti; Srivastava, Smita; George, Jasmine; Prasad, Sahdeo; Shukla, Yogeshwer

2008-01-01

Bromelain is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas cosmosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties. In the present study, antitumorigenic activity of bromelain was recorded in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted 2-stage mouse skin model. Results showed that bromelain application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumors/mouse. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in antiapoptotic protein Bcl-2 in mouse skin. Since persistent induction of cyclooxygenase-2 (Cox-2) is frequently implicated in tumorigenesis and is regulated by nuclear factor-kappa B (NF-κB), we also investigated the effect of bromelain on Cox-2 and NF-κB expression. Results showed that bromelain application significantly inhibited Cox-2 and inactivated NF-κB by blocking phosphorylation and subsequent degradation of IκBα. In addition, bromelain treatment attenuated DMBA-TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), mitogen-activated protein kinase (MAPK) and Akt. Taken together, we conclude that bromelain induces apoptosis-related proteins along with inhibition of NF-κB-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced mouse skin tumors, which may account for its anti-tumorigenic effects

Inhibition of Akt enhances the chemopreventive effects of topical rapamycin in mouse skin

Science.gov (United States)

Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

2016-01-01

The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

Directory of Open Access Journals (Sweden)

Ines Herrmann

2010-10-01

Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

Risk reduction for nonmelanoma skin cancer with childhood sunscreen use

International Nuclear Information System (INIS)

Stern, R.S.; Weinstein, M.C.; Baker, S.G.

1986-01-01

Exposure to ultraviolet radiation is the principle cause of basal and squamous cell carcinomas of the skin, which are the most frequent tumors occurring in white residents of the United States. Using a mathematical model based on epidemiologic data, we quantified the potential benefits of using a sunscreen with a sun protective factor of 15 and estimate that regular use of such a sunscreen during the first 18 years of life would reduce the lifetime incidence of these tumors by 78%. Additional benefits of sunscreen use during childhood include reduced risk of sunburn, retarding the pace of skin aging, and possible reduction in melanoma risk. We recommend that pediatricians encourage sunscreen use and sun avoidance as a regular part of pediatric preventive health care

Near-infrared light activation of quenched liposomal Ce6 for synergistic cancer phototherapy with effective skin protection.

Science.gov (United States)

Feng, Liangzhu; Tao, Danlei; Dong, Ziliang; Chen, Qian; Chao, Yu; Liu, Zhuang; Chen, Meiwan

2017-05-01

Current photodynamic therapy (PDT) is suffering from limited efficacy towards hypoxia tumors and severe post-treatment photo-toxicity such as light-induced skin damages. To make PDT more effective in cancer treatment while being patient-comfortable, herein, a hexylamine conjugated chlorin e6 (hCe6) as the photosensitizer together with a lipophilic near-infrared (NIR) dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) are co-encapsulated into polyethylene glycol (PEG) shelled liposomes. In the obtained DiR-hCe6-liposome, the photosensitizing effect of hCe6 is quenched by DiR via fluorescence resonance energy transfer (FRET). Interestingly, upon irradiation with a 785-nm NIR laser to photobleach DiR, both fluorescence and photodynamic effect of hCe6 in DiR-hCe6-liposome would be activated. Meanwhile, such NIR irradiation applied on tumors of mice with intravenous injection of DiR-hCe6-liposome could result in mild photothermal heating, which in turn would promote intra-tumor blood flow and relieve tumor hypoxia, contributing to the enhanced photodynamic tumor treatment. Importantly, compared to hCe6-loaded liposomes, DiR-hCe6-liposome without being activated by the 785-nm laser shows much lower skin photo-toxicity, demonstrating its great skin protection effect. This work demonstrates a promising yet simple strategy to prepare NIR-light-activatable photodynamic theranostics for synergistic cancer phototherapy, which is featured high specificity/efficacy in tumor treatment with minimal photo-toxicity towards the skin. Copyright © 2016. Published by Elsevier Ltd.

Comparison of skin decontamination efficacy of commercial decontamination products following exposure to VX on human skin.

Science.gov (United States)

Thors, L; Koch, M; Wigenstam, E; Koch, B; Hägglund, L; Bucht, A

2017-08-01

The decontamination efficacy of four commercially available skin decontamination products following exposure to the nerve agent VX was evaluated in vitro utilizing a diffusion cell and dermatomed human skin. The products included were Reactive Skin Decontamination Lotion (RSDL), the Swedish decontamination powder 104 (PS104), the absorbent Fuller's Earth and the aqueous solution alldecontMED. In addition, various decontamination procedures were assessed to further investigate important mechanisms involved in the specific products, e.g. decontamination removal from skin, physical removal by sponge swabbing and activation of degradation mechanisms. The efficacy of each decontamination product was evaluated 5 or 30 min after dermal application of VX (neat or diluted to 20% in water). The RSDL-lotion was superior in reducing the penetration of VX through human skin, both when exposed as neat agent and when diluted to 20% in water. Swabbing with the RSDL-sponge during 2 min revealed decreased efficacy compared to applying the RSDL-lotion directly on the skin for 30 min. Decontamination with Fuller's Earth and alldecontMED significantly reduced the penetration of neat concentration of VX through human skin. PS104-powder was insufficient for decontamination of VX at both time-points, independently of the skin contact time of PS104. The PS104-slurry (a mixture of PS104-powder and water), slightly improved the decontamination efficacy. Comparing the time-points for initiated decontamination revealed less penetrated VX for RSDL and Fuller's Earth when decontamination was initiated after 5 min compared to 30 min post-exposure, while alldecontMED displayed similar efficacy at both time-points. Decontamination by washing with water only resulted in a significant reduction of penetrated VX when washing was performed 5 min after exposure, but not when decontamination was delayed to 30 min post-exposure of neat VX. In conclusion, early initiated decontamination with the

Biological effects of brachytherapy using a 32P-patch on the skin of Sencar mice

International Nuclear Information System (INIS)

Salgueiro, Maria J.; Medina, Vanina; Zubillaga, Marcela

2008-01-01

In recent years, specially designed patches containing beta emitters have been developed for contact brachytherapy of skin lesions. The aim of the present work is to evaluate the biological effects of the 32 P-patch on the skin of Sencar mice as a result of a brachytherapy treatment. For this purpose, a 32 P-patch was prepared with Chromic 32 P-phosphate and silicone and the classical model of two-stage skin carcinogenesis was reproduced in Sencar mice. Animals were divided in two main groups in order to perform the contact brachytherapy treatment using schemes of single (SD40 and SD60) and fractionated (FD40 and FD60) doses, with their respective control groups (CSD and CFD). Additionally, a control group without carcinogenic treatment was included in order to apply the 32 P-patch in normal skin. The endpoint to evaluate treatment effects was tumor size after a follow-up period of 44 days and finally, animals were sacrificed in order to get samples of all tumors for histological analysis. Additionally, PCNA staining was evaluated in all groups and the biologically effective dose (BED) of each scheme was calculated taken into account the linear-quadratic model. Erythema, dermatitis and skin ulceration developed in almost all treated animals, but they gradually healed with regeneration of tissue during the follow-up period. Radiation effects on the skin of SD40, SD60, FD40 and FD60 showed a significant reduction of the tumor size with regard to controls, independently of the scheme and the radiation dose considered. PCNA staining scores of groups in the single dose scheme resulted higher for control than for treated tumors, and the same pattern was observed for groups of the fractionated dose scheme. This radioactive 32 P-silicone-patch which, is easy to prepare and use in the treatment of skin diseases and seems promissory as a radioactive device for clinical use. (author)

Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

International Nuclear Information System (INIS)

Siddens, Lisbeth K.; Larkin, Andrew; Krueger, Sharon K.; Bradfield, Christopher A.; Waters, Katrina M.; Tilton, Susan C.; Pereira, Cliff B.; Löhr, Christiane V.; Arlt, Volker M.; Phillips, David H.; Williams, David E.

2012-01-01

The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by 32 P post‐labeling, did not correlate with tumor incidence. PAH‐dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p < 0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique pattern of

Basal cell carcinoma arising on the skin with chronic radiation dermatitis

International Nuclear Information System (INIS)

Tanaka, Yukiko; Ogusa, Yasuhiro; Tamura, Shinya

1986-01-01

In a 86-year-old woman, basal cell carcinoma (BCC) arose on the skin with chronic radiation dermatitis. She, at the age of 46, received irradiation to the abdomen for cancer of the uterine cervix. Radiation source and dose were unknown. A verrucous eruption appeared on the irradiated field of the right abdomen, and gradually expanded. Histological examination showed that proliferation of tumor cells with adenoid and cystose structure extended to the epidermis. Electron microscopic study showed both clear and dark tumor cells, although dark cells were few in number. A review of the literature showed that BCC arising on the skin with chronic radiation dermatitis is uncommon in Japan. (Namekawa, K.)

Autofluorescence of pigmented skin lesions using a pulsed UV laser with synchronized detection: clinical results

Science.gov (United States)

Cheng, Haynes P. H.; Svenmarker, Pontus; Xie, Haiyan; Tidemand-Lichtenberg, Peter; Jensen, Ole B.; Bendsoe, Niels; Svanberg, Katarina; Petersen, Paul Michael; Pedersen, Christian; Andersson-Engels, Stefan; Andersen, Peter E.

2010-04-01

We report preliminary clinical results of autofluorescence imaging of malignant and benign skin lesions, using pulsed 355 nm laser excitation with synchronized detection. The novel synchronized detection system allows high signal-tonoise ratio to be achieved in the resulting autofluorescence signal, which may in turn produce high contrast images that improve diagnosis, even in the presence of ambient room light. The synchronized set-up utilizes a compact, diode pumped, pulsed UV laser at 355 nm which is coupled to a CCD camera and a liquid crystal tunable filter. The excitation and image capture is sampled at 5 kHz and the resulting autofluorescence is captured with the liquid crystal filter cycling through seven wavelengths between 420 nm and 580 nm. The clinical study targets pigmented skin lesions and evaluates the prospects of using autofluorescence as a possible means in differentiating malignant and benign skin tumors. Up to now, sixteen patients have participated in the clinical study. The autofluorescence images, averaged over the exposure time of one second, will be presented along with histopathological results. Initial survey of the images show good contrast and diagnostic results show promising agreement based on the histopathological results.

Percutaneous Renal Tumor Ablation: Radiation Exposure During Cryoablation and Radiofrequency Ablation

Energy Technology Data Exchange (ETDEWEB)

McEachen, James C., E-mail: james.mceachen2@gmail.com [Mayo Clinic, Division of Preventive, Occupational, and Aerospace Medicine (United States); Leng, Shuai; Atwell, Thomas D. [Mayo Clinic, Department of Radiology (United States); Tollefson, Matthew K. [Mayo Clinic, Department of Urology (United States); Friese, Jeremy L. [Mayo Clinic, Department of Radiology (United States); Wang, Zhen; Murad, M. Hassan [Mayo Clinic, Division of Preventive, Occupational, and Aerospace Medicine (United States); Schmit, Grant D. [Mayo Clinic, Department of Radiology (United States)

2016-02-15

IntroductionOnce reserved solely for non-surgical cases, percutaneous ablation is becoming an increasingly popular treatment option for a wider array of patients with small renal masses and the radiation risk needs to be better defined as this transition continues.Materials and MethodsRetrospective review of our renal tumor ablation database revealed 425 patients who underwent percutaneous ablation for treatment of 455 renal tumors over a 5-year time period. Imparted radiation dose information was reviewed for each procedure and converted to effective patient dose and skin dose using established techniques. Statistical analysis was performed with each ablative technique.ResultsFor the 331 cryoablation procedures, the mean DLP was 6987 mGycm (SD = 2861) resulting in a mean effective dose of 104.7 mSv (SD = 43.5) and the mean CTDI{sub vol} was 558 mGy (SD = 439) resulting in a mean skin dose of 563.2 mGy (SD = 344.1). For the 124 RFA procedures, the mean DLP was 3485 mGycm (SD = 1630) resulting in a mean effective dose of 50.3 mSv (SD = 24.0) and the mean CTDI{sub vol} was 232 mGy (SD = 149) resulting in a mean skin dose of 233.2 mGy (SD = 117.4). The difference in patient radiation exposure between the two renal ablation techniques was statistically significant (p < 0.001).ConclusionBoth cryoablation and RFA imparted an average skin dose that was well below the 2 Gy deterministic threshold for appreciable sequela. Renal tumor cryoablation resulted in a mean skin and effective radiation dose more than twice that for RFA. The radiation exposure for both renal tumor ablation techniques was at the high end of the medical imaging radiation dose spectrum.

Study of mast cell count in skin tags

Directory of Open Access Journals (Sweden)

Zaher Hesham

2007-01-01

Full Text Available Background: Skin tags or acrochordons are common tumors of middle-aged and elderly subjects. They consist of loose fibrous tissue and occur mainly on the neck and major flexures as small, soft, pedunculated protrusions. Objectives: The aim was to compare the mast cells count in skin tags to adjacent normal skin in diabetic and nondiabetic participants in an attempt to elucidate the possible role of mast cells in the pathogenesis of skin tags. Participants and Methods: Thirty participants with skin tags were divided into group I (15 nondiabetic participants and group II (15 diabetic participants. Three biopsies were obtained from each participant: a large skin tag, a small skin tag and adjacent normal skin. Mast cell count from all the obtained sections was carried out, and the mast cell density was expressed as the average mast cell count/high power field (HPF. Results: A statistically significant increase in mast cells count in skin tags in comparison to normal skin was detected in group I and group II. There was no statistically significant difference between mast cell counts in skin tags of both the groups. Conclusion: Both the mast cell mediators and hyperinsulinemia are capable of inducing fibroblast proliferation and epidermal hyperplasia that are the main pathologic abnormalities seen in all types of skin tags. However, the presence of mast cells in all examined skin tags regardless of diabetes and obesity may point to the possible crucial role of mast cells in the etiogenesis of skin tags through its interaction with fibroblasts and keratinocytes.

Ocular melanoma metastatic to skin: the value of HMB-45 staining.

Science.gov (United States)

Schwartz, Robert A; Kist, Joseph M; Thomas, Isabelle; Fernández, Geover; Cruz, Manuel A; Koziorynska, Ewa I; Lambert, W Clark

2004-06-01

Cutaneous metastatic disease is an important finding that may represent the first sign of systemic cancer, or, if already known, that may change tumor staging and thus dramatically altered therapeutic plans. Although cutaneous metastases are relatively frequent in patients with cutaneous melanoma, they are less so from ocular melanoma. To demonstrate the value of HMB-45, staining in the detection of ocular melanoma metastatic to skin. The immunohistochemical stain HMB-45 a monoclonal antibody directed against intact human melanoma cells, was employed on a skin biopsy specimen from a cutaneous tumor. HMB-45 staining was positive in the atypical hyperchromatic cells of the deep dermis. HMB-45 may be of value in the detection of ocular melanoma metastatic to skin. Cutaneous metastatic disease is a somewhat common and extremely important diagnosis. Although cutaneous metastases from cutaneous melanoma are relatively frequent, those from ocular melanomas are less so. Use of histochemical staining, especially the HMB-45 stain, allows confirmation of the diagnosis.

Precancerous Skin Lesions.

Science.gov (United States)

Ferrándiz, C; Malvehy, J; Guillén, C; Ferrándiz-Pulido, C; Fernández-Figueras, M

Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin.

Science.gov (United States)

Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X

2006-01-12

Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.

Tumor immunology

International Nuclear Information System (INIS)

Otter, W. den

1987-01-01

Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis

Science.gov (United States)

Putz, Eva M.; Guillerey, Camille; Kos, Kevin; Stannard, Kimberley; Miles, Kim; Delconte, Rebecca B.; Nicholson, Sandra E.; Huntington, Nicholas D.; Smyth, Mark J.

2017-01-01

ABSTRACT The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy. PMID:28344878

Anti-tumor activity of tetrodotoxin extracted from the Masked Puffer ...

African Journals Online (AJOL)

Anti-tumor activity of tetrodotoxins extracted from the skin of the Masked Puffer fish (Arothron diadematus) from the Red Sea was evaluated using the Ehrlich ascite carcinoma tumor model in mice. Activity was assessed using a variety of cellular and liver biochemical parameters. Experimental mice were divided into 4 equal ...

Caffeine decreases phospho-Chk1 (Ser317) and increases mitotic cells with cyclin B1 and caspase 3 in tumors from UVB-treated mice.

Science.gov (United States)

Lu, Yao-Ping; Lou, You-Rong; Peng, Qing-Yun; Nghiem, Paul; Conney, Allan H

2011-07-01

Oral administration of caffeine to mice inhibits UVB-induced carcinogenesis, and these results are paralleled by epidemiology studies indicating that caffeinated coffee and tea intake (but not decaffeinated beverage intake) is associated with decreased incidence of nonmelanoma skin cancer. Topical applications of caffeine to the skin of SKH-1 mice that had previously been treated with UVB inhibited subsequent skin tumor development and stimulated apoptosis in tumors but not in nontumor areas of the epidermis. This study sought to determine the basis of these differential effects on tumor versus nontumor sites that can be induced by caffeine, long after all UVB treatment has ceased. The activation status of the ATR/Chk1 pathway in UVB-induced tumors and uninvolved skin was determined by quantitating phospho-Chk1 (Ser317) and induction of lethal mitosis in vivo in the presence and absence of topical caffeine treatment. In the absence of caffeine, we found that UVB-induced tumors often had islands of phospho-Chk1 (Ser317) staining cells that were not present in nontumor areas of the epidermis. Treatment of mice with topical caffeine significantly diminished phospho-Chk1 (Ser317) staining and increased the number of mitotic cells that expressed cyclin B1 and caspase 3 in tumors, consistent with caffeine-induced lethal mitosis selectively in tumors. We hypothesize that compared with adjacent uninvolved skin, UVB-induced skin tumors have elevated activation of, and dependence on, the ATR/Chk1 pathway long after UVB exposure has ceased and that caffeine can induce apoptosis selectively in tumors by inhibiting this pathway and promoting lethal mitosis.

The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil

Directory of Open Access Journals (Sweden)

Youssef W. Naguib

2014-02-01

Full Text Available Topical 5-fluorouracil (5-FU is approved for the treatment of superficial basal cell carcinoma and actinic keratosis. However, 5-FU suffers from poor skin permeation. Microneedles have been successfully applied to improve the skin permeability of small and large molecules, and even nanoparticles, by creating micron-sized pores in the stratum corneum layer of the skin. In this report, the feasibility of using microneedles to increase the skin permeability of 5-FU was tested. Using full thickness mouse skin mounted on Franz diffusion apparatus, it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles (500 μm in length, 50 μm in base diameter. In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space, the antitumor activity of a commercially available 5-FU topical cream (5% was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles, as compared to when the cream was simply applied on a skin area, underneath which the tumor cells were implanted, and without pretreatment of the skin with microneedles. Fluorouracil is not approved for melanoma therapy, but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.

Upregulation of mitochondrial NAD+ levels impairs the clonogenicity of SSEA1+ glioblastoma tumor-initiating cells.

Science.gov (United States)

Son, Myung Jin; Ryu, Jae-Sung; Kim, Jae Yun; Kwon, Youjeong; Chung, Kyung-Sook; Mun, Seon Ju; Cho, Yee Sook

2017-06-09

Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD + ) metabolism. However, the functional role of NAD + metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD + levels affect the characteristics of glioma-driven SSEA1 + TICs, including clonogenic growth potential. An increase in the mitochondrial NAD + levels by the overexpression of the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) significantly suppressed the sphere-forming ability and induced differentiation of TICs, suggesting a loss of the characteristics of TICs. In addition, increased SIRT3 activity and reduced lactate production, which are mainly observed in healthy and young cells, appeared following NNT-overexpressed TICs. Moreover, in vivo tumorigenic potential was substantially abolished by NNT overexpression. Conversely, the short interfering RNA-mediated knockdown of NNT facilitated the maintenance of TIC characteristics, as evidenced by the increased numbers of large tumor spheres and in vivo tumorigenic potential. Our results demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD + levels and SIRT3 activity could be a promising strategy for abolishing the development of TICs as a new therapeutic approach to treating aging-associated tumors.

Combination chemoprevention with diclofenac, calcipotriol and difluoromethylornithine inhibits development of non-melanoma skin cancer in mice

DEFF Research Database (Denmark)

Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob

2013-01-01

Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model.......Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model....

Radiation-induced vascular lesions of the skin: an overview

NARCIS (Netherlands)

Flucke, U.E.; Requena, L.; Mentzel, T.

2013-01-01

Radiation-induced cutaneous vascular neoplasms occur infrequently and comprise benign, so-called atypical vascular lesions (AVL) and angiosarcomas (AS), often being high-grade malignant tumors. Both arise most frequently within previously irradiated skin in breast-conserving-treated mammary cancer

Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

Directory of Open Access Journals (Sweden)

Kristine von Maltzan

2016-02-01

Full Text Available The Slug transcription factor plays an important role in ultraviolet radiation (UVR-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2 pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.

Mobile phone use and the risk of skin cancer

DEFF Research Database (Denmark)

Poulsen, Aslak Harbo; Friis, Søren; Johansen, Christoffer

2013-01-01

The International Agency for Research on Cancer has classified radiofrequency radiation as possibly carcinogenic. Previous studies have focused on intracranial tumors, although the skin receives much radiation. In a nationwide cohort study, 355,701 private mobile phone subscribers in Denmark from......% confidence interval: 0.54, 2.00). A similar risk pattern was seen among women, though it was based on smaller numbers. In this large, population-based cohort study, little evidence of an increased skin cancer risk was observed among mobile phone users....

Reduction mammaplasty and radiation therapy can allow breast conservation in patients with breast cancers not initially treatable by tumor-ectomy

International Nuclear Information System (INIS)

Otmezguine, Y.; Calitchi, E.; Cothier, I.; Feuilhade, F.; Le Bourgeois, J.P.; Baruch, J.

1997-01-01

A protocol combining reduction mammaplasty (RM) and radiation therapy was developed as an alternative of mastectomy in patients with breast cancers larger than 3 cm in diameter. This protocol was used in 51 patients between 1983 and 1990. Indications were extensive microcalcifications (n = 17; 33 %) ; residual tumor after neo-adjuvant therapy larger than 4 cm in diameter (n 18 ; 35 %); extensive DCIS (n = 4; 8 %) or tumor located within an area of fibrocystic disease (n = 6; 12 %); presence of a bifocal lesion (n = 12 %. area of fibrocystic disease (n = 6; 12 %); and presence of bifocal lesion (n 6; 12 %). Surgery consisted of tumor-ectomy removing a wide margin of skin and mammary gland, followed by immediate remodeling of the breast, same-side axillary node clearance, and symmetrization of the other breast. A radiation dose of 45 Gy was delivered to the entire mammary gland. Adjuvant therapy was given before and/or after therapy according to the institution's routine breast cancer protocol. During the mean follow-up of 8.1 years, four patients (8 %) developed a local recurrence, which has treated surgically. The five-year disease-free survival rate was 76 %. The cosmetic result was good or very good in 78% of cases. RM plus RT is a reasonable alternative to mastectomy in patients with large breast cancers, although further work is needed to refine its indications. (authors)

Ultraviolet radiation, cancer of the skin and immunology

International Nuclear Information System (INIS)

Suurmond, D.

1984-01-01

The effects of near and far ultraviolet radiation on the development of skin neoplasms are reviewed. Especially the role of ultraviolet radiation in immunosuppression is discussed as a possible working mechanism of the tumor promoting the effect of this radiation, beside effects on DNA-repair. (Auth.)

A case of desmoplastic melanoma that was difficult to distinguish from malignant peripheral nerve sheath tumor

Directory of Open Access Journals (Sweden)

Kenji Yorita

2018-03-01

Full Text Available The clinical and pathological diagnosis of desmoplastic melanoma is difficult, because almost 50% of desmoplastic melanoma cases involve non-pigmented lesions and the tumor cells can resemble fibroblasts or Schwannian cells based on their frequent amelanotic features. Moreover, desmoplastic melanoma typically has low positive rates for melanoma markers, with the exception of the S-100 protein. We report the case of an 81-year-old Japanese man with an 8-mm desmoplastic melanoma. He initially noticed a painless and non-pigmented skin lesion that did not grow noticeably for 6 months. It was unlikely that he had von Recklinghausen disease, and the mass was initially considered a dermatofibroma. Excisional biopsy revealed an intradermal mass, with the superficial portion mimicking neurofibroma and the deeper portion exhibiting nodular growth of sarcomatoid spindle cells. The tumor region lacked intradermal proliferation of atypical melanocytic cells, intracytoplasmic melanin, and expression of melanoma markers (except S-100 protein and Sox10. Although a malignant peripheral nerve sheath tumor derived from neurofibroma was possible, the slow growth with diffuse and strong immunoreactivity to the S-100 protein and Sox10 favored a diagnosis of desmoplastic melanoma. Pathologists should recognize that desmoplastic melanoma may not involve in situ lesions or the immunohistochemical expression of standard melanoma markers.

Bilateral Wilms' tumor with anaplasia: lessons from the National Wilms' Tumor Study.

Science.gov (United States)

Hamilton, Thomas E; Green, Daniel M; Perlman, Elizabeth J; Argani, Pedram; Grundy, Paul; Ritchey, Michael L; Shamberger, Robert C

2006-10-01

The purpose of this study was to evaluate whether initial diagnostic technique influenced the ability to identify anaplastic histology, to determine the time interval to diagnosis of anaplasia, and to delineate the incidence of discordant pathology in bilateral Wilms' tumor. We hypothesized that delay in diagnosis of anaplasia could affect time to appropriate surgery and intensive multimodality therapy. One hundred eight-nine children were enrolled in the fourth National Wilms' Tumor Study with synchronous bilateral tumors, 27 of whom were eventually shown to have anaplastic histology. Initial diagnostic technique, time interval to diagnosis of anaplasia, and the incidence of discordant pathology were determined. Anaplasia was identified in 0 of 7 tumors by core needle biopsy, 3 of 9 tumors by open wedge biopsy, and in 7 of 9 cases by partial or complete nephrectomy. The mean duration of first chemotherapy regimen (DD or EE) was 20, 39, and 36 weeks, respectively, before anaplasia was identified at second surgery. Discordant pathology between bilateral tumors was identified on final tissue diagnosis in 20 patients. Only 4 patients had anaplastic tumors in both kidneys. Core needle biopsy did not identify anaplasia in 7 of 7 children. Open biopsy or partial/complete nephrectomy identified anaplasia at initial diagnostic procedure in 10 of 18 children. Twenty of 24 patients at final tissue diagnosis had discordant pathology between the 2 kidneys. Earlier interval incisional biopsy or resection may identify anaplastic histology and limit the duration of chemotherapy targeted to favorable histology for children with bilateral Wilms' tumor and anaplasia.

Imaging Blood Vessel Morphology in Skin

DEFF Research Database (Denmark)

Schuh, Sandra; Holmes, Jon; Ulrich, Martina

2017-01-01

Conventional optical coherence tomography (OCT) enables the visualization of morphological changes of skin cancer. The use of OCT in the diagnostic investigation and in the therapy decision of non-melanoma skin cancer and other skin changes is already established, and has found its way into routine...... practice. With the development of speckle-variance OCT, also named dynamic OCT (D-OCT), the vascular architecture and the blood flow of the skin can be displayed in vivo and in 3D. This novel angiographic variant of OCT offers the ability to visualize and measure vessel morphology providing a new insight...... into healthy, inflammatory and neoplastic skin lesions such as malignant melanoma. This review focuses on the possibilities of using D-OCT on healthy and diseased skin. We suggest and illustrate key diagnostic characteristics by analyzing the initial publications and preliminary unpublished data on vessel...

A comprehensive evaluation of the mechanism of skin tumorigenesis by straight-run and cracked petroleum middle distillates.

Science.gov (United States)

Nessel, C S; Priston, R A; McKee, R H; Cruzan, G; Riley, A J; Hagemann, R; Plutnick, R T; Simpson, B J

1998-07-01

The role of skin irritation and other factors on the tumorigenic activity of petroleum middle distillates (PMDs) in mice was examined in a comprehensive research program. The program culminated in a 2-year dermal carcinogenicity study which compared the effects of equal weekly doses of irritating and nonirritating PMDs. Modified Ames mutagenicity studies and three- to seven-ring polycyclic aromatic compound (PAC) analyses indicated that the mutagenic activity of PMDs was correlated to PAC content. In subchronic and subacute studies, PMDs produced marked skin irritation which was ameliorated if the test samples were diluted in mineral oil. The reduction in irritation level was not a result of reduced dermal absorption. Straight-run kerosine (SRK), straight-run gas oil (SRGO), and catalytically cracked light cycle oil (LCO) were evaluated in the dermal carcinogenicity study. Test materials were applied either undiluted (2x/week) or as 28.5% (7x/week) or 50% (4x/week) concentrations in mineral oil for a total weekly dose of 100 microliters PMD per animal. All three materials produced moderate to marked skin irritation and increased tumor frequency when applied undiluted. When diluted, the irritant effects of SRK and SRGO, which contain low levels of PACs, were ameliorated, and there were no significant increases in tumors relative to controls. LCO, containing 8.7% three- to seven-ring PACs, increased tumor frequency when diluted, even when skin irritation was limited. These data indicate that the tumorigenic activity of straight-run MDs is likely a consequence of a nongenotoxic process, associated with frequent cell damage and repair. PMDs which contain low levels of three- to seven-ring PACs are unlikely to cause tumors in the absence of prolonged skin irritation. In addition, genotoxic mechanisms may also contribute to tumor formation for other PMDs containing higher levels of PACs, e.g., products blended with cracked stocks.

Clinico-roentgenological semiotics of malignant contact bone tumors

International Nuclear Information System (INIS)

Akperbekov, A.A.; Polatkhanova, K.B.; Murtuzaeva, Z.D.

1986-01-01

Bone changes were analyzed in 42 patients (aged 18 to 65) with malignant contact bone tumors. Probable causes of their origin were discussed. Of 42 patients corticopleural cancer (Pancoast's tumor) was noted in 24, skin cancer developing against a background of a chronic inflammatory process or trauma, was noted in 13, sarcomatous soft tissue tumors in 5. A method of roentgenography using routine and spot radiographs was used for X-ray examination of the patients. In some cases the examination was supplemented with hard and soft X-ray films, tomography and electroroentgenography

Percutaneous fiducial marker placement prior to stereotactic body radiotherapy for malignant liver tumors: an initial experience

International Nuclear Information System (INIS)

Ohta, Kengo; Shimohira, Masashi; Murai, Taro; Nishimura, Junichi; Iwata, Hiromitsu; Ogino, Hiroyuki; Hashizume, Takuya; Shibamoto, Yuta

2016-01-01

The aim of this study was to describe our initial experience with a gold flexible linear fiducial marker and to evaluate the safety and technical and clinical efficacy of stereotactic body radiotherapy using this marker for malignant liver tumors. Between July 2012 and February 2015, 18 patients underwent percutaneous fiducial marker placement before stereotactic body radiotherapy for malignant liver tumors. We evaluated the technical and clinical success rates of the procedure and the associated complications. Technical success was defined as successful placement of the fiducial marker at the target site, and clinical success was defined as the completion of stereotactic body radiotherapy without the marker dropping out of position. All 18 fiducial markers were placed successfully, so the technical success rate was 100% (18/18). All 18 patients were able to undergo stereotactic body radiotherapy without marker migration. Thus, the clinical success rate was 100% (18/18). Slight pneumothorax occurred as a minor complication in one case. No major complications such as coil migration or bleeding were observed. The examined percutaneous fiducial marker was safely placed in the liver and appeared to be useful for stereotactic body radiotherapy for malignant liver tumors

The incidence of skin cancer in Nagasaki atomic bomb survivors, 1955 - 1984

International Nuclear Information System (INIS)

Sadamori, Naoki; Mine, Mariko; Hori, Makoto; Yoshida, Hikotaro; Ichimaru, Michito; Honda, Takeo; Yoshida, Katsuro; Fujiwara, Naoko; Sadamori, Michiko.

1988-01-01

Of 20,348 persons included in the extended Life Span Study in Nagasaki, 59 persons were registered as having skin tumors during the years 1955 - 1984. Included in this study were 40 patients with histologically proven skin cancer. Thirty five patients were considered to be exposed to ≥ one cGy. There was statistically significant correlation between the incidence of skin cancer and exposure doses in both men and women (p < 0.01). Overall, the incidence of skin cancer was significantly correlated as well with the distance from the hypocenter; however, this was not significant when restricted to either men or women. Because the incidence of skin cancer has definitively increased since 1955 among A-bomb survivors, follow-up of A-bomb survivors is warranted with respect to atomic bomb-related skin cancer. (Namekawa, K.)

Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.

Science.gov (United States)

Ye, Xuying; Yin, Huijuan; Lu, Yu; Zhang, Haixia; Wang, Han

2016-10-12

We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

Detection of human papillomavirus in nonmelanoma skin cancer lesions and healthy perilesional skin in kidney transplant recipients and immunocompetent patients.

Science.gov (United States)

Bernat-García, J; Morales Suárez-Varela, M; Vilata-Corell, J J; Marquina-Vila, A

2014-04-01

The influence of human papillomavirus (HPV) on the development of nonmelanoma skin cancer (NMSC) is a topic of debate. HPV types from the beta genus (HPV-β) have been most frequently associated with the development of skin cancer. To analyze the prevalence and range of HPV types in NMSC lesions and healthy perilesional skin in immunodepressed and immunocompetent patients and to evaluate the influence of various clinical factors on the prevalence of HPV in skin cancer. Nested polymerase chain reaction and sequencing were used to detect HPV in 120 NMSC samples obtained by biopsy from 30 kidney transplant recipients and 30 immunocompetent patients. In all cases, a sample was taken from the tumor site and the surrounding healthy skin. Potential confounders were assessed and the data analyzed by multivariate logistic regression. HPV DNA was detected in 44 (73.3%) of the 60 samples from immunodepressed patients and in 32 (53.3%) of the 60 samples from immunocompetent patients (adjusted odds ratio, 3.4; 95% CI, 1.2-9.6). In both groups of patients, HPV was more common in healthy perilesional skin than in lesional skin. HPV-β was the most common type isolated. We found a wide range of HPV types (mostly HPV-β) in the skin of kidney transplant recipients and immunocompetent patients with skin cancer. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

Harnessing dendritic cells in inflammatory skin diseases.

Science.gov (United States)

Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

2011-02-01

The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Childhood malignant blue nevus of the ear associated with two intracranial melanocytic tumors-metastases or neurocutaneous melanosis?

Science.gov (United States)

Popović, Mara; Dolenc-Strazar, Zvezdana; Anzic, Jozica; Luzar, Bostjan

2004-10-01

Blue nevus is an uncommon pigmented tumor of dermal melanocytes that has traditionally been classified into common and cellular variant. It is usually a skin tumor in adults but can become apparent in early childhood or even be present at birth. Malignant blue nevus is a rare melanocytic tumor of the skin arising from a preexisting cellular blue nevus. We report a multinodular blue nevus of the left ear in an 11-year-old girl who also had 2 intracranial melanocytic lesions. Differential diagnosis between metastases from malignant blue nevus and neurocutaneous melanosis is discussed.

Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells.

Science.gov (United States)

Brown, Christine E; Starr, Renate; Aguilar, Brenda; Shami, Andrew F; Martinez, Catalina; D'Apuzzo, Massimo; Barish, Michael E; Forman, Stephen J; Jensen, Michael C

2012-04-15

To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to target this therapeutically resistant glioma subpopulation. A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine(+) CTL-mediated killing in vitro and in vivo. We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2(pos) cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine(+) CTL were capable of efficient recognition and killing of both IL13Rα2(pos) GSCs and IL13Rα2(pos) differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine(+) CTL displayed robust antitumor activity against established IL13Rα2(pos) GSC TS-initiated orthotopic tumors in mice. Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine(+) CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations. ©2012 AACR.

Radiobiological parameters of a human tumor parent line and four tumor clones of a human epidermoid carcinoma

International Nuclear Information System (INIS)

Weichselbaum, R.R.; Beckett, M.; Dahlberg, W.

1987-01-01

The authors examined the radiobiological parameters of a parent tumor line and four tumor clones of a human squamous cell carcinoma of the skin. The parent line and clones have a tumor morphology, aneuploid karyotype, and the ability to passage continuously in vitro. With the exception of clone F2A, all cell lines form tumors in nude mice. The parent line, SCC-12 has a D/sub o/ of 154 and an n 7.5 In four tumor clones, D/sub o/ ranges from 131 (clone V) to 266 (clone B2); n ranges from 22.8 in clone V to 2.1 in clone B2. PLDR following 1100 rad ranges from 1.7 in clone B2 to 13.1 in clone V. However, PLDR following equitoxic doses of radiation is similar in the parent and all sub-clones. Radiobiological heterogeneity may complicate predictive assays for clinical radiotherapy

The contribution of skin blood flow in warming the skin after the application of local heat; the duality of the Pennes heat equation.

Science.gov (United States)

Petrofsky, Jerrold; Paluso, Dominic; Anderson, Devyn; Swan, Kristin; Yim, Jong Eun; Murugesan, Vengatesh; Chindam, Tirupathi; Goraksh, Neha; Alshammari, Faris; Lee, Haneul; Trivedi, Moxi; Hudlikar, Akshay N; Katrak, Vahishta

2011-04-01

As predicted by the Pennes equation, skin blood flow is a major contributor to the removal of heat from an external heat source. This protects the skin from erythema and burns. But, for a person in a thermally neutral room, the skin is normally much cooler than arterial blood. Therefore, if skin blood flow (BF) increases, it should initially warm the skin paradoxically. To examine this phenomenon, 10 young male and female subjects participated in a series of experiments to examine the contribution of skin blood flow in the initial warming the skin after the application of local heat. Heat flow was measured by the use of a thermode above the brachioradialis muscle. The thermode was warmed by constant temperature water at 44°C entering the thermode at a water flow rate of 100 cm(3)/min. Skin temperature was measured by a thermistor and blood flow in the underlying skin was measured by a laser Doppler imager in single point mode. The results of the experiments showed that, when skin temperature is cool (31-32°C), the number of calories being transferred to the skin from the thermode cannot account for the rise in skin temperature alone. A significant portion of the rise in skin temperature is due to the warm arterialized blood traversing the skin from the core areas of the body. However, as skin temperature approaches central core temperature, it becomes less of a heat source and more of a heat sync such that when skin temperature is at or above core temperature, the blood flow to the skin, as predicted by Pennes, becomes a heat sync pulling heat from the thermode. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients.

Science.gov (United States)

Borgogna, Cinzia; Lanfredini, Simone; Peretti, Alberto; De Andrea, Marco; Zavattaro, Elisa; Colombo, Enrico; Quaglia, Marco; Boldorini, Renzo; Miglio, Umberto; Doorbar, John; Bavinck, Jan N Bouwes; Quint, Koen D; de Koning, Maurits N C; Landolfo, Santo; Gariglio, Marisa

2014-08-01

The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.

Neuroendocrine tumors and smoking

Directory of Open Access Journals (Sweden)

Tanja Miličević

2016-12-01

Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

Optical coherence tomography for the diagnosis of malignant skin tumors: a meta-analysis

Science.gov (United States)

Xiong, Yi-Quan; Mo, Yun; Wen, Yu-Qi; Cheng, Ming-Ji; Huo, Shu-Ting; Chen, Xue-Jiao; Chen, Qing

2018-02-01

Optical coherence tomography (OCT) is an emergent imaging tool used for noninvasive diagnosis of skin diseases. The present meta-analysis was carried out to assess the accuracy of OCT for the diagnosis of skin cancer. We conducted a systematic literature search though EMBASE, Medline, PubMed, the Cochrane Library, and Web of Science database for relevant articles published up to June 6, 2017. The quality of the included studies was assessed using the QUADAS-2 tool and the Oxford Levels of Evidence Scale. Statistical analyses were conducted using the software Meta-Disc version 1.4 and STATA version 12.0. A total of 14 studies involving more than 813 patients with a total of 1958 lesions were included in our analyses. The pooled sensitivity and specificity of OCT for skin cancer diagnoses were 91.8% and 86.7%, respectively. Subgroup analysis showed that the pooled sensitivities of OCT for detecting basal cell carcinoma (BCC), squamous cell carcinoma (SCC), actinic keratosis, and malignant melanoma were 92.4%, 92.3%, 73.8%, and 81.0%, respectively. The pooled specificities were 86.9%, 99.5%, 91.5%, and 93.8%, respectively. OCT appears to be useful for the detection of BCC and SCC. It is a valuable diagnostic method when screening for early skin cancers.

Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin

DEFF Research Database (Denmark)

André, F M; Gehl, J; Sersa, G

2008-01-01

Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across the permeab......Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across...... the permeabilized membrane. To investigate this further, combinations of permeabilizing short high-voltage pulses (HV; hundreds of V/cm) and mainly electrophoretic long low-voltage pulses (LV; tens of V/cm) were investigated in muscle, liver, tumor, and skin in rodent models. The following observations were made......, but not to liver; and (4) efficient gene electrotransfer was achieved with HV field strengths below the detectability thresholds for permeabilization; and (5) the lag time interval between the HV and LV pulses decreased sensitivity to the HV pulses, enabling a wider HV amplitude range. In conclusion, HV plus LV...

Proliferating Trichilemmal Tumor of the Knee Mimicking Prepatellar Bursitis on Ultrasonogram: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Lee, Il Jin; Kim, Tae Eun; Lee, Il Gi; Shin, Hyeon Woong [Daegu Fatima Hospital, Daegu (Korea, Republic of)

2011-03-15

Proliferating trichilemmal tumor is a rare benign tumor of skin appendage. It is usually solitary, more common in women after the fourth decade of life, and almost exclusively confined to the scalp and back of the neck. We report herein an unusual case of proliferating trchilemmal tumor which occurred on the knee

Proliferating Trichilemmal Tumor of the Knee Mimicking Prepatellar Bursitis on Ultrasonogram: A Case Report

International Nuclear Information System (INIS)

Lee, Il Jin; Kim, Tae Eun; Lee, Il Gi; Shin, Hyeon Woong

2011-01-01

Proliferating trichilemmal tumor is a rare benign tumor of skin appendage. It is usually solitary, more common in women after the fourth decade of life, and almost exclusively confined to the scalp and back of the neck. We report herein an unusual case of proliferating trchilemmal tumor which occurred on the knee

Origin of malignant tumors of the upper respiratory and digestive tracts and the ear. Pt. 4. Malignant tumors caused by irradiation. B. Special part

Energy Technology Data Exchange (ETDEWEB)

Leicher, H [Mainz Univ. (Germany, F.R.). Hals-, Nasen- und Ohrenklinik

1979-12-01

The problem of radiation induced tumors is explained in detail in the following chapters: 1. Malignant tumors in dial painters using luminous paint, 2. Malignant tumors after injection of Thorotrast, 3. Bronchial tumors in Uran-mineworkers, 4. Malignant tumors caused by radium-compresses and radium-moulages, 5. Thyroid cancer caused by irradiation, 6. Leukemia and malignant tumors following the atomic bomb detonation in Hiroshima and Nakasaki, 7. Malignant tumors in Lupus vulgaris, 8. Development of malignant tumors following the irradiation of praecancerous alterations, of benign tumors and other benign changes in head and neck, 9. Radiation induced soft-tissue and bone sarcoma in the skull, 10. Radiation-induced cancers in hypopharynx diverticula, 11. Radiation-induced cancers in the antethoracic skin graft esophagus, 12. Radiation-induced second-tumors, 13. Cancer caused by ultraviolet rays, 14. Increase of hematogenic metastases by irradiation. 15. Malignant tumors caused by irradiation of the fetus in utero.

Skin Diseases: Skin Health and Skin Diseases

Science.gov (United States)

Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

Significant skin burns may occur with the use of a water balloon in HIFU treatment

Science.gov (United States)

Ritchie, Robert; Collin, Jamie; Wu, Feng; Coussios, Constantin; Leslie, Tom; Cranston, David

2012-10-01

HIFU is a minimally-invasive therapy suitable for treating selected intra-abdominal tumors. Treatment is safe although skin burns may occur due to pre-focal heating. HIFU treatment of a renal transplant tumor located in the left lower abdomen was undertaken in our centre. Treatment was performed prone, requiring displacement of the abdominal wall away from the treatment field using a water balloon, constructed of natural rubber latex and filled with degassed water. Intra-operatively, ultrasound imaging and physical examination of the skin directly over the focal region was normal. Immediately post-operative, a full-thickness skin burn was evident at the periphery of the balloon location, outside the expected HIFU path. Three possibilities may account for this complication. Firstly, the water balloon may have acted as a lens, focusing the HIFU to a neo-focus off axis. Secondly, air bubbles may have been entrapped between the balloon and the skin, causing heating at the interface. Finally, heating of the isolated water within the balloon may have been sufficient to cause burning. In this case, the placement of a water balloon caused a significant skin burn. Care should be taken in their use as burns, situated off axis, may occur even if the overlying skin appears normal.

Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor.

LENUS (Irish Health Repository)

Tamagno, Gianluca

2013-10-01

According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Hee; Lee, Chang Ki [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Oral Cancer Research Institute, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Hwang, Young Sun [Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Park, Kwang-Kyun [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Chung, Won-Yoon [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of)], E-mail: wychung@yuhs.ac

2008-07-03

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H{sub 2}O{sub 2} formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-{kappa}B) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-{kappa}B activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-{kappa}B signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent.

Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

International Nuclear Information System (INIS)

Park, Jae Hee; Lee, Chang Ki; Hwang, Young Sun; Park, Kwang-Kyun; Chung, Won-Yoon

2008-01-01

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H 2 O 2 formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-κB activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-κB signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent

Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores

Science.gov (United States)

Miller, Jessica P.; Habimana-Griffin, LeMoyne; Edwards, Tracy S.; Achilefu, Samuel

2017-06-01

Similarity of skin cancer with many benign skin pathologies requires reliable methods to detect and differentiate the different types of these lesions. Previous studies have explored the use of disparate optical techniques to identify and estimate the invasive nature of melanoma and basal cell carcinoma with varying outcomes. Here, we used a concerted approach that provides complementary information for rapid screening and characterization of tumors, focusing on squamous cell carcinoma (SCC) of the skin. Assessment of in vivo autofluorescence lifetime (FLT) imaging of endogenous fluorophores that are excitable at longer wavelengths (480 nm) than conventional NADH and FAD revealed a decrease in the short FLT component for SCC compared to normal skin, with mean values of 0.57±0.026 ns and 0.61±0.021 ns, respectively (p=0.004). Subsequent systemic administration of a near-infrared fluorescent molecular probe in SCC bearing mice, followed by the implementation of image processing methods on data acquired from two-dimensional and three-dimensional fluorescence molecular imaging, allowed us to estimate the tumor volume and depth, as well as quantify the fluorescent probe in the tumor. The result suggests the involvement of lipofuscin-like lipopigments and riboflavin in SCC metabolism and serves as a model for staging SCC.

Mechanism for initiation of food allergy: Dependence on skin barrier mutations and environmental allergen costimulation.

Science.gov (United States)

Walker, Matthew T; Green, Jeremy E; Ferrie, Ryan P; Queener, Ashley M; Kaplan, Mark H; Cook-Mills, Joan M

2018-02-15

Mechanisms for the development of food allergy in neonates are unknown but clearly linked in patient populations to a genetic predisposition to skin barrier defects. Whether skin barrier defects contribute functionally to development of food allergy is unknown. The purpose of the study was to determine whether skin barrier mutations, which are primarily heterozygous in patient populations, contribute to the development of food allergy. Mice heterozygous for the filaggrin (Flg) ft and Tmem79 ma mutations were skin sensitized with environmental and food allergens. After sensitization, mice received oral challenge with food allergen, and then inflammation, inflammatory mediators, and anaphylaxis were measured. We define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations after brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have increased responses to suboptimal sensitization with food allergens. Importantly, responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. ST2 blockade during skin sensitization inhibited the development of anaphylaxis, antigen-specific IgE, and inflammatory mediators. Neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen, but interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early-life exposures and genetics in patients with clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Tumor Localization Using Cone-Beam CT Reduces Setup Margins in Conventionally Fractionated Radiotherapy for Lung Tumors

International Nuclear Information System (INIS)

Yeung, Anamaria R.; Li, Jonathan G.; Shi Wenyin; Newlin, Heather E.; Chvetsov, Alexei; Liu, Chihray; Palta, Jatinder R.; Olivier, Kenneth

2009-01-01

Purpose: To determine whether setup margins can be reduced using cone-beam computed tomography (CBCT) to localize tumor in conventionally fractionated radiotherapy for lung tumors. Methods and Materials: A total of 22 lung cancer patients were treated with curative intent with conventionally fractionated radiotherapy using daily image guidance with CBCT. Of these, 13 lung cancer patients had sufficient CBCT scans for analysis (389 CBCT scans). The patients underwent treatment simulation in the BodyFix immobilization system using four-dimensional CT to account for respiratory motion. Daily alignment was first done according to skin tattoos, followed by CBCT. All 389 CBCT scans were retrospectively registered to the planning CT scans using automated soft-tissue and bony registration; the resulting couch shifts in three dimensions were recorded. Results: The daily alignment to skin tattoos with no image guidance resulted in systematic (Σ) and random (σ) errors of 3.2-5.6 mm and 2.0-3.5 mm, respectively. The margin required to account for the setup error introduced by aligning to skin tattoos with no image guidance was approximately 1-1.6 cm. The difference in the couch shifts obtained from the bone and soft-tissue registration resulted in systematic (Σ) and random (σ) errors of 1.5-4.1 mm and 1.8-5.3 mm, respectively. The margin required to account for the setup error introduced using bony anatomy as a surrogate for the target, instead of localizing the target itself, was 0.5-1.4 cm. Conclusion: Using daily CBCT soft-tissue registration to localize the tumor in conventionally fractionated radiotherapy reduced the required setup margin by up to approximately 1.5 cm compared with both no image guidance and image guidance using bony anatomy as a surrogate for the target.

Skin acceptability of a cosmetic moisturizer formulation in female subjects with sensitive skin

Directory of Open Access Journals (Sweden)

Nisbet SJ

2018-04-01

Full Text Available Stephanie J Nisbet Skin Health Medical Affairs, GSK Consumer Healthcare, Weybridge, Surrey, UK Purpose: This 3-week, open-label, noncomparative clinical study evaluated the skin acceptability of a cosmetic moisturizer in subjects with sensitive skin, by monitoring adverse events (AEs and cutaneous discomfort related to normal usage.Materials and methods: Female subjects aged between 18–60 years, with Fitzpatrick phototype classification I–IV and sensitive skin, verified by a positive reaction on the stinging test at screening, were included. Subjects applied the moisturizer to their face and body twice daily for 21±2 days at home and recorded study product usage and feelings of cutaneous discomfort (eg, dryness, prickling, stinging, and itching in a diary; any AEs were reported to the clinic. At study end, skin acceptability of the moisturizer was investigator-assessed based on the nature of AEs and subjects’ self-reported feelings of discomfort, and by clinical evaluation of skin reactions in the area of moisturizer application (appearance of erythema, formation of edema, and skin desquamation; scored according to an adapted Draize and Kligman scale. Only subjects with a treatment compliance of ≥80% were included in the final analysis.Results: In total, 35 subjects initiated and completed the study; all were compliant to the minimum study product usage. Per investigator clinical dermatological assessment at study end, none of the 35 subjects had skin reactions in the area of moisturizer application and there were no reported AEs. One subject reported sensations of mild prickling and itching immediately after applying the moisturizer (not classified as AEs, which spontaneously remitted after complete absorption of the product and were noted only in exposed areas. These events were considered by the investigator as being possibly/probably related to the use of study product; however, no clinical signs of skin reaction were observed in

Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor initiation.

Science.gov (United States)

Zhao, Yuewei; Xia, Qingsu; Gamboa da Costa, Gonçalo; Yu, Hongtao; Cai, Lining; Fu, Peter P

2012-09-17

Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids are among the first chemical carcinogens identified in plants. Previously, we determined that metabolism of pyrrolizidine alkaloids in vivo and in vitro generated a common set of DNA adducts that are responsible for tumor induction. Using LC-ESI/MS/MS analysis, we previously determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4) were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid. Because of the lack of an adequate amount of authentic standards, the structures of DHP-dA-3 and DHP-dA-4 were not elucidated, and the structural assignment for DHP-dG-4 warranted further validation. In this study, we developed an improved synthetic methodology for these DNA adducts, enabling their full structural elucidation by mass spectrometry and NMR spectroscopy. We determined that DHP-dA-3 and DHP-dA-4 are a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl) dehydrosupinidine, while DHP-dG-4 is 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine, an epimer of DHP-dG-3. With the structures of these DNA adducts unequivocally elucidated, we conclude that cellular DNA preferentially binds dehydropyrrolizidine alkaloid, for example, dehydroriddelliine, at the C9 position of the necine base, rather than at the C7 position. We also determined that DHP-dA-3 and DHP-dA-4, as well as DHP-dG-3 and DHP-dG-4, are interconvertible. This study represents the first report with detailed structural assignments of the DNA adducts that are responsible for pyrrolizidine alkaloid tumor induction on the molecular level. A mechanism of tumor initiation by pyrrolizidine alkaloids is consequently fully determined.

The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing.

Science.gov (United States)

Belvedere, Raffaella; Bizzarro, Valentina; Parente, Luca; Petrella, Francesco; Petrella, Antonello

2017-07-25

Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma ® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan and Prisma ® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that mesoglycan and Prisma ® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma ® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses.

The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing

Directory of Open Access Journals (Sweden)

Raffaella Belvedere

2017-07-01

Full Text Available Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan and Prisma® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that mesoglycan and Prisma® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses.

Photodynamic therapy using a novel irradiation source, LED lamp, is similarly effective to photodynamic therapy using diode laser or metal-halide lamp on DMBA- and TPA-induced mouse skin papillomas.

Science.gov (United States)

Takahashi, Hidetoshi; Nakajima, Susumu; Ogasawara, Koji; Asano, Ryuji; Nakae, Yoshinori; Sakata, Isao; Iizuka, Hajime

2014-08-01

Photodynamic therapy (PDT) is useful for superficial skin tumors such as actinic keratosis and Bowen disease. Although PDT is non-surgical and easily-performed treatment modality, irradiation apparatus is large and expensive. Using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-ο-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin papilloma model, we compared the efficacy of TONS501- and ALA-PDT with a LED lamp, a diode laser lamp or a metal-halide lamp on the skin tumor regression. TONS501-PDT using 660 nm LED lamp showed anti-tumor effect at 1 day following the irradiation and the maximal anti-tumor effect was observed at 3 days following the irradiation. There was no significant difference in the anti-tumor effects among TONS501-PDT using LED, TONS501-PDT using diode laser, and 5-aminolevulinic acid hydrochloride (ALA)-PDT using metal-halide lamp. Potent anti-tumor effect on DMBA- and TPA-induced mouse skin papilloma was observed by TONS501-PDT using 660 nm LED, which might be more useful for clinical applications. © 2014 Japanese Dermatological Association.

Use dibunol therapy for radiation injuries of the skin and mucous membranes

Energy Technology Data Exchange (ETDEWEB)

Agafonova, G.B.; Barsel' , V.A.; Sarkisyan, Yu.Kh.; Terekhova, G.S.; Podlyashchuk, E.L.; Ustinova, V.F. (Nauchno-Issledovatel' skij Inst. Rentgenologii i Radiologii, Moscow (USSR); AN SSSR, Moscow. Inst. Khimicheskoj Fiziki)

1983-04-01

There are presented the results of the use of dibunol in the form of liniment (1-10%) for the treatment of radiation cystitis and rectitis resulting from radiation therapy of small pelvic tumors, epidermitis and epithelitis that develop in the course of treatment of skin and lower lip tumors. A high efficacy of the drug in the therapy of radiation injury has been shown in 212 patients.

Adnexal Tumors of Skin: An Experience at a Tertiary Care Center at ...

African Journals Online (AJOL)

The concordance of clinical and histopathological diagnosis was also assessed. Results: Most of the ATs were benign (24/25) with head and neck being the most common location (72%). Nearly 56% of the tumors exhibited sweat gland differentiation, 28% hair follicle differentiation, and sebaceous gland tumors accounted ...

Left Transperitoneal Adrenalectomy with a Laparoendoscopic Single-Site Surgery Combined Technique: Initial Case Reports

Directory of Open Access Journals (Sweden)

Yasuhiro Sumino

2011-01-01

Full Text Available Laparoendoscopic single-site surgery (LESS is a step toward the development of minimally invasive surgery. It is initially difficult for surgeons with limited experience to perform the surgery. We describe two cases of left adrenalectomy with a LESS combined with the addition of an accessory port. After a 2.5-cm skin incision was made at the level of the paraumbilicus to insert the primary 12-mm trocar for the laparoscope, a 5-mm nonbladed trocar was placed through the skin incision side-by-side with the primary trocar. A second 3-mm nonbladed trocar was then placed along the anterior axillary line; a multichannel trocar was not used as a single port. Both adrenalectomies were completed successfully. In patients with a minor adrenal tumor, a combined technique using LESS and an additional port is easier than LESS alone and may, therefore, be a bridge between the conventional laparoscopic approach and LESS.

High frequency ultrasonography of the skin and its role as an auxillary tool in diagnosis of benign and malignant cutaneous tumors--a comparison of two clinical cases.

Science.gov (United States)

Dybiec, Ewa; Pietrzak, Aldona; Adamczyk, Michal; Michalska-Jakubus, Malgorzata; Wawrzycki, Bartlomiej; Lotti, Torello; Rutkowski, Piotr; Krasowska, Dorota

2015-01-01

The number of dermatologic entities that can be studied by ultrasound examination (US) of the skin is increasing. Conventional US and high frequency US (HFUS) are considered useful additional tools in improving the diagnosis and management of common benign and malignant skin tumors. US may help in positive and differential diagnosis of primary melanocytic neoplasms and of locoregional spread in melanoma patients. US preoperative evaluation of primary melanoma thickness correlates with histologically estimated melanoma thickness, and can help determine surgical margins and indications for sentinel lymph node biopsy. It is also useful during follow-up after surgical treatment for early detection of recurrence or metastases. In this case report, we present two cases of skin lesions clinically suspicious for malignancy. The first lesion was a round nodule 3 mm in diameter, resembling a blue nevus. In HFUS it was well delimited, hypoechoic, and well vascularized. The second lesion presented as an elevated, well-circumscribed nodule, 5-6 mm in diameter, inhomogeneous in color. HFUS depicted a poorly delimited, irregular, hypoechoic lesion crossing the dermoepidermal junction. At the first exam it was not vascularized, but 6 months later a number of vascular flow signals within the lesion were found. In histopathological examination the lesions were finally diagnosed as, respectively: benign cavernous hemangioma and melanoma. In both presented cases HFUS proved to be useful in a differential diagnosis of suspicious skin lesions. Noninvasive and easy to perform, HFUS is a valuable diagnostic method in dermatology.

Effect of Fe3O4 Nanoparticles on Skin Tumor Cells and Dermal Fibroblasts

Directory of Open Access Journals (Sweden)

Lirija Alili

2015-01-01

Full Text Available Iron oxide (Fe3O4 nanoparticles have been used in many biomedical approaches. The toxicity of Fe3O4 nanoparticles on mammalian cells was published recently. Though, little is known about the viability of human cells after treatment with Fe3O4 nanoparticles. Herein, we examined the toxicity, production of reactive oxygen species, and invasive capacity after treatment of human dermal fibroblasts (HDF and cells of the squamous tumor cell line (SCL-1 with Fe3O4 nanoparticles. These nanoparticles had an average size of 65 nm. Fe3O4 nanoparticles induced oxidative stress via generation of reactive oxygen species (ROS and subsequent initiation of lipid peroxidation. Furthermore, the question was addressed of whether Fe3O4 nanoparticles affect myofibroblast formation, known to be involved in tumor invasion. Herein, Fe3O4 nanoparticles prevent the expression alpha-smooth muscle actin and therefore decrease the number of myofibroblastic cells. Moreover, our data show in vitro that concentrations of Fe3O4 nanoparticles, which are nontoxic for normal cells, partially reveal a ROS-triggered cytotoxic but also a pro-invasive effect on the fraction of squamous cancer cells surviving the treatment with Fe3O4 nanoparticles. The data herein show that the Fe3O4 nanoparticles appear not to be adequate for use in therapeutic approaches against cancer cells, in contrast to recently published data with cerium oxide nanoparticles.

Skin cancer of Nagasaki atomic bomb survivors, 4

International Nuclear Information System (INIS)

Sadamori, Naoki; Mine, Mariko; Hori, Makoto; Noda, Yoshinori; Fujiwara, Naoko; Takahara, Osamu; Sadamori, Michiko; Nishimoto, Katsutaro; Ota, Hisahiro.

1990-01-01

We previously reported that there was a high correlation between the exposure dose and the incidence of skin cancer in A-bomb survivors using the data of the Nagasaki Life Span Study of Radiation Effects Research Foundation and Nagasaki Tumor Registry. In Report 3 of this series, we clarified that the correlation between the exposure distance and the incidence of skin cancer was statistically significant in 140 cases of skin cancer collected from 31 hospitals in Nagasaki City and adjacent districts on the basis of the data of the total 66,276 A-bomb survivors recorded in the Scientific Data Center of Atomic Bomb Disaster, Nagasaki University School of Medicine, and that the correlation was the same even when the cases were divided by sex. In this report, we examined the chronological change of the incidence of skin cancer in Nagasaki A-bomb survivors, using the data of the Scientific Data Center of Atomic Bomb Disaster. It is likely that the incidence of skin cancer in Nagasaki A-bomb survivors has increased after 1962, especially after 1975 in those exposed within 2.5km from the hypocenter compared to those exposed at 3.0km or more. (author)

Initial treatment results using cyberknife for head and neck tumor

International Nuclear Information System (INIS)

Himei, Kengo; Katsui, Kuniaki; Yoshida, Atsushi; Takemoto, Mitsuhiro; Kobayashi, Mitsuru; Kuroda, Masahiro; Hiraki, Yoshio

2002-01-01

The CyberKnife, a medical device for stereotactic radiotherapy, is composed of a combination of a robot manipulator and LINAC. For the treatment of head and neck tumors, this system has been applied. Between June 2000 and January 2001, 18 patients with head and neck tumor were treated with this system because of tumor recurrence, difficulty in surgery or additional increase after external radiotherapy. The median age was 64 years. Primary lesions were skull base (4), nasopharynx (3), paranasal sinus (3), nasal cavity (2), lacrimal gland (1), oropharynx (1), oral floor (1), and buccul mucosa (1), metastatic lymph nodes were found in three. The prescribed dose was 12-38 Gy as for marginal dose. The response rate (CR+PR) was 44.4% and local control rate (CR+PR+NC) was 77.8%. The adverse effects were assessed by the NCI-CTC Version 2.0 and observed grade 3 in two cases. Our early experience indicates that this system could to be feasible for the treatment of locally advanced or recurrent head and neck tumor, and for the reduction of adverse effect and maintenance of useful QOL of patients. (author)

Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

Energy Technology Data Exchange (ETDEWEB)

Siddens, Lisbeth K.; Larkin, Andrew [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Krueger, Sharon K. [Superfund Research Center, Oregon State University (United States); The Linus Pauling Institute, Oregon State University (United States); Bradfield, Christopher A. [McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706 (United States); Waters, Katrina M.; Tilton, Susan C. [Superfund Research Center, Oregon State University (United States); Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Pereira, Cliff B. [Superfund Research Center, Oregon State University (United States); Deptartment of Statistics, Oregon State University, Corvallis, OR 97331 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Löhr, Christiane V. [Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Arlt, Volker M.; Phillips, David H. [Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King' s College London, London SE1 9NH (United Kingdom); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); The Linus Pauling Institute, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); and others

2012-11-01

The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by {sup 32}P post‐labeling, did not correlate with tumor incidence. PAH‐dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p < 0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique

Behavior and biological action of 239Pu while getting into skin abrasions

International Nuclear Information System (INIS)

Bazhin, A.G.; Lyubchanskij, Eh.R.; Nifatov, A.N.; Sinyakov, E.G.

1983-01-01

The levels of the radionuclide resorption are given through abrasions in applying 224-906 kBk of 239 Pu on them (0.6=1.5 % for 600 days), the nature of distribution and parameters of its exchange in the test skin area, skeleton and liver. Data of morphological studies are presented. The influence of prolonged complexon therapy on 239 Pu content in organs and tissues, mean life span, the frequency of appearance of morphological changes in test skin areas with the contamination density of 40; 184 and 722 kBk of 239 Pu/cm 2 and the frequency of tumor development including malignancy in case of applying 224 and 906 kBk of 239 Pu to abrasions is evaluated. It has been established that as a result of complexon therapy dosage exposure of the skeleton lessened by 4-5 times, the mean life span of rats with tumors increased, the development of osteosarcomas caused by Pu reduced from 23.6-36.2 to 4.4-6.2 % but the therapy did not influence the frequency of pathological changes in the test skin area

Ability of m-chloroperoxybenzoic acid to induce the ornithine decarboxylase marker of skin tumor promotion and inhibition of this response by gallotannins, oligomeric proanthocyanidins, and their monomeric units in mouse epidermis in Vivo

Science.gov (United States)

Guilan Chen; Elisabeth M. Perchellet; Xiao Mei Gao; Steven W. Newell; richard W. Hemingway; Vittorio Bottari; Jean-Pierre Perchellet

1995-01-01

m-Chloroperoxybenzoic acid (CPBA) was tested for its ability to induce the ornithine decarboxylase (ODC) marker of skin tumor promotion. In contrast to benzoyl peroxide, dicumyl peroxide, and 2-butanol peroxide, 5 mg of CPBA applied twice at a 72-h interval induce ODC activity at least as much as 3 ug of 12-O-tetradecanoylphorbol-13-acetate (TPA). ODC induction peaks...

Chimeric Monoclonal Antibody Cetuximab Targeting Epidermal Growth Factor-Receptor in Advanced Non-Melanoma Skin Cancer.

Science.gov (United States)

Wollina, Uwe; Tchernev, Georgi; Lotti, Torello

2018-01-25

Non-melanoma skin cancer (NMSC) is the most common malignancy in humans. Targeted therapy with monoclonal antibody cetuximab is an option in case of advanced tumor or metastasis. We present and update of the use of cetuximab in NMSC searching PUBMED 2011-2017. The monoclonal antibody cetuximab against epidermal growth factor receptor (EGFR) has been investigated for its use in NMSC during the years 2011 to 2017 by a PUBMED research using the following items: "Non-melanoma skin cancer AND cetuximab," "cutaneous squamous cell carcinoma AND cetuximab," and "basal cell carcinoma AND cetuximab", and "cetuximab AND skin toxicity". Available data were analyzed including case reports. Current evidence of cetuximab efficacy in NMSC was mainly obtained in cutaneous SCC and to a lesser extend in BCC. Response rates vary for neoadjuvant, adjuvant, mono- and combined therapy with cetuximab. Management of cutaneous toxicities is necessary. Guidelines are available. Cetuximab is an option for recurrent or advanced NMSC of the skin. It seems to be justified particularly in very high-risk tumors. There is a need for phase III trials.

Biological stoichiometry in tumor micro-environments.

Directory of Open Access Journals (Sweden)

Irina Kareva

Full Text Available Tumors can be viewed as evolving ecological systems, in which heterogeneous populations of cancer cells compete with each other and somatic cells for space and nutrients within the ecosystem of the human body. According to the growth rate hypothesis (GRH, increased phosphorus availability in an ecosystem, such as the tumor micro-environment, may promote selection within the tumor for a more proliferative and thus potentially more malignant phenotype. The applicability of the GRH to tumor growth is evaluated using a mathematical model, which suggests that limiting phosphorus availability might promote intercellular competition within a tumor, and thereby delay disease progression. It is also shown that a tumor can respond differently to changes in its micro-environment depending on the initial distribution of clones within the tumor, regardless of its initial size. This suggests that composition of the tumor as a whole needs to be evaluated in order to maximize the efficacy of therapy.

Tumorigenic action of beta, proton, alpha, and electron radiation on the rat skin. Progress report, August 1, 1974--July 31, 1975

International Nuclear Information System (INIS)

Albert, R.E.; Burns, F.J.

1975-01-01

The carcinogenic effects of ionizing radiation (α, β, electron, and protons) on rat skin were studied in an attempt to learn more about radiation carcinogenesis, especially how various parameters of the irradiation, such as dose distribution within the tissue and dose rate, affect the yield of tumors. It was found that when the dose was localized to a small region of skin, the tumor yield was reduced and the magnitude of the reduction indicated that the region of reduced response might extend about 150 μ into the irradiated zone. The proliferative state of the hair follicles at the time of irradiation had relatively little effect on tumor induction although old animals were less susceptible than young or newborn animals. The penetration requirement of at least 0.3 mm for producing tumors suggests that the hair follicle germ cells could be the oncogenic targets. Comprehensive experiments to measure the rate of recovery for tumor induction in split-dose exposure protocols indicated a recovery halftime of about 4 hrs for electrons and significant recovery for protons, which was used in a model to predict how recovery should affect the tumor response at low dose rates. Combinations of ionizing radiation and ultraviolet light were applied to rat skin to determine whether they are additive for producing tumors. (U.S.)

Effects of experimental radiotherapy and hyperthermia on tumors and normal tissues in small animals

International Nuclear Information System (INIS)

Wondergem, J.

1985-01-01

Experiments on responses of tumors, implanted subcutaneously in the leg, to irradiation alone or combined with heat are reported. The influence of factors modifying the fraction of hypoxic cells (e.g. anesthesia of the animal and tumor volume) is also discussed. The radiosensitivity of developing lung tumors was examined for spontaneous as well as for artificial lung metastases. Both experimental tumor models were compared with regard to their value in experimental radiotherapy. Data obtained on the response of artificial metastases and lung tissue to combined treatment with irradiation and several drugs are presented. Data on damage of the mouse foot, as a result of heat and/or irradiation treatments are presented. In particular the influence of thermotolerance on thermal enhancement of the radiation induced skin reaction was studied. Tolerance of the skin of previously irradiated mice to retreatment with irradiation, to hyperthermia alone and combined with X-rays was assessed. (Auth.)

The organisation and role of the Euro skin bank

International Nuclear Information System (INIS)

Van Baare, J.

1999-01-01

In the treatment of burns, either superficial or deep, partial or full thickness, where sufficient autograft is lacking, wound covering by fresh or stored allogencic human skin is currently preferred over the use of (bio-) synthetic dressings by most physicians involved in burn care. Several methods to preserve, store and provide sufficient quantities of allograft (homo- or xeno-) at any given time have been developed over the last decades and have been extensively documented. Skin banks differ in their mode of operation (local, regional, national and international) and the techniques applied for preservation and storage of human skin. The Dutch National Skin Bank was established in 1976 as a subsidiary to the Dutch Bums Foundation with no other goal than providing human allograft skin for the treatment of bum victims to the Red Cross Hospital Bum Unit and later to other Dutch bum centres and general hospitals. The initial preservation technique the skin bank used was cryopreservation. In 1984 there was an important change in the preservation technique. Based on literature high concentrations of glycerol were introduced to preserve human skin for long-term storage. Meanwhile, a gradual increase in the yearly number of skin donors from 1984 onwards was observed, and by 1989 regular requests from bum centres in other countries for glycerol preserved donor skin were received. In 1992 the skin bank changed their name into Euro Skin Bank to express their international collaboration. The Euro Skin Bank operates on a non-profit basis and was until recently dependent on financial support of the Dutch Bums Foundation. Due to the large amount of requests for donor skin, the Euro Skin Bank started to set up satellite skin banks in various European countries. With this initiative it was not only possible to help the specific countries to supply their own bum centres with allograft skin, but also an amount of skin was send back to the Euro Skin Bank in order to distribute the

Systematic skin cancer screening in Northern Germany.

Science.gov (United States)

Breitbart, Eckhard W; Waldmann, Annika; Nolte, Sandra; Capellaro, Marcus; Greinert, Ruediger; Volkmer, Beate; Katalinic, Alexander

2012-02-01

The incidence of skin cancer is increasing worldwide. For decades, opportunistic melanoma screening has been carried out to respond to this burden. However, despite potential positive effects such as reduced morbidity and mortality, there is still a lack of evidence for feasibility and effectiveness of organized skin cancer screening. The main aim of the project was to evaluate the feasibility of systematic skin cancer screening. In 2003, the Association of Dermatological Prevention was contracted to implement the population-based SCREEN project (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) in the German state of Schleswig-Holstein. A two-step program addressing malignant melanoma and nonmelanocytic skin cancer was implemented. Citizens (aged ≥ 20 years) with statutory health insurance were eligible for a standardized whole-body examination during the 12-month study period. Cancer registry and mortality data were used to assess first effects. Of 1.88 million eligible citizens, 360,288 participated in SCREEN. The overall population-based participation rate was 19%. A total of 3103 malignant skin tumors were found. On the population level, invasive melanoma incidence increased by 34% during SCREEN. Five years after SCREEN a substantial decrease in melanoma mortality was seen (men: observed 0.79/100,000 and expected 2.00/100,000; women: observed 0.66/100,000 and expected 1.30/100,000). Because of political reasons (resistance as well as lack of support from major German health care stakeholders), it was not possible to conduct a randomized controlled trial. The project showed that large-scale systematic skin cancer screening is feasible and has the potential to reduce skin cancer burden, including mortality. Based on the results of SCREEN, a national statutory skin cancer early detection program was implemented in Germany in 2008. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All

Epidemiology of skin cancer.

Science.gov (United States)

Leiter, Ulrike; Eigentler, Thomas; Garbe, Claus

2014-01-01

Melanoma and nonmelanoma skin cancer (NMSC) are now the most common types of cancer in white populations. Both tumor entities show an increasing incidence rate worldwide but a stable or decreasing mortality rate. NMSC is the most common cancer in white-skinned individuals with a worldwide increasing incidence. NMSC is an increasing problem for health care services worldwide which causes significant morbidity. The rising incidence rates of NMSC are probably caused by a combination of increased exposure to ultraviolet (UV) or sun light, increased outdoor activities, changes in clothing style, increased longevity, ozone depletion, genetics and in some cases, immune suppression. An intensive UV exposure in childhood and adolescence was causative for the development of basal cell carcinoma (BCC) whereas for the etiology of SCC a chronic UV exposure in the earlier decades was accused. Cutaneous melanoma is the most rapidly increasing cancer in white populations, in the last 3 decades incidence rates have risen up to 5-fold. In 2008 melanoma was on place 5 in women and on place 8 in men of the most common solid tumor entities in Germany. The frequency of its occurrence is closely associated with the constitutive color of the skin, and the geographical zone. Changes in outdoor activities and exposure to sunlight during the past 50 years are an important factor for the increasing incidence of melanoma. Mortality rates of melanoma show a stabilization in the USA, Australia and also in European countries. In contrast to SCC, melanoma risk seems to be associated with an intermittent exposure to sunlight. Prevention campaigns aim on reducing incidence and achieving earlier diagnosis, which resulted in an ongoing trend toward thin melanoma since the last two decades. However, the impact of primary prevention measures on incidence rates of melanoma is unlikely to be seen in the near future, rather increasing incidence rates to 40-50/100,000 inhabitants/year should be expected in

Targeted Therapy in Nonmelanoma Skin Cancers

International Nuclear Information System (INIS)

Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio

2011-01-01

Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC

Targeted Therapy in Nonmelanoma Skin Cancers

Directory of Open Access Journals (Sweden)

Giulia Spallone

2011-05-01

Full Text Available Nonmelanoma skin cancer (NMSC is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC, representing around 75% of NMSC and Squamous Cell Carcinomas (SCC. The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

Acral peeling skin syndrome: report of two cases.

Science.gov (United States)

García, Elena García; Carreño, Rosario Granados; Martínez González, Miguel A; Reyes, José Jiménez

2005-01-01

Peeling skin syndrome is a rare dermatosis characterized by spontaneous and painless peeling of the skin. The authors report two patients with history of spontaneous, asymptomatic, and noninflammatory peeling skin of the acral surfaces after soaking in water. On light microscopy, blisters were located in the mid layers of the stratum corneum, above the granular layer. Ultrastructural examination revealed increased intercellular lipids and abnormal, "moth-eaten," keratohyalin granules, but the authors were unable to determine whether the separation initiated within the horny cells or between adjacent cells. These patients represented a localized variant of peeling skin syndrome.

Rare cancers in children - The EXPeRT Initiative: a report from the European Cooperative Study Group on Pediatric Rare Tumors.

Science.gov (United States)

Bisogno, G; Ferrari, A; Bien, E; Brecht, I B; Brennan, B; Cecchetto, G; Godzinski, J; Orbach, D; Reguerre, Y; Stachowicz-Stencel, T; Schneider, D T

2012-10-01

The low incidence and the heterogeneity of very rare tumors (VRTs) demand for international cooperation. In 2008, EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) was founded by national groups from Italy, France, United Kingdom, Poland and Germany. The first aims of EXPeRT were to agree on a uniform definition of VRTs and to develop the currently most relevant scientific questions. Current initiatives include international data exchange, retrospective and prospective studies of specific entities, and the development of harmonized and internationally recognized guidelines. Moreover, EXPeRT established a network for expert consultation to assist in clinical decision in VRTs. © Georg Thieme Verlag KG Stuttgart · New York.

Tumor-associated proteins in rat submandibular gland induced by DMBA and irradiation

International Nuclear Information System (INIS)

Oh, Sung Ook; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

1997-01-01

This study was performed in order to identify changes of the plasma membrane proteins in rat submandibular gland tumors induced by 7,12-dimethylbenz[a]anthracene [DMBA] and X-irradiation. Two kinds of tumor associated membrane proteins (protein A and B) were isolated with 3 M KCl extraction from rat submandibular gland tumors induced by DMBA and X-irradiation. To identify their antigenicities, immunoelectrophoresis and double immunodiffusion was carried out with various proteins extracted from liver, heart, skin and pancreas of adult rats and from embryonic liver, heart and skin. The rabbit antisera against the protein A did not cross-react with any of the proteins extracted from the above mentioned tissues, suggesting that protein A might be tumor specific antigen. However, the rabbit antisera against protein B was precipitated with proteins extracted from the liver of adult and embryonic rats. Polyacrylamide gel electrophoresis of these two proteins (A and B) showed that protein A was a dimer with molecular weights of 69,000 and 35,000 dalton, whereas protein B was a monomer with molecular weight of 50,000 dalton.

Ultraviolet light exposure and skin cancer in the city of Arica, Chile.

Science.gov (United States)

Rivas, Miguel; Araya, María C; Durán, Viviava; Rojas, Elisa; Cortes, Juan; Calaf, Gloria M

2009-01-01

An increase in the amount of solar ultraviolet light that reaches the Earth is considered to be responsible for the worldwide increase in skin cancer. Solar ultraviolet B (UVB) light (290-320 nm) has multiple effects that can be harmful to human beings. The city of Arica in Chile receives high UV levels. This can explain the high prevalence of skin cancer in the Arica population. In the present study, pathological reports of skin cancer were collected from an Arica hospital and retrospectively examined to investigate the possible effects of UV radiation. Among the malignant skin tumor types, basocellular and spinocellular carcinomas were more common in men (44.4 and 16.6%, respectively) than in women (24.9 and 10.7%, respectively). Basocellular carcinoma was observed in individuals 40-79 years of age. The incidence of skin cancer significantly increased (Plight to which individuals are exposed throughout the year, and the cumulative effect of this type of radiation on the skin.

Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors

Science.gov (United States)

Beckhove, Philipp; Feuerer, Markus; Dolenc, Mathias; Schuetz, Florian; Choi, Carmen; Sommerfeldt, Nora; Schwendemann, Jochen; Ehlert, Katrin; Altevogt, Peter; Bastert, Gunther; Schirrmacher, Volker; Umansky, Viktor

2004-01-01

Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA–CD62L+ or CD45RA–CD62L–, respectively). To test their in vivo function, we separated bone marrow–derived CD45RA+ naive or CD45RA–CD45RO+ memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA– memory but not CD45RA+ naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin+ tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells. PMID:15232613

The use dibunol therapy for radiation injuries of the skin and mucous membranes

International Nuclear Information System (INIS)

Agafonova, G.B.; Barsel', V.A.; Sarkisyan, Yu.Kh.; Terekhova, G.S.; Podlyashchuk, E.L.; Ustinova, V.F.; AN SSSR, Moscow. Inst. Khimicheskoj Fiziki)

1983-01-01

There are presented the results of the use of dibunol in the form of liniment (1-10%) for the treatment of radiation cystitis and rectitis resulting from radiation therapy of small pelvic tumors, epidermitis and epithelitis that develop in the course of treatment of skin and lower lip tumors. A high efficacy of the drug in the therapy of radiation injury has been shown in 212 patients

Superficial skin ulcers

International Nuclear Information System (INIS)

Samaila, Modupeola O.; Rafindadi, Abdulmumini H.; Oluwole, Olabode P.; Adewuyi, Sunday A.

2007-01-01

Objective was to determine the underlying cause of superficial skin ulcers over a 15-year period. A retrospective histopathological analysis of 670 cases of superficial skin ulcers diagnosed in the Dept. of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria from January 1991 to December 2005. A total of 670 superficial skin ulcers were analyzed. The mail to female gender ratio was 409:261(1.5:1.0) and a peakage frequency of 44.3 %( 297) in the 5th and 6th decades. Spectrum of lesions encountered was categorized into inflammatory, infections, benign and malignant diseases. The malignant lesions were 309 (46.1%), non-specific inflammation 302 (45.1%), granulation tissue 25 (3.7%) and pseudoepitheliomatous hyperplasia 14 (2.1%). A total of 18(2.7%) specific infections were encountered, which included bacterial, fungal and viral infection. Benign lesions were 2(0.3%), comprising of neurofibroma and Bowen's disease. The most common malignant lesion was squamous cell carcinoma 203 (30.3%) with a male to female ratio of 128:75 (1.7:1.0). Of these 161 were well differentiated tumors. The lower limb was the prevalent site distribution of all the ulcers. Superficial ulcers may be harbinger of malignant diseases. Squamous cell carcinoma remains the most common malignant lesion arising from chronic superficial ulcers from our setting. Adequate tissue biopsy and early diagnosis may reduce the attendant morbidity of these ulcers. (author)

Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

International Nuclear Information System (INIS)

Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

1989-01-01

The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors

Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

Energy Technology Data Exchange (ETDEWEB)

Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

1989-05-01

The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors.

Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers | Office of Cancer Genomics

Science.gov (United States)

Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown. Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis.

Brown tumors of the anterior skull base as the initial manifestation of true normocalcemic primary hyperparathyroidism: report of three cases and review of the literature.

Science.gov (United States)

Khalatbari, Mahmoud Reza; Hamidi, Mehrdokht; Moharamzad, Yashar; Setayesh, Ali; Amirjamshidi, Abbas

2013-01-01

Brown tumor is a bone lesion secondary to hyperparathyroidism of various etiologies. Skeletal involvement in primary hyperparathyroidism secondary to parathyroid adenoma is very uncommon and brown tumor has become extremely a rare clinical entity. Hyperparathyroidism is usually associated with high levels of serum calcium. Brown tumor as the only and initial symptom of normocalcemic primary hyperparathyroidism is extremely rare. Moreover, involvement of the skull base and the orbit is exceedingly rare. The authors would report three cases of brown tumor of the anterior skull base that were associated with true normocalcemic primary hyperparathyroidism. Clinical manifestations, neuroimaging findings, pathological findings, diagnosis and treatment of the patients are discussed and the relevant literature is reviewed.

Thermal interaction of short-pulsed laser focused beams with skin tissues

International Nuclear Information System (INIS)

Jiao Jian; Guo Zhixiong

2009-01-01

Time-dependent thermal interaction is developed in a skin tissue cylinder subjected to the irradiation of a train of short laser pulses. The skin embedded with a small tumor is stratified as three layers: epidermis, dermis and subcutaneous fat with different optical, thermal and physiological properties. The laser beam is focused to the tumor site by an objective lens for thermal therapy. The ultrafast radiation heat transfer of the focused beam is simulated by the transient discrete ordinates method. The transient Pennes bio-heat equation is solved numerically by the finite volume method with alternating direction implicit scheme. Emphasis is placed on the characterization of the focused beam propagation and absorption and the temperature rise in the focal spot. The effects of the focal spot size and location, the laser power, and the bio-heat equation are investigated. Comparisons with collimated irradiation are conducted. The focused beam can penetrate a greater depth and produce higher temperature rise at the target area, and thus reduce the possibility of thermal damage to the surrounding healthy tissue. It is ideal for killing cancerous cells and small tumors.

Thermal interaction of short-pulsed laser focused beams with skin tissues

Energy Technology Data Exchange (ETDEWEB)

Jiao Jian; Guo Zhixiong [Department of Mechanical and Aerospace Engineering, Rutgers, State University of New Jersey, Piscataway, NJ 08854 (United States)], E-mail: guo@jove.rutgers.edu

2009-07-07

Time-dependent thermal interaction is developed in a skin tissue cylinder subjected to the irradiation of a train of short laser pulses. The skin embedded with a small tumor is stratified as three layers: epidermis, dermis and subcutaneous fat with different optical, thermal and physiological properties. The laser beam is focused to the tumor site by an objective lens for thermal therapy. The ultrafast radiation heat transfer of the focused beam is simulated by the transient discrete ordinates method. The transient Pennes bio-heat equation is solved numerically by the finite volume method with alternating direction implicit scheme. Emphasis is placed on the characterization of the focused beam propagation and absorption and the temperature rise in the focal spot. The effects of the focal spot size and location, the laser power, and the bio-heat equation are investigated. Comparisons with collimated irradiation are conducted. The focused beam can penetrate a greater depth and produce higher temperature rise at the target area, and thus reduce the possibility of thermal damage to the surrounding healthy tissue. It is ideal for killing cancerous cells and small tumors.

Incidence of and risk factors for skin cancer after heart transplant

NARCIS (Netherlands)

Brewer, Jerry D.; Colegio, Oscar R.; Phillips, P. Kim; Roenigk, Randall K.; Jacobs, M. Amanda; van de Beek, Diederik; Dierkhising, Ross A.; Kremers, Walter K.; McGregor, Christopher G. A.; Otley, Clark C.

2009-01-01

OBJECTIVE: To examine the incidence, tumor burden, and risk factors for nonmelanoma and other skin cancer types in this heart transplant cohort. DESIGN: Retrospective review of patient medical records. SETTING: Tertiary care center. Patients All heart transplant recipients at Mayo Clinic from 1988

Chemoprevention of skin cancer by the flavonoid fraction of Saraca asoka.

Science.gov (United States)

Cibin, T R; Devi, D Gayathri; Abraham, Annie

2010-05-01

Saraca asoka (Family - Caesalpiniaceae) has been widely used in the Ayurvedic (traditional Indian) system of medicine especially due to its wound healing property. The present study investigated the chemopreventive property of flavonoids from the flowers of Saraca asoka on 7,12 dimethyl benz(a)anthracene (DMBA) induced skin cancer in mice models. A single topical application of DMBA (100 microg/50 microL of acetone) followed after 2 weeks by three times a week treatment with croton oil (1% in acetone), for 20 weeks resulted in tumor induction. The topical application of the flavonoid fraction of S. asoka (FF S. asoka), 30 min prior to the application of croton oil thrice weekly for 20 weeks, caused a significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also the latency period for the appearance of the first tumor was delayed by S. asoka pretreatment. In the flavonoid fraction (5 mg and 10 mg/kg body weight) treated animals, the levels of biochemical markers - rhodanese, myeloperoxidase, beta-D-glucuronidase, sialic acid, hexokinase and caspase 3 were significantly restored to near normal levels. These findings suggest the chemopreventive activity of flavonoids from S. asoka on two stage skin carcinogenesis. Histological data also support the chemopreventive potential of S. asoka. Copyright (c) 2009 John Wiley & Sons, Ltd.

Preliminary observations on differences in the Raman spectra of cancerous and noncancerous cells and connective tissue of human skin

Science.gov (United States)

Short, Michael A.; Lui, Harvey; McLean, David I.; Zeng, Haishan; Alajlan, Abdulmajeed; Chen, Michael X.

2005-04-01

A less invasive method of reliably detecting skin cancers is required. Raman spectroscopy is just one of several spectroscopic methods that look promising, but are not yet sufficiently reliable. More information is needed on how and why the Raman spectra of cancerous skin tissue is different from its normal counterpart. We have used confocal micro-Raman spectroscopy with a spatial resolution of about a micron to obtain spectra of unstained thin sections of human skin. We found that there were clear differences in the Raman spectra between cancerous and non-cancerous tissue both in cells and in the connective tissue. The DNA contribution to the spectra was generally stronger in malignant cells than normal ones. In regions of the dermis far away from the tumor one obtains the usual collagen spectra of normal skin, but adjacent to the tumor the spectra no longer appeared to be those of native collagen.

Skin-to-skin holding in the neonatal intensive care unit influences maternal milk volume.

Science.gov (United States)

Hurst, N M; Valentine, C J; Renfro, L; Burns, P; Ferlic, L

1997-01-01

To evaluate the effect of early initiation of skin-to-skin (STS) holding on lactation, we compared 24-hour milk volumes of mothers of ventilated low birth weight infants in an STS group to mothers in a non-STS control group. Mean 24-hour milk volumes at 2, 3, and 4 weeks after delivery of mothers participating in STS holding were compared with those of a retrospective control group from the 12-month period immediately preceding the introduction of STS holding in the neonatal intensive care unit. A repeated-measures analysis of variance adjusting for baseline volumes (1 week after delivery) was used to evaluate the difference in milk volumes between STS and control groups. Sixteen mothers initiated STS holding during the 2-month study period. Eight mothers met study criteria by initiating STS holding during the first 4 weeks after delivery. During a 2-week period the study group had a strong linear increase in milk volume in contrast to no indicative change of the control group's milk volume. STS holding of low birth weight infants initiated in the early intensive care phase can result in a significant increase in maternal milk volume, thereby overcoming the frequently seen insufficient lactation experienced by these mothers.

Disturbed skin barrier in children with chronic kidney disease.

Science.gov (United States)