Skin graft associated with platelet-rich plasma in correcting extensive injuries resulting from the resection of skin cancer chemically induced in rats

ABSTRACT Purpose: To evaluate whether using platelet-rich plasma (PRP) in the graft recipient bed after the resection of a neoplasia can influence its recurrence because this product stimulates angiogenesis, mitogenesis and chemotaxis. Methods: A study with 30 rats Wistar (Rattus norvegicus albinus), which were separated into group A (induction of carcinogenesis, PRP in the postoperative period) and group B (induction of carcinogenesis, absence of PRP in the postoperative period), with 15 animals in each. Carcinogenesis was induced on the skin of the animals' chest by the topical application of 0.5% dimethylbenzantracene (DMBA) diluted in acetone. After surgical resection of the induced neoplasia, PRP was used to stimulate angiogenesis before surgical wound synthesis. Data on the control and experimental groups and macroscopic and microscopic variables were evaluated using analysis of variance and the Tukey's test (5%). Results: It was possible to determine that the use of PRP is good in reconstructive surgeries, but it is contraindicated in patients during tumor resection, as it can cause changes in the surgical bed, in addition to stimulating recurrences and metastases. Conclusions: PRP may interact with tumour cells that were in the recipient site of the surgical wound during the resection of a neoplasia, and a local recurrence process can be triggered by applying this product.

Spitz nevus and infliximab: association or coincidence?

Abstract Biological therapies, including anti-TNF agents, are important in the treatment of various chronic inflammatory diseases, including psoriasis, rheumatoid arthritis or inflammatory bowel disease. The increased use of these drugs translates into an increasing awareness of its adverse effects, which include malignancy. In this paper, we describe the case of a 28-year-old woman who developed a spitzoid melanocytic tumor after starting infliximab therapy for ulcerative colitis. The evidence for causality between anti-TNF and melanocytic proliferations is still sparse; nonetheless, treatment-associated immunosuppression seems to play a key role in this phenomenon. Therefore, a regular follow-up with a rigorous skin examination is essential in these patients. Noninvasive techniques such as dermoscopy or reflectance confocal microscopy are particularly useful diagnostic tools in these circumstances.

Methotrexate and etanercept-induced primary cutaneous CD4 positive small/medium-sized pleomorphic T-cell lymphoma

Abstract: Immunosuppressive drugs and biological agents may represent a potential risk of lymphoma development in patients with rheumatoid arthritis. But most cases are diffuse, large B-cell lymphomas. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, a provisional entity in the 2005 WHO-EORTC classification of cutaneous lymphomas, is only described in a limited number of reports. To our knowledge, our case is a rare instance of primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, after associated treatment with methotrexate and etanercept, in a patient with moderate rheumatoid arthritis who had undergone an orchidectomy incorrectly.

Chemopreventive effect of Brazilian green propolis on experimental dermal carcinogenesis in murine model / Efecto quimiopreventivo del propóleos verde brasileño sobre la carcinogénesis cutánea en el modelo murino experimental

The aim of this study was to assess the effect of oral administration of Hydroalcoholic Extract of Green Propolis (HEGP) on dermal carcinogenesis in rodent model. For the biological assay, we used 36 mice, assigned into 6 groups (n=6): CTR (treated with 100 mg/kg HEGP and no tumor induction), TUM (treated with water and tumor induction), GP10 (treated with 10 mg/kg HEGP and tumor induction), GP50 (treated with 50 mg/kg HEGP and tumor induction) and GP100 (treated with 100 mg/kg HEGP and tumor induction). Cancer induction was performed in the back of the mice by topical application of DMBA. After 16 weeks, mice were euthanized and their backs were submitted to post-mortem histological analysis. The mean number of lesions developed in TUM (4.14±0.89) was significantly higher than in GP10 (2.05±1.02), GP50 (1.8±1.92) and GP100 (2.5±1.73) (p<0.05). The tumors formed in HEGP-treated groups were histologically more differentiated, but only in PV100 in situ lesions were evidenced. Infiltration of anatomical noble structures was less frequent in HEGP-treated groups (p<0.05). Our data suggest that oral administration of HEGP provided partial inhibition of DMBA-induced dermal carcinogenesis, as well as appeared to modulate the differentiation and infiltrative potential of the carcinomas in rodent model.

El objetivo de este estudio fue evaluar el efecto de la administración oral de extracto hidroalcohólico del propóleos verde (HEGP) sobre la carcinogénesis dérmica en modelo de roedores. Para el ensayo biológico, se utilizaron 36 ratones asignados en 6 grupos (n = 6): CTR (tratado con 100 mg/kg HEGP y sin inducción de tumores), TUM (tratada con agua e inducción de tumores), GP10 (tratado con 10 mg/kg HEGP e inducción de tumores), GP50 (tratado con 50 mg/kg HEGP e inducción de tumores) y GP100 (tratado con 100 mg/kg HEGP e inducción de tumores). La inducción de cáncer se llevó a cabo en la región dorsal de los ratones por aplicación tópica de DMBA. Después de 16 semanas, los ratones fueron sacrificados y sus dorsos fueron sometidos a análisis histológico post-mortem. El número medio de lesiones desarrolladas en TUM (4,14±0,89) fue significativamente mayor que GP10 (2,05±1,02), GP50 (1,8±1,92) y gp100 (2,5±1,73) (p<0,05). Los tumores formados en grupos tratados con HEGP fueron histológicamente más diferenciados, pero sólo en PV100 las lesiones in situ fueron manifiestas. La infiltración de las estructuras anatómicas blanco fue menos frecuente en los grupos tratados con HEGP (p<0,05). Nuestros datos sugieren que la administración oral de HEGP proporciona una inhibición parcial de la carcinogénesis dérmica inducida por DMBA, así como pareció modular la diferenciación y potencial infiltrante de los carcinomas en el modelo animal.

Modulatory effects of Azadirachta indica leaf extract on cutaneous and hepatic biochemical status during promotion phase of DMBA/TPA-induced skin tumorigenesis in mice.

The modulation in biochemical status of skin and hepatic tissue at the time point of commencement of promotion stage of skin carcinogenesis in mice and its intervention with aqueous Azadirachta indica leaf extract (AAILE) were investigated. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for 2 weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for 6 weeks on the depilated skin of mice and AAILE was administered orally at a dose level of 300 mg/kg body wt thrice a week for 10 weeks. DMBA/TPA treatment upregulated the phase I enzymes in skin and hepatic tissue, as revealed by the increased cytochrome P450 (CYP) and cytochrome b5 (cyt b5) levels and aryl hydrocarbon hydroxylase (AHH) activity when compared to the control group and differentially modulated the activities of phase II enzymes like glutathione-s-transferase (GST), DT-diaphorase (DTD) and uridine diphosphate glucuronosyltransferase (UDP-GT). AAILE treatment decreased the DMBA/TPA-induced increase in cutaneous CYP level and enhanced the DTD and UDP-GT activities when compared with DMBA/TPA group. In the hepatic tissue of AAILE + DMBA/TPA group, an increase in UDP-GT activity was observed when compared to DMBA/TPA group. DMBA/TPA treatment did not alter the skin lipid peroxidation (LPO) level when compared to control group, however, in the animals that received AAILE treatment along with DMBA/TPA, a significant increase in LPO was observed when compared to control group. This was associated with a decrease in cutaneous reduced glutathione (GSH) level of AAILE + DMBA/TPA group. Enhanced LPO level was observed in the hepatic tissue of DMBA/TPA and AAILE + DMBA/TPA groups when compared to control group. However, no alteration was observed in their hepatic GSH levels. The micronuclei score in hepatic tissue did not exhibit significant inter-group differences. The results of the present study suggest that apart from skin, liver may be affected during DMBA/TPA-induced skin tumorigenesis. AAILE treatment has the ability to modulate these changes potentially influencing the process of tumor formation. These findings seem to be important to carcinogenesis and its intervention with anti-cancer agents.

Carcinoma basoescamoso: reporte de un caso con exposición crónica a arsénico ambiental / Basosquamous carcinoma: a case report with chronic environmental arsenic exposition

Basosquamous carcinoma is a relatively rare cutaneous tumour that shares some characteristics of both basal cell and squamous cell carcinoma. Currently most dermatologists consider that it represents a subtype of basal cell carcinoma with a more aggressive behaviour. The clinical presentation is non-specific and in general the diagnosis is made after the histopathological studies. The prevalence is higher in male patients, during the seventh decade and it tends to appear on sun exposed areas. Many authors compare its behaviour with squamous cell carcinoma. We present the case of a 44 years old male patient with a history of chronic arsenic exposure that presented a firm tumor in the left inguinal region and the biopsy showed basosquamous carcinoma with lymphatic involvement. This case shows an atypical presentation because of its localization and the appearance 20 years before the mean age reported in the literature. This could be explained by chronic environmental arsenic exposure, a well known risk factor for the development of cutaneous tumours.

El carcinoma basoescamoso es una neoplasia cutánea relativamente rara que reúne características de carcinoma basocelular y espinocelular. Actualmente la mayoría de los dermatólogos reconocen que este es un subtipo del carcinoma basocelular con comportamiento muchísimo más agresivo. Su presentación clínica es inespecífica y en general su diagnóstico se realiza sólo después de la biopsia. Predomina en pacientes de sexo masculino durante la séptima década de la vida y tiende a aparecer en regiones fotoexpuestas. Muchos autores igualan su comportamiento al del carcinoma espinocelular. Se presenta el caso de un paciente, de sexo masculino, de 44 años de edad, con antecedente de exposición a arsénico medioambiental crónica, que presentó aumento de volumen, duro en la región inguinal izquierda, cuya biopsia fue compatible con carcinoma basoescamoso con compromiso linfático. El caso de nuestro paciente muestra una presentación atípica por su localización y por la aparición 20 años antes de la media de edad reportada en la literatura. Esto podría ser explicado por la exposición crónica a arsénico, conocido factor de riesgo para carcinogénesis cutánea.

Anticancer and antimutagenic properties of Acacia nilotica (Linn.) on 7,12-dimethylbenz(a)anthracene-induced skin papillomagenesis in Swiss albino mice.

We report the chemopreventive activity of Acacia nilotica (Linn.) gum, flower and leaf aqueous extracts, on 7,12-dimethylbenz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. Animals were divided into following groups: Group I (Controls) given DMBA and croton oil, with no extract ; Group II (treatment) animals treated with Acacia nilotica gum (Group II-a) (800 mg/kg body weight), flowers (Group II-b) (800 mg/kg body weight), or leaves (Group II-c) (800 mg/kg body weight) during the peri- and post initiation periods of DMBA and croton oil application. A significant reduction in the values of tumor burden, tumor incidence and cumulative number of papillomas was observed in mice treated by oral gavage with the Acacia nilotica gum, flower and leaf extracts as compared with the control group. The latency period in treatment Group-II (b) and Group-II (c) was significantly increased as compared with the control group. A significant reduction in the frequency of micronuclei was also observed in mice treated by oral gavage with the aqueous extracts, along with significant decrease in total chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, acentric fragments and exchange. Treatment with Acacia nilotica flower (Group II-B) and leaf (Group II-C) aqueous extracts by oral gavage for 15 days resulted in a highly significant decrease in the lipid peroxidation (LPO) level in the liver, but this was less evident with the gum (Group II-A) . Conversely, reduced glutathione (GSH) content was observed to be significantly elevated as compared with the control group with leaves (Group II-C) and flowers (Group II-B). The chemopreventive and antimutagenic activity of the leaf extract of Acacia nilotica was most significant followed by the flower extract and then by gum.

Involvement of multiple signaling pathways in diallyl sulfide mediated apoptosis in mouse skin tumors.

Many chemopreventive agents appear to target signaling intermediates in apoptosis-inducing pathways. Inherently, the process of neoplastic conversion selects against apoptosis to initiate, promote, and perpetuate the malignant phenotype. Thus, targeting apoptosis pathways in pre-malignant cells, in which these pathways are still relatively intact, may be an effective module of cancer prevention. Diallyl sulfide (DAS), a naturally occurring organosulfide, present in garlic, is reported to have pleiotropic biological effects. DAS is known to inhibit chemically induced tumors in a number of in vivo and in vitro studies. The aberration of tumor suppressor gene, p53 and the ras oncogene have been linked to the induction of multiple signaling pathways and to the resistance offered by cancer cells to the apoptosis. Therefore, the present study was carried out to investigate the role of DAS on modulation of multiple p53 and ras-induced signaling pathways in 7,12-dimethylbenathacene (DMBA) induced skin carcinogenesis. The results showed that DAS up regulates expression of tumor suppressor protein p53 (wt p53) and its downstream target molecule p21/waf1. Proapoptotic protein, bax was upregulated by DAS supplementation. An opposite trend was observed in DMBA induced antiapoptotic proteins expressions, survivin and bcl-2, which were significantly downregulated by DAS supplementation. In the present study we also demonstrated that DAS supplementation significantly reduces the expression of ras oncoprotein and to modulate expression of its signaling molecules including PI3K/Akt and MAPKs. Western blot analysis demonstrated that DAS significantly reduced the DMBA induced protein expressions of PI3K/Akt and p38MAPK. However, DAS supplementation did not alter the expression JNK1 and ERK1/2. Thus, our results confirm that DAS can adopt a multi-prong strategy to target multiple signaling pathways leading to induction of apoptosis and inhibition of growth of DMBA induced skin tumors in Swiss albino mice. Although studies of single pathways have been helpful in guiding investigations, new tools to study the integration and multiplicity of signaling pathways hold the hope of improved understanding of the signaling pathway alterations in cancer chemoprevention by naturally occurring compounds.

Association of arsenic-contaminated drinking-water with prevalence of skin cancer in Wisconsin's Fox River Valley.

During July 2000-January 2002, the Wisconsin Division of Public Health conducted a study in 19 rural townships. A high percentage of private drinking-water wells in these townships contained traces of arsenic. Residents were asked to collect well-water samples and complete a questionnaire regarding residential history, consumption of drinking-water, and family health. In total, 2,233 household wells were tested, and 6,669 residents, aged less than one year to 100 years, provided information on water consumption and health. The well-water arsenic levels ranged from less than 1.0 to 3,100 microg/L. The median arsenic level was 2.0 microg/L. The arsenic levels were below the federal drinking-water standard of 10 microg/L in 80% of the wells, while 11% had an arsenic level of above 20 microg/L. Of residents aged over 35 years, those who had consumed arsenic-contaminated water for at least 10 years were significantly more likely to report a history of skin cancer than others. Tobacco use was also associated with higher rates of skin cancer and appeared to synergize the effect of arsenic on the development of skin cancer.

Chemopreventive potential of Tribulus terrestris against 7,12- dimethylbenz (a) anthracene induced skin papillomagenesis in mice.

In the present investigation, the chemopreventive potential of aqueous extracts of the root and fruit of Tribulus terrestris (an Ayurvedic medicinal plant) on 7, 12 - dimethylbenz (a) anthracene (DMBA) induced papillomagenesis in male Swiss albino mice was studied. A significant reduction in tumor incidence, tumor burden and cumulative number of papillomas was observed, along with a significant increase in average latent period in mice treated orally with Tribulus terrestris suspension continuously at pre, peri and post-initiation stages of papillomagenesis as compared to the control group treated with DMBA and croton oil alone. Treatment with Tribulus terrestris suspension by oral gavage for 7 days resulted in a significant increase in the reduced glutathione content in the liver (P< 0.001 for both root and fruit extracts). Conversely, lipid peroxidation levels were significantly decreased (P< 0.001).

Modulatory influence of Rosemarinus officinalis on DMBA-induced mouse skin tumorigenesis.

The present investigation was undertaken to explore the anti-tumor promoting activity of Rosemarinus officinalis on two-stage skin carcinogenesis, induced by a single topical application of 7, 12-dimethylbenz(a)anthracene and promoted by treatment of croton oil for 15 weeks in Swiss albino mice. Oral administration of Rosemary leaf extract at a dose of 1,000 mg/ kg b. wt. / day at pre, peri and post-initiational phases, was found to be effective in decreasing the tumor incidence (50, 41.7, 58.3%, respectively) in comparison to the control (100%). Furthermore, the cumulative number of papillomas, tumor yield and tumor burden were also found to be reduced in R. officinalis-treated animals. This was associated with significant alteration in liver lipid peroxidation and glutathione (GSH) levels.

Chemopreventive action of emblica officinalis on skin carcinogenesis in mice.

Chemoprevention with food phytochemicals is currently regarded as one of the most important strategies for cancer control. Emblica officinalis (Family: Euphorbiaceae) indigenous to India, is valued for its unique tannins and flavanoids, which contain very powerful antioxidant properties. The inhibition of tumor incidences by fruit extract of this plant has been evaluated on two-stage process of skin carcinogenesis in Swiss albino mice, induced by a single application of 7, 12-dimethyabenz(a)anthrecene (100 microg / 100 microl acetone), and two weeks later, promoted by repeated application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks). The tumor incidence, tumor yield, tumor burdon and cumulative number of papillomas were found to be higher in the control (without EO treatment) as compared to experimental animals (EO treated). The differences in the values of the results of experimental groups were statistically analysed and found to be significant in comparison to the control group (p< 0.05). The present study demonstrates the chemopreventive potential of Emblica officinalis fruit extract on DMBA induced skin tumorigenesis in Swiss albino mice.

Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy.

Sarcoma de Kaposi en inmunosuprimido iatrogénico: reporte de un caso / Iatrogenic Kaposi's sarcoma in patients undergoing immunosuppresive therapy: a case report

El Sarcoma de Kaposi es una neoplasia de origen vascular que presenta cuatro formas clínicas: en ancianos de origen mediterráneo, en adultos y adolescentes en Africa, asociado a SIDA y en forma iatrogénica en pacientes inmunosuprimidos tanto por trasplante como por enfermedades autoinmunes o inflamatorias. En todos los casos se ha propuesto una relación etiológica con el virus herpes humano tipo 8; sin embargo, ésta es una condición necesaria pero no suficiente para desarrollar el tumor. En este sentido se ha planteado un posible rol directo de los corticoides como inmunosupresores. Presentamos un caso de sarcoma de Kaposi en una mujer mayor en tratamiento prolongado con corticoides y una revisión de la literatura.

Modulation of antioxidant potential in liver of mice by kernel oil of cashew nut (Anacardium occidentale) and its lack of tumour promoting ability in DMBA induced skin papillomagenesis.

Cashew nut shell oil has been reported to possess tumour promoting property. Therefore an attempt has been made to study the modulatory effect of cashew nut (Anlacardium occidentale) kernel oil on antioxidant potential in liver of Swiss albino mice and also to see whether it has tumour promoting ability like the shell oil. The animals were treated orally with two doses (50 and 100 microl/animal/day) of kernel oil of cashew nut for 10 days. The kernel oil was found to enhance the specific activities of SOD, catalase, GST, methylglyoxalase I and levels of GSH. These results suggested that cashew nut kernel oil had an ability to increase the antioxidant status of animals. The decreased level of lipid peroxidation supported this possibility. The tumour promoting property of the kernel oil was also examined and found that cashew nut kernel oil did not exhibit any solitary carcinogenic activity.

Skin cancers in chronic arsenic toxicity--a study of predictive value of some proliferative markers.

Prolonged exposure to arsenic contaminated water produces various clinical features, cutaneous features e.g. melanosis, keratosis and cancers being very common. Evaluation of such lesions by proliferative markers can provide useful information in regards to the biological behaviour of the lesions. Thus, cases with high proliferative status can be ominous sign for development of cancers. We studied skin biopsy of 42 cases. These were evaluated with AgNOR score and PCNA stain, in addition to H & E examination. Here, invasive cancer cases had mean AgNOR score of 3.56, those with severe dysplasia had 3.0, moderate and mild dysplasia scored 1.73, benign changes had mean score of 1.35 while normal control cases had 1.08. PCNA index in cancers was above 50, that of severe dysplasia 25-30, mild to moderate dysplasia 1.0-5.0, those with benign changes 0.5 -1.0 and normal control had LI of less than 0.5%. PCNA has the advantage of less chance of observer error over AgNOR stain.

Chemopreventive action of Phyllanthus urinaria Linn on DMBA-induced skin carcinogenesis in mice.

The inhibition of tumor incidence by hydro-alcoholic extract of the whole plant of P. urinaria was evaluated in 6-7 weeks old female albino mice on two-stage process of skin carcinogenesis induced by a single application of 7,12-dimethylbenz(a)anthracene (50 microg/50 microl of acetone), and 2 weeks later, promoted by repeated application of croton oil (1% in acetone/three times a week) till the end of the experiment (15 weeks). Topical application of the extract at a dose of 5 mg/kg body weight/day for 15 weeks at the peri-initiational stage (i.e., 7 days before and 7 days after DMBA application), promotional stage (i.e., from the time of croton oil application) and both peri and post-initiational stages (i.e., 7 days prior to DMBA application and continued till the end of the experiment) on the shaven backs of the mice recorded a significant reduction in tumor incidence to 50, 33.3 and 16.7% respectively in comparison to the control (i.e., the mice treated with DMBA and croton oil only) where tumor incidence was found to be 81.8%. The average number of papillomas per mouse was also significantly reduced. The results suggest a possible chemopreventive property of P. urinaria against DMBA-induced skin papillomagenesis in mice.

Chemopreventive action of Boerhaavia diffusa on DMBA-induced skin carcinogenesis in mice.

Boerhaavia diffusa, Linn (Fam: Nyctagenaceae), is widely used for the treatment of Jaundice in various parts of India. In the present study, cancer chemopreventive property of B. diffusa was evaluated on 7,12-dimethyl benz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice (6-7 weeks old). A single topical application of 7,12-dimethyl benz(a)anthracene (50 microg/50 microl of acetone), followed 2 weeks later by repeated application of croton oil (1% in acetone three times a week) and continued till the end of the experiment exhibited 100% tumor incidence. In contrast, mice treated topically on the shaven backs with the Boerhaavia diffusa extract at either the peri-initiational phase (i.e. 7 days before and 7 days after the application of DMBA; Group II), post initiational phase (i.e. from the day of start of croton oil treatment and continued till the end of the experiment; Group III) or continuously at the peri- and post-initiational stages (i.e. 7 days prior to DMBA application and continued till the end of the experiment; Group IV), a significant reduction in the values of tumor incidence (Group II - 65%; Group III - 30%; Group IV - 25%), average number of tumors per tumor bearing mouse (Group II - 2.8; Group III - 0.75; Group IV - 0.35) and papillomas per papilloma bearing mouse (Group II - 3.1; Group III - 2.5; Group IV - 1.2) were observed.