OBJECTIVE： Oleanolic acid （OA） has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular ...OBJECTIVE： Oleanolic acid （OA） has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation. METHODS： Studies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor （EGFR） activity were performed. To investigate whether cells undergo apoptosis, studies like fluorescence microscopy, poly （ADP-ribose） polymerase （PARP） degradation, annexin V-fluorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed. RESULTS： OA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells （skin keratinocytes） and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an anti- proliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondria- dependent caspase 3-mediated apoptosis. CONCLUSION： OA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent.展开更多
Background: Reviewing and analyzing the Clinico-pathologic aspects of non-melanoma skin cancer of the head and neck (NMSCHN), type of management, prognostic factors, and disease-free survival (DFS) in a period of 5 ye...Background: Reviewing and analyzing the Clinico-pathologic aspects of non-melanoma skin cancer of the head and neck (NMSCHN), type of management, prognostic factors, and disease-free survival (DFS) in a period of 5 years at the National Cancer Institute—Cairo University—Egypt. Materials and Methods: A retrospective study of two hundred patients with NMSCHN was treated at the National Cancer Institute—Cairo University—Egypt from January 2008 to December 2012. The mean follow-up was 6 months (1 - 84 months). Results: 117 males and 83 females with 90% ≥ 50 years old. The scalp (27.5%), the periorbital region (13%), the cheek (12.5%) and the nose (12.5%) are the main anatomical sites affected. BCC represented 71.5% with nodular type (79%) predominance;SCC represented 21% with GII (61.1%) the commonest grade. Surgery was the main modality of treatment (93%) with local flaps only (63.9%) and primary closure (14.7%) were the main surgical options following wide local excision. Positive and close margins were detected in 23.5% of excised specimens. No significant association was found between disease-free survival (DFS) and pathology, treatment modality, the occurrence of complications or safety margin status. Conclusion: NMSCHN lesions should be surgically excised in specialized high volume centers with readily available peripheral margin control and should be operated by senior experienced surgeons.展开更多
A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-...A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase （Cdk） 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3＇-untranslated regions （3＇UTRs） of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.展开更多
<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> There is ample evidence...<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> There is ample evidence to support the safety and efficacy of the topical anticancer cream Curaderm in the treatment of non-melanoma skin cancers. Curaderm contains the natural glycoalkaloid solamargine in the form of BEC, which has been established as a novel antineoplastic agent. BEC is the initials of the inventor of the described technology. It is known that BEC expresses anti-melanoma properties in cell culture and animals. Because of potential metastasis, clinical work with BEC on melanoma was stalled. However, recent studies show that BEC has anti-metastatic properties and this, together with currently better understanding of the mode of anti-cancer actions of BEC</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> has led to the treatment of a patient who refused to have surgery for her clinically diagnosed stage II melanoma. </span><b><span style="font-family:Verdana;">Treatment: </span></b><span style="font-family:Verdana;">A 67-year woman had a birthmark that developed into a clinically diagnosed stage II melanoma and was treated with topical application of Curaderm twice daily for 7 weeks. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> The pattern of response of the melanoma to Curaderm therapy was similar to that observed when basal cell carcinoma is treated with Curaderm. The melanoma responded rapidly to the treatment and in 7 weeks the lesion was removed with no demonstrable side effects. The cosmetic end result was very acceptable. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The clinical resolution of the melanoma with Curaderm pharmacotherapy conforms to the cell culture and animal observations that solasodine rhamnosides, and thus Curaderm, is very specific and efficacious for the first in man treatment of melanoma, creating the possibility of a simple treatment for melanoma. Further investigations with controlled clinical trials are warranted.</span></span></span></span>展开更多
In the medical field, new technologies are incorporated for the sole purpose of enhancing the quality of life for the patients and even for the normal healthy people. Infrared technology is one of the technologies tha...In the medical field, new technologies are incorporated for the sole purpose of enhancing the quality of life for the patients and even for the normal healthy people. Infrared technology is one of the technologies that have some applications in both the medical and biological fields. In this work, the thermal infrared (IR) measurement is used to investigate the potential of skin cancer detection. IR enjoys non-invasive and non-contact advantages as well as favorable cost, apparently. It is also very well developed regarding the technological and methodological aspects. IR per se is an electro-metric radiation that all objects emit when their temperature is above the absolute zero. And the human body is not different in this regard. The IR range extends, ideally, to cover wavelengths from 800 nanometer to few hundred micrometer. Cancer, in modern life, has grown tangibly due to many factors, such as life expectancies increase, personal habits and ultraviolet radiation exposures among others. Moreover, the significant enhancement of technologies has helped identifying more types of cancers than before. The sole purpose of this work is to investigate further IR technology methods and applications not yet matured in skin cancer detection to enhance the detection ability with higher safety level.展开更多
Bremachlorin®, also known as “Radachlorin®” and Photochlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution [1], was initially introduced into the Russian and South Korean Pharmac...Bremachlorin®, also known as “Radachlorin®” and Photochlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution [1], was initially introduced into the Russian and South Korean Pharmacopoeias with the corresponding marketing authorizations received in 2006 and 2008, on the basal cell skin carcinoma PDT protocol. Phase I-II clinical trials led in 2002-2005 showed no side effects, a good tolerability by patients and a high clinical anti-tumor efficacy. Further studies described in the present paper were fulfilled in accordance with a skin melanoma PDT + surgery combined technique protocol in 2006-2016. Resulting from the present trial, up to the 100% complete responses were achieved after resection and plastic surgery following PDT, with no melanoma regrowth or metastases during 5 and 10-year observation periods. Conducting PDT one day prior to tumor dissection can guarantee to meet the ablastics principles at the subsequent surgery. At the same time, the PDT + surgery protocol can allow for dissecting the tumor with less distance from its edge, which seems to be important for the face localizations of tumors.展开更多
Skin is not only a target organ for various sex steroids and hormones, but also an endocrine organ, which produces sex steroids. It has been suggested by Nikolakis et al. that impairment in skin steroidogenesis may re...Skin is not only a target organ for various sex steroids and hormones, but also an endocrine organ, which produces sex steroids. It has been suggested by Nikolakis et al. that impairment in skin steroidogenesis may result in inflammatory or autoimmune or other skin disorders. Melanoma is one such skin disease or disorder, which is believed to be caused by UV rays. But, epidemiological, clinical, in-vivo and in-vitro studies suggested the involvement of steroids in the regulation of melanoma growth. However, these studies either did not identify the steroid involved or did not relate to the protective function of the steroid in menstruating females in melanoma, as reported by the clinical studies. In this context, our studies with mouse and human melanoma cell lines showed that female sex steroid progesterone not only inhibited melanoma cell growth, but also affected adhesion and migration functions. In addition, our studies also showed that the effect of progesterone was not a toxic or spurious, but a specific effect on melanoma cells. Hence, our in-vitro studies along with previous other studies subscribed to the idea proposed earlier by Slominski et al. that modulation of local steroids could be a new therapeutic approach for treatment of skin disease or disorder, melanoma.展开更多
Controversial pigmented lesions in children are a problem for pathologist, clinicians and families that are confronted with this dilemma. Some skin lesions in this population defy diagnosis with pathologists split bet...Controversial pigmented lesions in children are a problem for pathologist, clinicians and families that are confronted with this dilemma. Some skin lesions in this population defy diagnosis with pathologists split between a benign diagnosis and a cancer diagnosis. Three cases of controversial pigmented lesions in the pediatric population are presented. Three patients underwent radical resection of the controversial pigmented lesion, intra-operative lymphatic mapping and sentinel lymph node(SLN) biopsy. Due to the low morbidity of the SLN procedure a case is made to perform lymphatic mapping in this clinical scenario. If the SLNs are negative, not much is lost except for the scar and this becomes another line of evidence that perhaps the original lesion was benign. If the SLN shows metastatic cells, then the original skin lesion must be malignant and the patient is offered stage Ⅲ recommendations that would include complete node dissections and adjuvant Interferon therapy. This strategy provides for adequate treatment of the worse-case scenario, that the skin lesion is malignant. The cost to the patient is a low morbidity procedure, the SLN biopsy.展开更多
Surgical error due to incorrect identification of the surgical site has been known to occur right from the beginning of surgical practice through the ages. However, increasing awareness, preventative efforts and risks...Surgical error due to incorrect identification of the surgical site has been known to occur right from the beginning of surgical practice through the ages. However, increasing awareness, preventative efforts and risks of litigation have not eliminated this problem. Cutaneous surgery for skin cancer makes up a large proportion of procedures performed each year and it is often difficult to correctly identify biopsy sites, especially as this is not easy in sun-damaged skin. In this review article, we review the incidence of wrong-site surgery, measures taken by professional bodies, and the use of photography and newer technologies in an attempt to eliminate this distressing event in the field of plastic and dermatologic surgery. The purpose of this review is to highlight the incidence of such surgical site identification errors, evaluate the risk factors, and educate the surgeon about measures that can be undertaken to avoid being faced with such a situation.展开更多
基金the Boiron Laboratories,Lyon,France for partial financial support of the work
文摘OBJECTIVE： Oleanolic acid （OA） has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation. METHODS： Studies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor （EGFR） activity were performed. To investigate whether cells undergo apoptosis, studies like fluorescence microscopy, poly （ADP-ribose） polymerase （PARP） degradation, annexin V-fluorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed. RESULTS： OA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells （skin keratinocytes） and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an anti- proliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondria- dependent caspase 3-mediated apoptosis. CONCLUSION： OA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent.
文摘Background: Reviewing and analyzing the Clinico-pathologic aspects of non-melanoma skin cancer of the head and neck (NMSCHN), type of management, prognostic factors, and disease-free survival (DFS) in a period of 5 years at the National Cancer Institute—Cairo University—Egypt. Materials and Methods: A retrospective study of two hundred patients with NMSCHN was treated at the National Cancer Institute—Cairo University—Egypt from January 2008 to December 2012. The mean follow-up was 6 months (1 - 84 months). Results: 117 males and 83 females with 90% ≥ 50 years old. The scalp (27.5%), the periorbital region (13%), the cheek (12.5%) and the nose (12.5%) are the main anatomical sites affected. BCC represented 71.5% with nodular type (79%) predominance;SCC represented 21% with GII (61.1%) the commonest grade. Surgery was the main modality of treatment (93%) with local flaps only (63.9%) and primary closure (14.7%) were the main surgical options following wide local excision. Positive and close margins were detected in 23.5% of excised specimens. No significant association was found between disease-free survival (DFS) and pathology, treatment modality, the occurrence of complications or safety margin status. Conclusion: NMSCHN lesions should be surgically excised in specialized high volume centers with readily available peripheral margin control and should be operated by senior experienced surgeons.
文摘A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase （Cdk） 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3＇-untranslated regions （3＇UTRs） of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.
文摘<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> There is ample evidence to support the safety and efficacy of the topical anticancer cream Curaderm in the treatment of non-melanoma skin cancers. Curaderm contains the natural glycoalkaloid solamargine in the form of BEC, which has been established as a novel antineoplastic agent. BEC is the initials of the inventor of the described technology. It is known that BEC expresses anti-melanoma properties in cell culture and animals. Because of potential metastasis, clinical work with BEC on melanoma was stalled. However, recent studies show that BEC has anti-metastatic properties and this, together with currently better understanding of the mode of anti-cancer actions of BEC</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> has led to the treatment of a patient who refused to have surgery for her clinically diagnosed stage II melanoma. </span><b><span style="font-family:Verdana;">Treatment: </span></b><span style="font-family:Verdana;">A 67-year woman had a birthmark that developed into a clinically diagnosed stage II melanoma and was treated with topical application of Curaderm twice daily for 7 weeks. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> The pattern of response of the melanoma to Curaderm therapy was similar to that observed when basal cell carcinoma is treated with Curaderm. The melanoma responded rapidly to the treatment and in 7 weeks the lesion was removed with no demonstrable side effects. The cosmetic end result was very acceptable. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> The clinical resolution of the melanoma with Curaderm pharmacotherapy conforms to the cell culture and animal observations that solasodine rhamnosides, and thus Curaderm, is very specific and efficacious for the first in man treatment of melanoma, creating the possibility of a simple treatment for melanoma. Further investigations with controlled clinical trials are warranted.</span></span></span></span>
文摘In the medical field, new technologies are incorporated for the sole purpose of enhancing the quality of life for the patients and even for the normal healthy people. Infrared technology is one of the technologies that have some applications in both the medical and biological fields. In this work, the thermal infrared (IR) measurement is used to investigate the potential of skin cancer detection. IR enjoys non-invasive and non-contact advantages as well as favorable cost, apparently. It is also very well developed regarding the technological and methodological aspects. IR per se is an electro-metric radiation that all objects emit when their temperature is above the absolute zero. And the human body is not different in this regard. The IR range extends, ideally, to cover wavelengths from 800 nanometer to few hundred micrometer. Cancer, in modern life, has grown tangibly due to many factors, such as life expectancies increase, personal habits and ultraviolet radiation exposures among others. Moreover, the significant enhancement of technologies has helped identifying more types of cancers than before. The sole purpose of this work is to investigate further IR technology methods and applications not yet matured in skin cancer detection to enhance the detection ability with higher safety level.
文摘Bremachlorin®, also known as “Radachlorin®” and Photochlorin, a composition of 3 chlorophyll a derivatives in an aqueous solution [1], was initially introduced into the Russian and South Korean Pharmacopoeias with the corresponding marketing authorizations received in 2006 and 2008, on the basal cell skin carcinoma PDT protocol. Phase I-II clinical trials led in 2002-2005 showed no side effects, a good tolerability by patients and a high clinical anti-tumor efficacy. Further studies described in the present paper were fulfilled in accordance with a skin melanoma PDT + surgery combined technique protocol in 2006-2016. Resulting from the present trial, up to the 100% complete responses were achieved after resection and plastic surgery following PDT, with no melanoma regrowth or metastases during 5 and 10-year observation periods. Conducting PDT one day prior to tumor dissection can guarantee to meet the ablastics principles at the subsequent surgery. At the same time, the PDT + surgery protocol can allow for dissecting the tumor with less distance from its edge, which seems to be important for the face localizations of tumors.
文摘Skin is not only a target organ for various sex steroids and hormones, but also an endocrine organ, which produces sex steroids. It has been suggested by Nikolakis et al. that impairment in skin steroidogenesis may result in inflammatory or autoimmune or other skin disorders. Melanoma is one such skin disease or disorder, which is believed to be caused by UV rays. But, epidemiological, clinical, in-vivo and in-vitro studies suggested the involvement of steroids in the regulation of melanoma growth. However, these studies either did not identify the steroid involved or did not relate to the protective function of the steroid in menstruating females in melanoma, as reported by the clinical studies. In this context, our studies with mouse and human melanoma cell lines showed that female sex steroid progesterone not only inhibited melanoma cell growth, but also affected adhesion and migration functions. In addition, our studies also showed that the effect of progesterone was not a toxic or spurious, but a specific effect on melanoma cells. Hence, our in-vitro studies along with previous other studies subscribed to the idea proposed earlier by Slominski et al. that modulation of local steroids could be a new therapeutic approach for treatment of skin disease or disorder, melanoma.
文摘Controversial pigmented lesions in children are a problem for pathologist, clinicians and families that are confronted with this dilemma. Some skin lesions in this population defy diagnosis with pathologists split between a benign diagnosis and a cancer diagnosis. Three cases of controversial pigmented lesions in the pediatric population are presented. Three patients underwent radical resection of the controversial pigmented lesion, intra-operative lymphatic mapping and sentinel lymph node(SLN) biopsy. Due to the low morbidity of the SLN procedure a case is made to perform lymphatic mapping in this clinical scenario. If the SLNs are negative, not much is lost except for the scar and this becomes another line of evidence that perhaps the original lesion was benign. If the SLN shows metastatic cells, then the original skin lesion must be malignant and the patient is offered stage Ⅲ recommendations that would include complete node dissections and adjuvant Interferon therapy. This strategy provides for adequate treatment of the worse-case scenario, that the skin lesion is malignant. The cost to the patient is a low morbidity procedure, the SLN biopsy.
文摘Surgical error due to incorrect identification of the surgical site has been known to occur right from the beginning of surgical practice through the ages. However, increasing awareness, preventative efforts and risks of litigation have not eliminated this problem. Cutaneous surgery for skin cancer makes up a large proportion of procedures performed each year and it is often difficult to correctly identify biopsy sites, especially as this is not easy in sun-damaged skin. In this review article, we review the incidence of wrong-site surgery, measures taken by professional bodies, and the use of photography and newer technologies in an attempt to eliminate this distressing event in the field of plastic and dermatologic surgery. The purpose of this review is to highlight the incidence of such surgical site identification errors, evaluate the risk factors, and educate the surgeon about measures that can be undertaken to avoid being faced with such a situation.
