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Birth defects is one of the most important problems of human society. External birth defect is one of the major research fields of plastic surgery. This kind of disorders damages the body image of patients in mild or severe way, affects severely the social confidence of the patients themselves and their families. we summarized the research progress of the common external birth defects (the incidence top 10) from the aspects of pathogenesis, prevention, treatments and so on, in order to provide reference materials to the prevention and treatment of them.
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The facial artery perforator flap has the advantages of minimal donor site morbidity, acceptable appearance and function at recipent area, which brings its wide application in reconstruction of facial small and medium-sized defects. Nasal defects, as the most important aesthetic unit at face, require three-dimennsional and precise reconstruction. The article reviewed the anatomic study and the current status of the clinical applications of this technique in reconstruction of nasal defects, as well as the existing questions. The prospective application of SPY system in localization of facial artery perforator was also analyzed.
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Objective@#To explore the clinical effects of scapular region flaps pedicled with circumflex scapular artery in the reconstruction of axillary burn scar contractures.@*Methods@#From December 2008 to December 2018, 21 patients with axillary burn scar contractures were admitted to our department. There were 12 male patients and 9 female patients, aged 2-48 years, with an average of 17.4 years. According to the characteristics of axillary scar contractures, the patients were divided into type Ⅰ of 5 patients, type Ⅱ of 2 patients, type Ⅲ of 5 patients, and type Ⅳ of 9 patients. The preoperative abduction ranges of shoulder joint were 20-150°, with an average of 68.33°. The wound areas after resection and release of scar contractures ranged from 12 cm×4 cm to 33 cm×11 cm, with an average of 18.13 cm×5.41 cm, and the wounds were repaired with scapular region flaps pedicled with circumflex scapular artery in the areas of 14 cm×5 cm-35 cm×14 cm, with an average of 20.19 cm×7.71 cm. The donor sites of 5 patients were expanded prior to flap repair operation, and the other 16 patients were repaired by direct transfer of flaps. The donor sites were closed directly. The type, number, and transfer way of scapular region flaps were calculated, and the improvement of abduction angle of shoulder joint and condition of the flaps were observed during follow-up after operation.@*Results@#There were 5 ascending scapular flaps, 13 scapular flaps, and 3 parascapular flaps. The flaps were transferred through open wounds in 18 cases, subcutaneous tunnel in 1 case, and trilateral foramia in the remaining 2 cases. All the flaps survived after operation. During follow-up of 3 months to 5 years, with an average of 19.4 months, the abduction angles of shoulder joints were 90-180°, with an average of 137.62°, which showed that the abduction function of shoulder joint improved obviously. The texture of flap was soft, and the color of the flap was close to the surrounding skin. The patients and/or their family members were satisfied with the operation results.@*Conclusions@#The scapular region flap pedicled with circumflex scapular artery has a lot of advantages, including a long vascular pedicle, simple technique for flap harvest, a hidden donor site, and flexible and diverse transfer mode of flap. It is an effective option for clinical reconstruction of severe axillary burn scar contracture.
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Objective@#This is a study to evaluate complication rate, satisfaction and quality of life after breast reconstruction under different classifications. The classification criteria are the timing of operation, surgical procedures, and patients′age.@*Methods@#By reviewing the surgical cases from August 2004 to June 2018, the authors summarized the data of 102 patients with breast reconstruction of the same surgeon in Peking University People′s Hospital and Plastic Surgery Hospital (Institute) CAMS PUMC. Fifty-four patients who met the inclusion criteria and completed the BREAST-Q breast reconstruction module scale, were divided into immediate group or delayed group, according to the timing of operation; divided into abdomen group or other procedures group, according to the surgical procedure; and divided into the young patients′group or senior patients′group according to age. The index were (1) postoperative complication rate, (2)satisfaction with breasts, psychosocial well-being, physical well-being of chest and abdomen, sexual well-being, satisfaction with outcome, satisfaction with information, satisfaction with care (based on the BREAST-Q scale).@*Results@#Complication rate was 9.1%(1/11) in the immediate group, 16.3%(7/43) in the delayed group, 14.7%(5/34) in the abdomen group, 15.0%(3/20) in other procedures group, 13.6%(3/22) in the young patients′group, and 15.6%(5/32) in the senior patients′group. There was no significant difference in the incidence of complications (P>0.05). The postoperative scores of satisfaction with breasts, psychological well-being and sexual well-being were significantly higher in the immediate group than in the delayed group(P=0.026, P<0.001 and P=0.001, respectively). The score of postoperative physical well-being of chest was significantly higher in the abdomen group than other procedures group(P=0.020). The score physical well-being of abdomen was lower compared with the preoperative in the abdomen group (P<0.001). The score of physical well-being of abdomen was lower in the senior patients′group than that of the young patients′group (P=0.010).@*Conclusions@#The complication incidence of breast reconstruction patients was similar among different groups. The breast reconstruction surgery can significantly improve satisfaction and quality of life of patients. To some extent, immediate breast reconstruction can reduce the psychological and physiological effects of breast loss on patients, leading to higher postoperative satisfaction. Breast reconstruction with abdominal flaps can provide patients with better chest health but poor abdomen health. Although elderly patients undergoing breast reconstruction will have poor physical well-being of abdomen, they can still achieve higher satisfaction of operation.
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Objective@#To investigate the distribution of the septocutaneous perforators in the medial arm and its clinical applications.@*Methods@#Between March 2014 and August 2018, 39 patients (45 arms) were included in the study. A coordinate system originating at the medial epicondyle was established, with the y-axis running to the axillary apex and expressed in relative value. The y-axis was trisected and each third from proximal to distal were designated as A, B, and C, respectively. Based on this, the medial arm flap was used to reconstruct defects in the head and neck, hand, axilla, elbow and chest wall.@*Results@#An average of 4.6 perforators were identified along the medial intermuscular septum of the arm, located at 0.87±0.08, 0.50±0.09 and 0.20±0.06 on the y-axis, with a prevalence of 95.6%, 100% and 86.7%, respectively. Among the 45 flaps, 30 were used as pedicled distant flaps and 15 as perforator-based propeller flaps, with an average size of 18.7 cm×8.1 cm. The average length of the perforator pedicle was 3.1 cm. One pedicled distant flap developed hematoma after pedicle division but recovered with hematoma removal. One perforator-based propeller flap had partial loss of the distal third, requiring surgical debridement followed by a local flap transfer. Two perforator-based propeller flaps had venous congestion but survived completely with conservative therapy. The remaining flaps healed uneventfully. Donor-site morbidity was minimal. The patients were followed up for 6 months to 3 years (average 12.6 months) with satisfactory aesthetic appearance, greatly improved function and no tumor recurrence.@*Conclusions@#The constant perforators could be found in each third of the medial arm. The perforator-based medial arm flap could be used for various soft-tissue defect reconstructions.
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Objective@#To investigate the efficacy and the technical details of utilizing a long segment of vein graft to bridge the vascular defect when a free flap is used to repair extensive injuries in lower extremities.@*Methods@#For the reconstruction of extensive leg defect caused by serious composite injury, a local flap is unavailable or cannot fulfill the requirements. The main vessels of the leg could be damaged. It is challenging work to find an ideal recipient vessels for a free flap. The saphenous vein was harvested from the contralateral lower extremities and utilized to bridge the vascular gap between the recipient vessels and flap pedicle vessels. A latissimus dorsi myocutaneous or anterolateral thigh free flap was used to reconstruct the leg defect. The distal end of the grafted vein was anastomosed to the superficial femoral artery in an end-to-side fashion, and the proximal end to the artery of flap pedicle in an end-to-end fashion. When a vein insufficiency was present, the proximal and distal ends of the additional grafted vein were anastomosed to the recipient vein and vein of flap pedicle in an end-to-end fashion.@*Results@#From July 2010 to April 2019, 27 patients underwent reconstruction of leg using the above-mentioned method. There were 20 males and 7 females. The patients′ age ranged from 16 to 54 years with an average of 30.6 years. There were 19 latissimus dorsi myocutaneous flaps and eight anterolateral thigh flaps. The grafted saphenous vein was used to bridge the arterial gap in 21 cases and to bridge both the arterial and venous gaps in 6 cases. The length of the grafted vein for arterial and venous defects was ranged from 14 cm to 43 cm (mean, 24.8 cm) and 5 cm to 12 cm (mean, 8.6 cm), respectively. 26 flaps completely survived after surgery. Venous congestion occurred in the remaining one flap and the flap eventually lost. The patient eventually opted for amputation. All patients were followed up for 3 to 14 months with an average of 9 months. Functional and aesthetic outcomes were obtained in both the recipient and donor sites. No obvious edema of lower extremities was observed.@*Conclusions@#For patients with a severe and large soft-tissue defect of the leg, fining an ideal recipient vessels for a free flap is crucial for a successful reconstructive surgery. It is a reliable and an additional option to choose the superficial femoral artery and/ or saphenous vein as the recipient vessels by using the grafted vein to bridge the vascular gaps.
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Objective@#To explore the flap design and clinical applications of the propeller flaps based on perforators from different branches of the lateral circumflex femoral artery in defect reconstruction.@*Methods@#Between September 2009 and December 2018, 27 patients with soft tissue defects from lower extremities were involved in this study, including 15 males and 12 females, with an average age of 34.6 years old (range, 3 to 73 years old). Before surgery, the type of the flap to be used was designed preliminarily by evaluating the location, size and shape of the lesion or defect. The perforators of the lateral circumflex femoral artery were explored using an ultrasound Doppler probe, marked on skin. The computed tomographic angiography was also used to get more information of the branches of the lateral circumflex femoral artery when possible. The propeller flaps were divided into typeⅠ, Ⅱ, Ⅲ, and Ⅳ according to the perforators that originated from the transverse, descending, oblique, and rectus femoris branches of the lateral circumflex femoral artery, respectively. The type Ⅱ flap was subdivided into type Ⅱa and type Ⅱb flaps that were based on antegrade and reverse flow from the descending branch. The defects were reconstructed using the perforator propeller flap.@*Results@#Twenty-seven patients underwent reconstruction of defects using the propeller flaps based on perforators from different branches of the lateral circumflex femoral artery including 3 type Ⅰ flap, 12 type Ⅱa, 2 type Ⅱb, 10 type Ⅲ and 3 type Ⅳ. The size, pedicle length and rotation angle of the flaps were 12 cm×6 cm to 30 cm×15 cm, 4 cm to 15 cm, and 60 to 180 degrees, respectively. Total necrosis occurred in one flap and small-sized distal necrosis in another one. Minor complications occurred in two flaps and the remaining propeller flaps survived completely. All patients were followed up from one to 25 months and mean follow-up time was 9.9 months. Tumor recurrence was noticed in one patient. All patients were satisfied with the final functional and aesthetic outcomes.@*Conclusions@#For appropriate cases, reconstruction of defects from the groin to the knee could be achieved by using the propeller flaps based on perforators from different branches of the lateral circumflex femoral artery, with advantages of easy-to-operate and minor donor-site morbidity.
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The authors reviewed the concepts of the axial pattern flap, angiosome and perforasome, and analyzed the anastomosis and hemodynamic characteristics between the angiosome and the perforasome. Results: (1) Axial pattern flaps can be designed either in the angiosome or in perforasome. The difference is the pedicle and vascular axis. (2) The middle perforator should be the first choice as the pedicle for multi-perforators cross-territory flap, and the axial direction of the flap should be the same as that of the source artery. (3) Avoid as much as possible nutrient large flap with small blood vessels, that is, using a perforating vessel as a pedicle to cross-zone support to an angiosome flap. (4) The position of vascular pedicle and venous drainage is more important than the size and number of blood vessels. It is proposed that the transformation and reconstruction of the axial vascular in the multi-perforated cross zone flap to establish a new blood circulation system is a research hotspot and challenges in the study of anatomy. It is necessary to work closely with the surgeons.
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A large number of innovative and new technologies and method in the field of perforator flap were proposed with the hard work of many experts and surgeons. This paper briefly reviewed the following items including the discovery of the perforator flap and its enlightenment to us, three-dimensional visualized anatomy, angiosome and perforasome theories, pre-operative perforator detection techniques, techniques for evaluation of the flap vascular perfusion, the concept of freestyle perforator flap, chimeric flap, flow-through flap technique, new designs of pedicle perforator flap, particularly the propeller and keystone flaps, supramicrosurgery, superthin flap, microdissected thin perforator flap, and microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. These new technologies and method have greatly improved our understanding of flap surgery and promote the development of the reconstructive surgery. The traditional research focused on investigating the anatomic features of a single flap and strategies for the reconstruction of different defects and organs. Nowadays, the treatment scope of reconstructive surgery is more extensive and has developed to repair various refractory wounds following trauma and oncological resection, nerve injuries, and to reconstruct defect and organ by using the vascularized composite allotransplantation. Researches on the upper limb lymphedema after breast cancer surgery have been highly valued recently. It can be expected that the direction of reconstructive surgery would be transformed from the improvement of theraputic modalities to concentrating on the treatment of diseases, and this undoubtedly conforms to the essence of medicine. The research of perforator flaps will be directed to more precise, minimally invasive, and individualized according to the requirements of evidence-based medicine.
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A 37-year-old woman presented with a congenital spinal meningocele for 37 years and ruptured for 6 months. She was admitted to the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences in March 2018. The diameter of the lesion was about 10 cm, with purulent secretion and malodor. The superior gluteal artery perforator propeller flap was used to reconstruct the defect after the lesion resection. Part of the wound didn’t heal and cerebrospinal fluid leaked from the wound postoperatively. The wound eventually healed after wound debridement and drainage changing. Cerebrospinal fluid retention under the flap could result in wound dehiscence and cerebrospinal fluid leakage. The author introduced the treatment process and operative method. The preliminary experience in treating cerebrospinal fluid leakage after surgical management of the spinal meningocele was also summarized.
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Objective@#To explore the feasibility and technical points of soft tissue defect reconstruction using the pedicled anterolateral thigh flap based on perforating vessels from the lateral circumflex femoral artery oblique branch.@*Methods@#Between November 2009 and April 2019, 27 pedicled anterolateral thigh flaps were performed to repair the wound of trunk and lower extremity, based on perforating vessels from the lateral circumflex femoral artery oblique branch. 16 flaps were proximally based and 11 were distally based.@*Results@#The proximally based flap ranged from 15 cm×8 cm to 32 cm×12 cm. The mean length of the pedicle was 8.2 cm. The distally based flap ranged from 9 cm×7 cm to 24 cm×8 cm. The mean length of the pedicle was 18.6 cm. All flaps survived after surgery. Venous congestion occurred in one flap and relieved in five days.@*Conclusions@#With oblique branch as the pedicle, the vascular dissection was easy and donor site morbidity was minimized while harvesting the proximally based anterolateral thigh flaps; long pedicle could be obtained, and the reconstructive sphere was extended when using the distally based anterolateral thigh flaps.
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Objective Toanalyzetheimagingfeaturesofmedulloepitheliomaforfurtherunderstanding.Methods Theimaging findingsof12casesofmedulloepitheliomaprovedbypathologywereanalyzedretrospectively.Results Thelesionswerelocatedin cerebralhemisphere(6),cerebellum (3),ventricularsystem (3),andalloftheminvolvedbothgrayandwhitematter.Thefeatures includedlargegrosstumorvolume,clearboundaryandperitumoraledema(8/12).Othersincludedcystic-solidlesions(11/12),completelysolidlesion (1/12),andiso-orslightlyhyper-densitywithcalcificationonCTscan.ThetypicalfeatureofMRIwas "mid-lakeisland"sign,and solidcomponentshowediso-orhypo-intensityonT1WI,isoorhyper-intensityonT2WIwithhemorrhageandnecrosis,aswellasthe tumorshowedobviousheterogeneousenhancementaftercontrast.Cystcomponentshowedthin-wallring-enhancement.Conclusion Thetypicalfeatureofthemedulloepitheliomaisthe "mid-lakeisland"sign.Thetumorhasalargevolume,andthe majorityshow cystic-solidlesions.Aboveall,medulloepitheliomashouldbeconsideredifthereisasolid-cysticlesionwithclearboundaryatchildren andadolescents.
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Objective@#To propose a classification method and explore the indications and technical tips of the pedicled deep inferior epigastric artery perforator (DIEAP) flap.@*Methods@#From July 2005 to December 2017, 18 patients underwent soft-tissue defect repairment using the pedicled DIEAP flap. The defect locations included abdomen (n=6), iliolumbar region (n=2), perineum (n=4), and proximal thigh (n=6). The flaps were divided into two types. The type Ⅰ flap were further subdivided into two subtypes. The type Ⅰa flap was solely based on the DIEAP. The type Ⅰb flap was also based on the DIEAP, however, the main trunk of the deep inferior epigastric vessels needs to be divided to further improve the pedicle length. The type Ⅱ flap was the traditional pedicled DIEAP flap.@*Results@#Twenty flaps were included in this series. The mean flap size and pedicle length of the 4 flaps in type Ⅰa were 19.0 cm× 6.5 cm and 2.88 cm respectively. The rotation angles were 60 degrees (n=1), 120 degrees (n=1), and 180 degrees (n=2). The 3 flaps of type Ⅰb was 26 cm × 6 cm, 20 cm × 5 cm and 24 cm × 7 cm in size, and the pedicle lengths of them were 6 cm, 7 cm and 7 cm, respectively. All flaps in this subtype were rotated by 180 degrees. The mean flap size and pedicle length of the 13 type Ⅱ flaps were 21.46 cm × 9.38 cm and 11.08 cm. 17 flaps completely survived postoperatively. Small-sized necrosis of the distal portion of the flap occurred in 3 flaps. All patients were followed up for 6 months to 5 years, with the averaged 11 months follow-up time. All patients were satisfied with the final outcomes. Tumor recurrence was not noticed for the oncological patients.@*Conclusions@#The pedicled DIEAP flap has remarkable versatility in the defect repairment for the regions including abdomen, iliolumbar region, proximal thigh, and perineal region. Combining with the " propeller flap" concept, the clinical application of pedicled DIEAP flap could be further expanded. The pedicled DIEAP flap is a reliable reconstructive method for defect repairment in abdominal and iliolumbar regions.
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Based on literature review and comparative studies, the most useful anatomical method that were convenient for both medical researchers and surgeons were introduced. Practical examples were used to illustrate how to gather and rectify the information of the perforating vessels and to design a perforator flap. In addition, the survival mechanisms of cross-territory perforator flap and modalities that can be used to promote the flap survival were also reviewed. Previous research showed: ①The position, diameter, pedicle length, axiality, and vascular territory of a specific perforator were important parameters for observation. ②The traditional cadaveric study and the X-ray examination of post-perfusion cadaveric specimens could provide two-dimensional information about the perforating vessels. CT angiography could provide more accurate information of the perforators. Adjacent structures could be clearly revealed when the data of CT angiography was dealt with the MIMICS software. ③The survival of the cross-territory perforator flap could be enhanced by various different maneuvers. How to reconstruct the new blood circulation system in the multi perforator cross zone flap is a research hotspot and challenges in the study of anatomy. It is necessary to work closely with the surgeons.
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Objective@#To explore the feasibility and technical tips of defect reconstruction using the pre-expanded perforator propeller (PEPP) flap.@*Methods@#From July 2009 to December 2017, 56 patients underwent defect reconstruction using the PEPP flap. During the first-stage operation, an expander with appropriate size was buried within a soft-tissue pocket. Three strategies were used for expander placement, including placement of the expander underneath the muscle, at a distance from the emergence point of the perforator when the perforator location is relatively fixed, and following the criteria when a free-style perforator flap is designed. At the second-stage operation, a PEPP flap was raised and rotated a certain number of degrees to reconstruct the defect.@*Results@#56 flaps were elevated. The expanders were buried according to the strategy Ⅰ in 2 cases, the strategy Ⅱ in 42 cases, and the strategy Ⅲ in 12 cases. The flap size ranged from 7-13 cm to 14-32 cm with the average size of 9.38 cm × 21.22 cm. The pedicle length ranged from 2.5 cm to 10 cm and the mean length was 5.03 cm. The rotation angle was 180 degrees in 44 cases, 150 and 120 degrees in 6 cases respectively. The perforators that were previously explored were all identified during the second-stage operation. 53 flaps survived completely. Venous congestion of the distal portion of the flap was observed after the surgery in two cases. Necrosis of small area of the flap occurred and free skin grafting was used to resurface the defect after debridement. All patients were followed up for 3 months to 4 years and the average follow-up time was 13.4 months.@*Conclusions@#The PEPP flap can not only ensure primary closure of the donor site, but also provide more extra tissue for defect reconstruction. For selected patients, it could be an alternative option for soft-tissue defect reconstruction.
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Objective@#To investigate the feasibility and technical tips of repairing facial defects with pre-expanded propeller flap based on the perforators of the supratrochlear artery or the supraorbital artery.@*Methods@#In the first-stage operation, a tissue expander was buried underneath the frontalis muscle. The second-stage operation was conducted using pre-expanded supratrochlear artery or the supraorbital artery based propeller flap to repair facial defect.@*Results@#From July 2010 to July 2016, this method was used in 8 patients. 5 flaps were based on the supratrochlear artery, and 3 flaps based on the supraorbital artery. Expander size was ranged from 150 ml to 300 ml. The size of propeller flaps was from 10 cm × 6 cm to 15 cm × 13 cm. All the flaps survived without any major complications. Follow-up period ranged from 3 to 36 months. Eyebrow replacement, flap thinning and scar revision were performed in 6 cases. All patients were satisfied with the final aesthetic result.@*Conclusions@#The pre-expanded propeller flap based on the supratrochlear artery or the supraorbital artery is an alternative option to repair the facial defect in appropriate cases.
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Since the first description by Koshima in 1989, perforator flaps have become one of the most commonly used tools for soft tissue defects and organ reconstruction.The three period history of perforator flaps was briefly reviewed.In the first period(from 1989-2000), pioneers persisted in studying perforator flaps and did outstanding work to define and develop the new technique.In the second period(from 2000-2010), the idea of perforator flaps is widely accepted.Moreover, in the third period(from 2010-present), the application of perforator flaps was extended to new medical fields, and reconstruction surgeons began reporting their clinical experiences.As an important historical event, the "Gent" consensus on perforator flaps terminology was introduced in detail.The existing definition, classification, terminology, and nomenclature of perforator flaps were reviewed.Some of the most frequently used perforator flaps are briefly described.Surgeons that popularized the use of perforator flaps were reviewed as well as the inspiration drawn from the 30 year fascinating historical evolution of perforator flaps.
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Objective To investigate the effect of epidermal growth factor (EGF) on the proliferation of endometrial adenocarcinoma cells,phosphorylation of estrogen receptor α (ERα)and Ack1 in the absence of estrogen.MethodsIshikawa cell line was stimulated by EGF without estrogen settings, Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation, Western blot was used to detect ER α phosphorylation and Ack1 phosphorylation.Giving tyrosine inhibitor dasatinib to assess the effect of EGF on cell proliferation,phosphorylation of ERα and Ack1 in Ishikawa cells.Results EGF enhanced the proliferation of endometrial adenocarcinoma cells (P<0.05).EGF induced ERα phosphorylation at Tyr-537 and phosphorylation of Ack1.Compared with untreated control, Dasatinib inhibited the proliferation of endometrial adenocarcinoma cells (P<0.05), phosphorylation of ERα Tyr-537 and Ack1.Conclusions EGF promotes Ishikawa cells proliferation in the possible way of activating ER α site-specific phosphorylation at Tyr-537 and phosphorylation Ack1, which could be blocked by dasatinib.
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Objective@#To evaluate the efficacy of indocyanine green SPY imaging in flap surgery.@*Methods@#Between July 2016 and March 2017, forty-five flaps of thirty-five consecutive patients were retrospectively analyzed, among which forty-four were pedicled flaps and one was free flap, measuring from 2.0 cm×1.5 cm to 34.0 cm×17.0 cm. SPY imaging was performed twice for each flap, after the elevation of flap and after flap insertion respectively. The correlation of the flap perfusion detected by SPY and the prognosis of each flap were recorded and analyzed.@*Results@#Twenty-nine flaps demonstrated good perfusion on SPY healed uneventfully. Sixteen flaps were demonstrated poor perfusion in the distal part of flap. Two flaps underwent surgical intervention intraoperatively and totally survived. Fourteen flaps were preserved conservatively and nine suffered partial- or full-thickness necrosis. None of the remaining five flaps sustained necrosis. Secondary healing was achieved through regular dressing change or operative debridement. The sensitivity, specificity and accuracy were 100%(9/9), 85.3%(29/34) and 88.4%(38/43) respectively.@*Conclusions@#Intraoperative indocyanine green SPY imaging is a useful adjuvant to evaluate flap perfusion and predict necrosis in plastic surgery, enhancing a surgeon’s clinical judgment of flap viability.
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Objective To investigate the mechanism of dasatinib,tyrosine kinase inhibitor,inhibiting androgen receptor (AR) phosphorylation in prostate cancer cells.Methods HEK-293T and COS7 cell lines were cotransfected by wild-type (WT)-AR,ARY267F or ARY534F with Ack1 or Src,respectively,and Western blot was used to detect the AR phosphorylation sites.LNCaP cells were treated by EGF or heregulin without androgen,then Western blot was used to detect AR phosphorylation.After these LNCaP cells were treated by dasatinib or transfection with siRNA to silence Ack1 or Src gene,Western blot was used to observe the effect on AR phosphorylation,and quantitative real-time reverse transcription polymerase chain (RT-PCR)was applied to detect PSA mRNA and hk2 mRNA.Results After transfection,Ack1 kinase mediated the phosphorylation of AR Tyr267 in HEK-293T cells,and Src mediated AR Tyr534 phosphorylation in COS7cells.When LNCaP cells were treated by heregulin,AR Tyr267 was phosphorylated,but its phosphorylation was inhibited after these cells were treated by dasatinib or ack1 gene was silenced.When LNCaP cells were treated by EGF,AR Tyr534 was phosphorylated,but its phosphorylation was inhibited after these cells were treated by dasatinib or Src gene was silenced.EGF or heregulin raised endogenous AR target gene,PSA and hK2,mRNA levels in LNCaP cells (P ＜ 0.05).However,after these cells were treated by dasatinib,PSA and hK2 mRNA levels induced by heregulin were decreased (P ＜ 0.05),but those induced by EGF PSA were no significant changes (P ＞ 0.05).Conclusion Dasatinib can inhibit AR Tyr267 and AR Tyr 534phosphorylation,and it may play a significant role in anti-prostate cancer cells by inhibiting Ack1-mediated AR Tyr-267 phosphorylation and the expression of PSA mRNA and hk2 mRNA induced by heregulin.