Growth factors and wound healing in the hamster

We have investigated the effect of topically applied mitogenic preparations on the healing of full-thickness skin wounds in the Syrian hamster. In an attempt to accelerate the healing process, dexamethasone and insulin, platelet-derived growth factor, fibroblast growth factor, thrombin, defined medium F for fibroblasts, liver cell supernatant, epidermal growth factor, and colostrum were applied to the wounds. These mitogens had no significant influence on the rate of wound contraction or on the time to complete healing in full-thickness, noncompromised skin wounds in this animal model.     

Delayed skin grafting

The use of skin grafts on granulating wounds is an established practice. Delaying the application of a full- or split-thickness skin graft may be an advantageous alternative method of surgical reconstruction in selected cases. Partial healing by secondary intention is useful for filling in deeper defects and usually produces a wound that is much smaller and of more normal contour than the original defect. Contraction of the graft bed is markedly influenced by location, tissue laxity, surface tension lines, motion, and wound geometry. Proper wound care, correct surgical preparation of the defect, and timing of the graft procedure are all important considerations in maximizing the overall result. Through-and-through defects and wounds produced over areas with little underlying support (eyelids and lip) often need flap reconstruction or immediate grafting to prevent undesirable functional and cosmetic results. By combining delayed healing and conventional reconstructive techniques, major tissue loss can often be restored while minimizing patient morbidity.     

Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers.

A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds. In this pilot double-blind randomized study conducted at a single center, we used human recombinant epidermal growth factor (h-EGF) to treat 44 patients with venous ulceration of the lower extremities. An aqueous solution (10 micrograms/mL) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks. Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting. Nine patients were excluded from efficacy evaluation because of protocol violations. Therefore, 35 patients (17 h-EGF, 18 placebo) were evaluable for efficacy, and 44 patients (22 h-EGF, 22 placebo) were available for safety. The median baseline ulcer size for all patients was 18.5 cm2, and was not significantly different between h-EGF and placebo group (12.9 cm2 versus 19.2 cm2, respectively, P = .27). By study end, six (35%) of h-EGF treated patients and two (11%) in the placebo group had healed completely (P = .10). Another 6 patients (2 of 17 h-EGF, 4 of 18 placebo; P = .50) developed healthy granulation tissue that was suitable for grafting. The median ulcer size reduction was 7% for h-EGF versus 3% for placebo per week (P = .29), and 73% versus 33% at study end (P = .32). No untoward side effects were related to the application of h-EGF. We conclude that topical application of h-EGF, in the dose and manner used in this study, was safe but failed to significantly enhance re-epithelialization of venous ulcers. However, a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results.     

Loss of vascular endothelial growth factor a activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation

The angiogenic cytokine vascular endothelial growth factor (VEGF)-A plays a central role in both wound healing and tumor growth. In the skin, epidermal keratinocytes are a major source of this growth factor. To study the contribution of keratinocyte-derived VEGF-A to these angiogenesis-dependent processes, we generated mice in which this cytokine was inactivated specifically in keratin 5-expressing tissues. The mutant mice were macroscopically normal, and the skin capillary system was well established, demonstrating that keratinocyte-derived VEGF-A is not essential for angiogenesis in the skin during embryonic development. However, healing of full-thickness wounds in adult animals was appreciably delayed compared with controls, with retarded crust shedding and the appearance of a blood vessel-free zone underneath the newly formed epidermis. When 9,12-dimethyl 1,2-benzanthracene was applied as both tumor initiator and promoter, a total of 143 papillomas developed in 20 of 23 (87%) of control mice. In contrast, only three papillomas arose in 2 of 17 (12%) of the mutant mice, whereas the rest merely displayed epidermal thickening and parakeratosis. Mutant mice also developed only 2 squamous cell carcinomas, whereas 11 carcinomas were found in seven of the control animals. These data demonstrate that whereas keratinocyte-derived VEGF-A is dispensable for skin vascularization under physiological conditions, it plays an important albeit nonessential role during epidermal wound healing and is crucial for the development of 9,12-dimethyl 1,2-benzanthracene-induced epithelial skin tumors.     

The effect of 13-cis-retinoic acid on wound healing in dogs

13-cis-retinoic acid is currently accepted as a valuable treatment for patients with severe nodulocystic acne. Many of these individuals express interest in surgical scar-correcting procedures. To ascertain the effect of 13-cis-retinoic acid on wound healing, sequential biopsies were examined from partial and full-thickness wounds in dogs following a 2-month course of retinoids. No significant difference was histologically observed from the control animal.     

改良型富血小板纤维蛋白在面部皮肤癌术后软组织缺损修复中的应用

目的探讨A PRF联合腹部全厚皮片移植修复面部恶性非黑色素瘤皮肤癌术后软组织缺损中的可行性及疗效。方法选择于2020年1月至2022年6月徐州医科大学附属淮安医院收治的面部皮肤癌术后需行全厚皮片移植患者80例,并根据随机数字表法将患者分为对照组（行皮片移植,外加多层无菌辅料,n=40）和研究组（将A PRF凝胶覆盖创面后,行皮片移植,外加多层无菌敷料包扎,n=40）,比较两组患者术后创面愈合情况,手术后 1月及 3 个月时患者的瘢痕评估（POSAS）得分,两组患者住院期间的平均换药次数、住院时间以及术后至出院前并发症发生率。结果研究组患者术后7 d的皮片存活率高于对照组（P＜0.05）, 研究组患者术后15 d及21 d的创面愈合情况优于对照组（P＜0.05）,研究组的创面完全愈合时间低于对照组（P＜0.05）;两组患者术后1个月和3个月的POSAS评分比较,差异具有统计学意义（P＜0.05）;研究组的平均换药次数、住院时间以及并发症发生率均低于对照组（P＜0.05）。结论A PRF联合腹部全厚皮片移植能够有效地修复面部恶性非黑色素瘤皮肤癌术后软组织缺损,且减少并发症的发生,减短患者的住院时间,值得临床推广应用。     

Improvement of the breaking strength of wound by combined treatment with recombinant human G-CSF, recombinant human M-CSF, and a TGF-beta1 receptor kinase inhibitor in rat skin

Effective doses of ionizing radiation during preoperative radiotherapy occasionally cause wound complications after subsequent surgery. The authors attempted to accelerate radiation-impaired wound healing in animal models. Recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human macrophage colony-stimulating factor (rhM-CSF), and an inhibitor of transforming growth factor (TGF)-β1 receptor kinase, SB431542, were injected s.c. into a full-thickness incisional wound site in the dorsal skin of rats after local irradiation of X-ray (30 Gy). Wound healing of irradiated skin was assessed using the breaking strength of the wound and histological analyses. The impaired wound healing in irradiated skin was found to be associated with impaired mobilization of bone marrow-derived cells and enhanced expression of TGF-β1 mRNA. The breaking strength of the wound in the irradiated skin was approximately one-eighth of that in the non-irradiated skin; however, following combined treatment with the above three compounds the breaking strength increased to approximately one-half of that in the non-irradiated skin. Histological analysis of the wounded skin revealed an increase in formation of collagen fibers and the panniculus carnosus following the combined treatment. Moreover, the increased breaking strength was associated with an increase in a subpopulation of fibrocytes (collagen I/ED1 double positive cells). These findings suggested that a combined treatment with rhG-CSF, rhM-CSF, and SB431542 is promising as a means of improving radiation-impaired wound healing. ( Cancer Sci 2008; 99: 1021–1028)     

乳腺癌合并高血压患者术后伤口愈合不良分析

目的:分析乳腺癌合并高血压患者行改良根治术后伤口愈合不良的原因,探寻促进伤口愈合的方法。方法:随机选取我院2012年8月-2014年8月收治的76例乳腺癌患者的临床资料,按是否并发高血压分为两组,对照组无并发症37例;并发高血压组39例,对比两组患者伤口愈合情况。结果:对照组平均置管时间（19.1±7.0）天,并发高血压组平均置管时间（29.3±18.3）天,引流量增多。与对照组比较,并发高血压组患者伤口愈合迟缓,两组患者术后伤口愈合情况比较差异有统计学意义（P<0.01）。结论:并发高血压组乳腺癌患者行改良根治术后引流管留置时间较长,伤口愈合较迟缓。积极调控血压,维持血压平稳,术中术后正确医护,将有效促进患者伤口愈合,明显提高患者术后生活质量。     

QUANTITATIVE STUDY ON THE EXPRESSION OF MMP1 AND TIMP1 IN NORMAL AND RADIATION- COMBINED WOUND HEALING AND ITS EFFECTS ON THE HEALING PROCESS

Aim: To study the expression of MMP1 and TIMP1 in normal and radiation- combined wound healing and their effects on the healing process. Materials and Methods: A rat model of radiation - combined wound healing was used, and routine light microscopy, electron microscopy, immunohistochemistry, and in situ hybridization were used to detect the expression of MMP1 and TIMP1 during the healing process. Results:The wound healing process was impaired and delayed. In rats receiving 25Gy Gamma ray locally, the irradiated wounds healed 6 days later than non - irradiated controls. The following changes were found in the expression of MMP1 and TIMP1: ( 1 ) In the early inflammatory phase and in the period of granulation tissue formation, MMP1 expression was only slightly if at all affected in the newly - formed epidermis of irradiated wounds when compared with that in controls. Later, the epidermal expression of MMP1 in irradiated wounds was comparatively increased following the delayed healing process. 3 to 14 days after wounding, TIMP1 was weakly positive in proliferating keratinocytes of control group and became negative after epidermal covering, whereas no or only slight epidermal expression was detected in the irradiated group before epidermal covering. (2) The expression of MMP1 and TIMP1 in irradiated group was markedly decreased in fibroblasts, endotheliocytes and macrophages when compared to that in controls. The expression phase was prolonged due to the delayed healing process. Conclusions: It is concluded that the reduced expression of MMP1 and TIMP1 in granulation tissue retards such impertant processes as cell migration and angiogenesis, thus slowing the healing process. The expression of MMP1 in the newly - formed epidermis may help the process of reepithelialization, but in the late healing period, overexpression of MMP1 and decreased expression of TIMP1 in the epidermis may hinder the establishment of basal membrane and scar formation.     

Exploratory analysis of the bacteriological status of post-irradiation wounds and its relationship to healing

AimsTo investigate the bacteriological status of post-irradiation wounds and its relationship to wound healing in patients with nasopharyngeal cancer.Materials and methodsOne hundred and forty-six nasopharyngeal cancer patients with post-irradiation wounds on one or both sides of the neck were studied prospectively. Swabs were taken from the wounds at the initial study visit for bacteriological examination. A further swab for culture was taken when possible signs of infection developed. Wound healing was assessed on alternate days with respect to wound condition, the presence of clinical infection and healing time.ResultsThe results showed that most of the post-irradiation wounds were colonised with bacteria. This was not associated with clinical signs of infection in any instance. There was no association between wound healing time and the presence of organisms, the identity of organisms, the number of species of organisms, or the use of antibiotics.ConclusionsThe presence of bacteria in post-irradiation wounds, in the absence of clinical signs of wound infection, is not a barrier to wound healing. Oncology practitioners should recognise the unique features of radiation-induced wounds and skin reactions with confidence and provide appropriate treatment as needed.     

开放创面的负压治疗与传统换药治疗疗效对比的Meta分析

目的：应用Meta分析的方法总结评价负压创面治疗（ negative pressure wound therapy,NPWT ）与传统换药对开放创面治疗的疗效。方法检索1993年1月至2013年12月,Cochrane database、Pub med、Embase、中国知网、万方数据库和中国科技期刊数据库,且配合手工检索相关领域的杂志,英文检索关键词：“negative pressure dressing”,“negative pressure therapy”,“negative pressure wound therapy”,“subatmospheric pressure dressing”,“subatmospheric pressure therapy”,“suction dressing”,“topical negative pressure”,“VAC”,“vacuum assisted closure” and “vacuum therapy”,“vacuum sealing”,“foam suction dressing”,“topical negative pressure”and“suction therapy”。中文检索关键词：“VSD”,“VAC”,“负压封闭引流”。纳入应用NPWT与传统换药治疗开放创面的随机对照研究,并应用Rvaman5.1进行Meta分析。结果通过筛选初检文献12214篇,依照纳入及排除标准,最终纳入18个研究（845例）。7个研究以慢性创面愈合时间为观察指标,结果 P＝0.008。P＜0.05,提示 NPWT 组愈合时间短于传统换药组;5个研究以急性创面经治疗后可以关闭创面时间为观察指标,结果P＝0.00001。P＜0.05,提示急性创面经治疗后 NPWT 组可早于传统换药组关闭创面;6个研究以创面大小的改变率为观察指标,结果 P＝0.04。P＜0.05,提示NPWT组创面缩小快于传统换药组。结论 NPWT治疗较传统换药在治疗开放创面存在优势,可缩短急慢性创面闭合时间及加快缩小创面。     

Tissue examination to monitor antiangiogenic therapy: a phase I clinical trial with endostatin.

PURPOSE: The purpose of this study was to determine the effect of the angiogenesis inhibitor endostatin on blood vessels in tumors and wound sites. EXPERIMENTAL DESIGN: In a Phase I dose escalation study, cancer patients were treated with daily infusions of human recombinant endostatin. Tumor biopsies were obtained prior to and 8 weeks after initiation of treatment. Blood vessel formation in nonneoplastic tissue was evaluated by creating a skin wound site on the arm with a punch biopsy device. The wound site was sampled with a second biopsy after a 7-day interval. This sequential biopsy procedure was performed prior to and 3 weeks after initiation of endostatin treatment. Vascular density, endothelial cell kinetics, and blood vessel maturity were determined in tumor and skin wound samples. The ultrastructure of tumor blood vessels was examined by electron microscopy. RESULTS: As expected, the tumors were of variable vascular density. Skin wounding induced a vascular granulation tissue containing a high percentage of proliferating endothelial cells. The proportion of immature blood vessels was high in tumors and in wound sites and low in normal skin. No statistically significant difference was detected between pretreatment and treatment samples of tumors and of skin wounds for any of the parameters tested. CONCLUSIONS: Endostatin treatment was not associated with any recognizable vascular changes in tumor samples and did not perturb wound healing at the doses and the treatment schedule used.     

Daily observations during healing of a full-thickness human surgical wound by second intention

After his preauricular basal cell carcinoma had been excised by Mohs micrographic surgery, a patient took daily photographs of his 6 x 3-cm full-thickness wound as it healed by second intention over the next 44 days. Wound contraction produced a linear decrease in wound area between postoperative days 3 and 40 that accounted for 57% of the area of the original wound. The remainder of the wound was resurfaced by new epithelium, beginning on day 16. Few comparable reports address the contributions of contraction and re-epithelialization in large full-thickness human wounds.     

Wound healing morbidity in STS patients treated with preoperative radiotherapy in relation to in vitro skin fibroblast radiosensitivity, proliferative capacity and TGF-beta activity.

BACKGROUND AND PURPOSE: In a recent study, we demonstrated that the ability of dermal fibroblasts, obtained from soft tissue sarcoma (STS) patients, to undergo initial division in vitro following radiation exposure correlated with the development of wound healing morbidity in the patients following their treatment with preoperative radiotherapy. Transforming growth factor beta (TGF-beta) is thought to play an important role in fibroblast proliferation and radiosensitivity both of which may impact on wound healing. Thus, in this study we examined the interrelationship between TGF-beta activity, radiosensitivity and proliferation of cultured fibroblasts and the wound healing response of STS patients after preoperative radiotherapy to provide a validation cohort for our previous study and to investigate mechanisms. PATIENTS AND METHODS: Skin fibroblasts were established from skin biopsies of 46 STS patients. The treatment group consisted of 28 patients who received preoperative radiotherapy. Eighteen patients constituted a control group who were either irradiated postoperatively or did not receive radiation treatment. Fibroblast cultures were subjected to the colony forming and cytokinesis-blocked binucleation assays (low dose rate: approximately 0.02 Gy/min) and TGF-beta assays (high dose-rate: approximately 1.06 Gy/min) following gamma-irradiation. Fibroblast radiosensitivity and initial proliferative ability were represented by the surviving fraction at 2.4 Gy (SF(2.4)) and binucleation index (BNI), respectively. Active and total TGF-beta levels in fibroblast cultures were determined using a biological assay. Wound healing complication (WHC), defined as the requirement for further surgery or prolonged deep wound packing, was the clinical endpoint examined. RESULTS: Of the 28 patients treated with preoperative radiotherapy, 8 (29%) had wound healing difficulties. Fibroblasts from patients who developed WHC showed a trend to retain a significantly higher initial proliferative ability after irradiation compared with those from individuals in the treatment group with normal wound healing, consistent with the results of our previous study. No link was observed between fibroblast radiosensitivity and WHC. Neither active nor total TGF-beta levels in cultures were significantly affected by irradiation. Fibroblast proliferation in unirradiated and irradiated cultures, as well as radiosensitivity, was not influenced by TGF-beta content. TGF-beta expression in fibroblast cultures did not reflect wound healing morbidity. CONCLUSIONS: These data are consistent with our previous study and combined the results suggest that in vitro fibroblast proliferation after irradiation may be a useful predictor of wound healing morbidity in STS patients treated with preoperative radiotherapy. TGF-beta levels in culture do not predict WHC, suggesting that the role of TGF-beta in wound healing is likely controlled by other in vivo factors.     

LEEP术联合干扰素及重组人白介素-2对宫颈上皮内瘤变伴高危型HPV的疗效

目的 观察并探讨宫颈环形电切术(LEEP)联合干扰素及重组人IL-2对宫颈上皮内瘤变Ⅱ(CIN Ⅱ)伴高危型HPV疗效的影响。方法 选取2012年2月-2013年2月160例行LEEP术的CIN Ⅱ患者并随机分为四组(每组40例):对照组仅采用LEEP术治疗;A组采用LEEP术联合干扰素治疗;B组采用LEEP术联合重组人IL-2治疗;C组采用LEEP术联合干扰素及重组人IL-2治疗。治疗3个月、6个月后复查TCT、阴道镜及HPV,并对患者的疗效、并发症、HPV-DNA转阴率情况进行比较。结果 6个月后C组治愈率及HPV-DNA转阴率分别为92.5%、95%,高于其他三组(P＜0.05);与其他三组相比,C组创面愈合时间、阴道出血时间与阴道排液持续时间更短(P＜0.05)。结论 LEEP联合干扰素及白介素对CIN Ⅱ级伴高危型HPV的治疗效果明显优于单纯采用LEEP术及LEEP术单用干扰素或白介素,且愈合时间短,并发症较少,值得在临床上推广应用。     

The effect of surgical wounding on tumour development.

For more than a century, a role for wound healing in the outgrowth of tumours has been implied based on observations in both experimental and clinical studies. Wound healing can be divided into stages of inflammatory, proliferative, repair and remodelling processes. Through proper regulation of activation of epithelial, endothelial and inflammatory cells, platelets and fibroblasts, and the production of growth factors, wounds heal and the various cell types resume their normal function. In tumour growth, similar processes of cell activation and growth factor production are observed. These processes are, however, differently regulated leading to ongoing cellular activation. In recent years, growth factors such as EGF, TGF-alpha and TGF-beta, bFGF, IGF I and II, and PDGF have been identified to play a role in the different stages of wound healing. In addition, some of these factors have now been identified as also being involved in the outgrowth of tumours. In this review, cell types involved in wound healing and tumour growth, as well as the growth factors and cytokines they produce and the role of the extracellular matrix, extensively present in both conditions, are being discussed. A better understanding of the time interval during which the sequelae of events in wound healing occur in relation to the time interval of tumour recurrence may be the basis for defining new therapeutic strategies that can interfere with tumour outgrowth without affecting wound healing processes. These new therapeutic approaches may be of importance especially after surgery or other invasive (diagnostic) procedures in cancer patients.     

Growth hormone inhibits tumor metastasis

The effect of growth hormone on tumor growth and metabolism in the tumor-bearing host is unknown. This study was done to determine the effect of recombinant growth hormone on primary tumor growth, tumor metastasis, and carcass weight in tumor-bearing animals. Twenty-seven female Lobund/Wistar rats with subcutaneous prostate tumor implants (PA-III) were randomized to receive a standard protein diet (22.0% protein; 4.27 kcal/g) or an isocaloric, protein-depleted diet (0.03% protein; 4.27 kcal/g) ad libitum orally. One half of the animals in each group were randomized to receive daily injections of either recombinant growth hormone (1000 mU/kg/day intramuscularly) or placebo (saline) for 14 days. A significant increase in body weight was observed in growth hormone-treated animals without acceleration of primary tumor growth. Spontaneous pulmonary metastasis was inhibited significantly in animals in both dietary groups treated with growth hormone. Thus, growth hormone selectively supports host growth and inhibits pulmonary metastasis in this tumor-bearing animal model. The potential metabolic effects and clinical consequences of treating cancer patients with growth hormone is discussed.     

Celecoxib can prevent tumor growth and distant metastasis in postoperative setting

Much evidence suggests that an inflammatory condition provides a microenvironment favorable for tumor growth. One of the main components in the healing wound is the induction of cyclooxygenase-2 (COX-2) and prostaglandins, and many solid tumors have been known to overexpress COX-2. The present study investigated the relationship between surgical wounds and tumor growth and the roles of COX-2 and inflammatory reaction in this microenvironment. We created surgical wounds in syngeneic mice for the implantation of SCC VII murine cancer cell line. Accelerated tumor growth and increased angiogenesis by surgical wounds were clearly observed in C3H/HeJ mice with SCC VII tumor. The COX-2 expression of peritumoral tissues and leukocyte infiltration partly explained the accelerated tumor growth, especially in the early phase after surgical wounding. Celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in tumor-implanted mice with surgical wounds. This tumor-suppressive action of celecoxib did not show any noticeable side effects on the late wound healing and on the gastrointestinal tracts. Prophylactic use of the drug can be advocated in many clinical situations, such as residual tumors or contamination of surgical fields by tumor cells.     

Inhibition of tumor implantation at sites of trauma by plasminogen activators

The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B-SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p-nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment.     

Expression of Ricinus communis receptors on epithelial cells in oral carcinomas and oral wounds.

The histological distribution of receptors for Ricinus communis Fraction 1 (RCA1) in oral carcinomas and in oral epithelial cells during wound healing has been studied by use of fluorescein-tagged RCA1. Biopsies from 15 human oral carcinomas and adjacent normal mucosa showed RCA1 receptors at the cell membranes in the basal and spinous layer of the normal epithelium, whereas receptors could not be demonstrated in invading islands of the tumors. In healing oral wounds from eight humans and three monkeys, RCA1 receptors were demonstrated both in normal epithelium adjacent to the wounds and in the epithelial outgrowth from the wound margin. Titrations, however, showed that the epithelial outgrowth reacted more weakly than did the normal adjacent epithelium. These results support previous in vitro studies showing changes in carbohydrate composition of moving normal cells and of malignant cells, a finding that may be of interest in relation to formation of metastases.