lewis-y-antigen and Skin-Neoplasms

We report a first-in-man trial of a humanized antibody (hu3S193) against the Le(y) antigen.. Patients with advanced Le(y)-positive cancers received four infusions of hu3S193 at weekly intervals, with four dose levels (5, 10, 20, and 40 mg/m(2)). The first infusion of hu3S193 was trace labeled with Indium-111, and biodistribution, pharmacokinetics, tumor uptake, and immune response were evaluated in all patients.. A total of 15 patients (7 male/8 female; age range, 42-76 years; 6 breast, 8 colorectal cancer, and 1 non-small-cell lung cancer) were entered into the study. Transient grade 1 to 2 nausea and vomiting was observed following infusion of hu3S193 at the 40 mg/m(2) dose level only. There was one episode of dose-limiting toxicity with self-limiting Common Toxicity Criteria grade 3 elevated alkaline phosphatase observed in one patient with extensive liver metastases. The biodistribution of (111)In-hu3S193 showed no evidence of any consistent normal tissue uptake, and (111)In-hu3S193 uptake was observed in cutaneous, lymph node, and hepatic metastases. Hu3S193 displayed a long serum half-life (T(1/2)beta = 189.63 +/- 62.17 h). Clinical responses consisted of 4 patients with stable disease and 11 patients with progressive disease, although one patient experienced a 89% decrease in a lymph node mass, and one patient experienced inflammatory symptoms in cutaneous metastases, suggestive of a biological effect of hu3S193. No immune responses (human anti-human antibody) to hu3S193 were observed.. Hu3S193 is well tolerated and selectively targets tumors, and the long half-life and biological function in vivo of this antibody makes it an attractive potential therapy for patients with Le(y)-expressing cancers.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Female; Humans; Immunotherapy; Indium Radioisotopes; Lewis Blood Group Antigens; Male; Middle Aged; Neoplasms; Skin Neoplasms; Time Factors; Tissue Distribution; Treatment Outcome

Malignant melanoma is a destructive and lethal form of skin cancer with poor prognosis. An effective treatment for melanoma is greatly needed. Ginsenoside Rg3 is a herbal medicine with high antitumor activity. It is reported that abnormal glycosylation is correlated with the tumor cell growth. However, the antitumor effect of Rg3 on melanoma and its mechanism on regulating glycosylation are unknown. We found that Rg3 did not only inhibit A375 melanoma cell proliferation in a dose-dependent manner, but also decreased the expression of fucosyltransferase IV (FUT4) and its synthetic product Lewis Y (LeY), a tumor-associated carbohydrate antigen (TACA). Knocking down FUT4 expression by siRNA dramatically reduced FUT4/LeY level and inhibited cell proliferation through preventing the activation of EGFR/MAPK pathway. Consistently, the inhibitory effect of the Rg3 and FUT4 knockdown on melanoma growth was also seen in a xenograft melanoma mouse model. In conclusion, Rg3 effectively inhibited melanoma cell growth by downregulating FUT4 both in vitro and in vivo. Targeting FUT4/LeY mediated fucosylation by Rg3 inhibited the activation of EGFR/MAPK pathway and prevented melanoma growth. Results from this study suggest Rg3 is a potential novel therapy agent for melanoma treatment.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Down-Regulation; Fucosyltransferases; Ginsenosides; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; MAP Kinase Signaling System; Melanoma; Mice; Mice, Nude; Skin Neoplasms; Xenograft Model Antitumor Assays

Kaposiform hemangioendothelioma (KH) is a rare tumor of childhood often associated with Kasabach-Merritt phenomenon (KMP) and occasionally lymphangiomatosis. Although generally considered distinct from other vascular neoplasms, its rarity has precluded a thorough study of its immunophenotypic profile and long-term behavior. Thirty-three cases of KH were reviewed and immunostained for alpha-smooth muscle actin, various endothelial markers (CD31, CD34, vWf, FLI1), a platelet marker (CD61), and the juvenile hemangioma-associated markers GLUT-1 and Lewis Y antigen (LeY). In addition, the presence of HHV-8 was evaluated by RT-PCR. The patients (20 males and 13 females) ranged in age from 2 weeks to 20 years (mean 3 years 9 months). Tumors developed on the extremities (17 cases), head/neck (8 cases), and other sites (8 cases) and affected both superficial and deep soft tissue. Those in the skin presented as slightly raised blue-red lesions. More than half of the patients presented with KMP (14 of 25). Tumors consisted of irregular, infiltrating nodules of compressed vessels, which modulated between areas resembling a capillary hemangioma and Kaposi sarcoma (KS). Endothelial cells in nodules were CD31, CD34, and FLI1 positive but negative for GLUT1 and LeY. Scattered "epithelioid" or glomeruloid islands featuring endothelium associated with clusters of plump alpha-smooth muscle actin-positive pericytes, stippled hemosiderin, and CD61-positive fibrin thrombi likely represent the morphologic sites of platelet consumption. Small and large lymphatic channels occurred in 22 of 33 cases and were typically seen peripheral or deep to the main tumor mass. HHV-8 transcripts were not identified (0 of 3 cases). Follow-up information was available in 22 patients (range 8 months to 15 years; mean 2 years) and indicated that 3 died of disease, 8 were alive with disease, and 10 were alive without residual disease. Two patients developed regional perinodal soft tissue involvement, but none developed distant metastases. KH is a lesion having both a vascular and lymphatic component. Its common association with KMP probably relates in part to unique architectural features that favor turbulent blood flow and platelet activation. KH can also be reliably separated from JH by GLUT-1 and LeY immunostaining, indicating differences in the morphologic and functional attributes of the endothelium between the two lesions. The absence of HHV-8 in KH underscores a different pathogenesis from K

Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Child, Preschool; Diagnosis, Differential; Female; Glucose Transporter Type 1; Hemangioendothelioma; Humans; Immunoenzyme Techniques; Infant; Infant, Newborn; Lewis Blood Group Antigens; Male; Monosaccharide Transport Proteins; Sarcoma, Kaposi; Skin Neoplasms

Infantile hemangiomas are common tumors, distinctive for their perinatal presentation, rapid growth during the first year of life, and subsequent involution-and for their expression of a unique immunophenotype shared by placental microvessels. Occasional "hemangiomas" differ from the classic form in presenting fully formed at birth, then following a static or rapidly involuting course. These congenitally fully developed lesions have generally been assumed to be clinical variants of more typical, postnatally developing hemangiomas. This assumption has not been tested by rigorous histologic and immunophenotypic comparisons.. To compare the histologic and immunohistochemical features of congenital nonprogressive hemangiomas with those of typical, postnatally proliferating, hemangiomas.. All cellular vascular tumors resected from infants younger than 4 months at Arkansas Children's Hospital, Little Rock, over the past 20 years (43 lesions from 36 patients) were first characterized histologically and immunohistochemically, then clinically by chart review.. A university-affiliated pediatric hospital.. Histologic appearance, immunoreactivity for the infantile hemangioma-associated antigens GLUT1 and LeY, and clinical behavior.. Congenital nonprogressive hemangiomas differed from postnatally proliferating infantile hemangiomas in histologic appearance and immunohistochemical profile. Distinguishing pathologic features of these tumors were lobules of capillaries set within densely fibrotic stroma containing hemosiderin deposits; focal lobular thrombosis and sclerosis; frequent association with multiple thin-walled vessels; absence of "intermingling" of the neovasculature with normal tissue elements; and lack of immunoreactivity for GLUT1 and LeY.. Congenital nonprogressive hemangiomas are histologically and immunophenotypically distinct from classically presenting hemangiomas of infancy, unlikely to be related to the latter in pathogenesis.

Topics: Female; Glucose Transporter Type 1; Hemangioma; Humans; Immunohistochemistry; Infant; Infant, Newborn; Lewis Blood Group Antigens; Male; Medical Records; Monosaccharide Transport Proteins; Retrospective Studies; Skin Neoplasms

We semiquantitatively analyzed expression of PCNA and LeY in seborrheic keratosis (SK), actinic keratosis (AK), Bowen's disease (BD), and squamous cell carcinoma (SCC), using immunocytochemically stained tissue sections. PCNA expression increased in a stepwise fashion from low levels in normal skin to higher expressions within SK, AK, BD, and SCC. The levels of LeY protein also increased in this order. The PCNA expression pattern shifted from expression limited to the basal and suprabasal cell layers (in normal skin and SK) to expression extending to the upper squamous and granular layers (in AK, BD, and SCC). On the other hand, the pattern of LeY expression shifted from the granular (in normal skin) to the upper squamous (in SK and AK) and suprabasal layers (in BD and SCC). These findings suggest that PCNA expression is related to the degree of cell proliferation and that LeY expression is related to the degree of differentiation or keratinization of tumor cells. In addition, PCNA and LeY show a reciprocal relationship in their expression.

Topics: Bowen's Disease; Carcinoma in Situ; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratosis, Seborrheic; Lewis Blood Group Antigens; Proliferating Cell Nuclear Antigen; Skin Neoplasms

To determine whether keratoacanthoma (KA) is unique or a variant of squamous cell carcinoma (SCC), the expressions of proliferating cell nuclear antigen (PCNA) and Le(Y) in 16 KA cases (11 fully developed and 5 involutional types; two of the involutional types transformed from the fully developed types) and 11 cases of well-differentiated SCC were investigated by immunohistochemistry. The monoclonal antibodies used were PC-10 for PCNA and BM-1/JIMRO for Le(Y). Le(Y) is one of the Lewis-type antigens, and is thought to be related to apoptosis. In most of the cases of fully developed KA, the PCNA expression was linear or band-like and was limited to the basal and suprabasal layers, while the Le(Y) expression was seen in a diffuse pattern throughout the epidermis, except for the basal layer. However, in 5 of these cases, there were some areas in the basal and suprabasal layer where PCNA-positive cells were few, while Le(Y) expression was very strong. In the involutional Ka cases, the PCNA expression was very weak in the basal and suprabasal layers, and the Le(Y) expression was strong throughout the epidermis. In the SCC cases, the PCNA and Le(Y) expressions were very strong and diffuse throughout the tumor masses except for the lack of PCNA in the horny layer and the lack of Le(Y) in the basal layer. These findings indicate that there are some differences between KA and SCC in the expression pattern of PCNA and Le(Y), and that apoptosis may occur in the Le(Y)-positive areas in the basal and suprabasal layers and thus cause the involution of KA.

Topics: Aged; Aged, 80 and over; Apoptosis; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratoacanthoma; Lewis Blood Group Antigens; Male; Middle Aged; Proliferating Cell Nuclear Antigen; Skin Neoplasms