Humans ; Brentuximab Vedotin ; Ki-1 Antigen ; Antineoplastic Agents ; Immunoconjugates/therapeutic use* ; Lymphoma/drug therapy*

OBJECTIVE: To compare a new thermosensitive recombinant human amelogenin (rhAm) carrier and traditional propylene glycol alginate (PGA) carrier for their characteristics, antibacterial activity, and biocompatibility with human periodontal membrane fibroblasts. METHODS: PGA-rhAm was prepared by mixing 3.3% PGA and rhAm, and CS-βGP-rhAm was prepared by mixing 2% chitosan (CS) with rhAm and then with 60% β-sodium glycerophosphate solution (βGP) as the crosslinking agent. The biophysical properties of the prepared carriers were characterized, and their antibacterial activity was assessed by observing Staphylococcus aureus growth. The biocompatibility of the carriers was evaluated in human periodontal membrane fibroblasts (hPDLFs) using CCK8 assay and scratch test, and mRNA and protein expressions of osteogenic genes of the cells incubated with the carriers were detected using RT-qPCR and Western blotting; osteogenic differentiation of the cells was detected using alkaline phosphatase staining. RESULTS: PGA-rhAm had a viscosity value of 3.262±0.055 Pa.s. CS-βGP-rhAm had a solidification capacity of 6 min at 37 ℃ with a pH value close to that of the oral cavity and a swelling rate of about 90%. CS-β GP-rhAm maintained sustained release of rhAm for over 2 weeks with a self-degradation time over 3 weeks. CS-βGPrhAm more effectively inhibited the growth of S. aureus than rhAm-loaded PGA. While PGA did not obviously affect the proliferation of hPDLFs, both CS-βGP and CS-βGP-rhAm significantly promoted the cell proliferation(P < 0.001). Scratch test showed that after rhAm loading, both CS-βGP and PGA promoted cell migration (P < 0.01). CS-βGP-rhAm significantly enhanced the mRNA expressions of RUNX2 and OCN mRNA level and the protein expressions of Ki67, RUNX2, collagen I, and β-catenin (P < 0.05); PGA-rhAm only enhanced RUNX2 (P < 0.05) and OCN (P < 0.01) mRNA expressions without significant effects on the protein expressions. Alkaline phosphatase staining results showed that CS-βGP, but not PGA, promoted osteogenic differentiation of hPDLFs. CONCLUSION CS-βGP carrier is capable of sustained release of rhAm, inhibiting the growth of S. aureus, and improving the biological activity of hPDLFs without affecting the bioactivity of rhAm after drug loading.
Alginates ; Alkaline Phosphatase ; Amelogenin ; Anti-Bacterial Agents/pharmacology* ; Cell Differentiation ; Cells, Cultured ; Chitosan/pharmacology* ; Collagen ; Core Binding Factor Alpha 1 Subunit ; Delayed-Action Preparations ; Glycerophosphates ; Humans ; Ki-67 Antigen ; Osteogenesis ; Periodontal Ligament ; RNA, Messenger ; Staphylococcus aureus ; beta Catenin

Primary cutaneous anaplastic large cell lymphoma is a rare non-Hodgkin's lymphoma.The tumor cells have the characteristics of anaplastic cells,expressing CD30 but not anaplastic lymphoma kinase.In this study,we reported a case of primary cutaneous anaplastic large cell lymphoma in a Tibetan child and summarized the clinicopathological features,aiming to strengthen the understanding of this disease.
Child ; Humans ; Ki-1 Antigen ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; Skin Neoplasms/pathology*

CD30 is a transmembrane glycoprotein of tumor necrosis factor receptor family, which is expressed differently in various lymphomas. It has specific effects on the proliferation and function of tumor cells. However, the significance of CD30 expression has not been fully recognized by clinicians and pathologists, and the detection and evaluation of CD30 have not been standardized. The role of CD30 in the diagnosis of lymphoma, detection methods and reporting standards are summarized in the paper to improve the understanding of CD30.
Humans ; Ki-1 Antigen ; Lymphoma/pathology*

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare subtype of primary cutaneous lymphoma with a favorable prognosis. Primary cutaneous CD30+ lymphoproliferative disorders, which include C-ALCL and lymphomatoid papulosis, are the second most common group of cutaneous T-cell lymphomas. C-ALCL is comprised of large cells with anaplastic, pleomorphic, or immunoblastic cytomorphology, and indeed, more than 75% of the tumor cells express the CD30 antigen. C-ALCL clinically presents with solitary or localized reddish-brown nodules or tumors, and sometimes indurated papules, and they may be with ulceration covering with dark eschar. Multifocal lesions are seen in 20% of the patients. Extracutaneous dissemination, which mainly involves the regional lymph nodes, occurs in 10% of patients. A 69-year-old man noticed a mild elevated cutaneous lesion containing central ulceration covering with brownish black necrotic tissue on the right lower lip, and the lesion was surgically removed. After the first operation, another skin lesion was developed and the histological examination confirmed the diagnosis, C-ALCL. Eight specimens were excised during the 7-month follow-up period. The patient started the treatment with low-dose oral methotrexate (15 mg/wk) and there was no recurrence for 11 months.
Aged ; Antigens, CD30 ; Diagnosis ; Follow-Up Studies ; Humans ; Lip ; Lymph Nodes ; Lymphoma ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; Lymphoma, T-Cell, Cutaneous ; Lymphomatoid Papulosis ; Lymphoproliferative Disorders ; Methotrexate ; Prognosis ; Recurrence ; Skin ; Ulcer

OBJECTIVETo investigate the effect of ceftriaxone on the intestinal epithelium and microbiota in mice in the early-life stage, as well as the recovery of the intestinal epithelium and reconstruction of intestinal microbiota in adult mice.

METHODSA total of 36 BALB/C neonatal mice were randomly divided into control group and experimental group, with 18 mice in each group. The mice in the experimental group were given ceftriaxone 100 mg/kg every day by gavage within 21 days after birth. Those in the control group were given an equal volume of normal saline by gavage. Immunohistochemistry was used to measure the expression of Ki67, Muc2, and ZO-1 in the intestinal epithelium. qPCR and next-generation sequencing were used to analyze the overall concentration and composition of fecal bacteria.

RESULTSAfter 21 days of ceftriaxone intervention, the experimental group had a significant reduction in body weight, a significant reduction in the expression of Ki67 and ZO-1 and a significant increase in the expression of Muc2 in intestinal epithelial cells, a significant reduction in the overall concentration of fecal bacteria, and a significant increase in the diversity of fecal bacteria compared with the control group (P<0.05). Firmicutes was the most common type of fecal bacteria in the experimental group, and there were large amounts of Staphylococcus and Enterococcus. The experimental group had a certain degree of recovery of the intestinal epithelium, but there were still significant differences in body weight and the structure of intestinal microbiota between the two groups at 56 days after birth (P<0.05).

CONCLUSIONSEarly ceftriaxone intervention significantly affects the development of the intestinal epithelium and the construction of intestinal microbiota in the early-life stage. The injury of the intestinal microbiota in the early-life stage may continue to the adult stage and affect growth and development and physiological metabolism.

Animals ; Animals, Newborn ; Anti-Bacterial Agents ; pharmacology ; Ceftriaxone ; pharmacology ; Female ; Gastrointestinal Microbiome ; drug effects ; Intestinal Mucosa ; drug effects ; Ki-67 Antigen ; analysis ; Mice ; Mice, Inbred BALB C ; Mucin-2 ; analysis ; Zonula Occludens-1 Protein ; analysis

Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV.
Antigens, CD30 ; Financing, Organized ; Hodgkin Disease ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic ; United States Food and Drug Administration

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare primary cutaneous lymphoma that is predominantly composed of large lymphoid cells that express the CD30 antigen. The skin lesion of PCALCL is usually single, ulcerative, and located on the trunk or extremities and rarely the palm. A 25-year-old woman presented with a plaque on the left palm for 20 days. The plaque was walnut-sized and purple to gray colored with erosion in the center. Histopathologic examination showed infiltration of large atypical cells in the dermis. The large tumor cells showed positivity for CD3, CD4, and CD30 and negativity for CD8, CD20, epithelial membrane antigen, and anaplastic lymphoma kinase. PET-CT showed no other hypermetabolic lesion except that on the left palm, and we finally arrived at a diagnosis of PCALCL. The patient was treated with an intralesional injection of methotrexate (25 mg/mL, 0.45 cc). After 3 months of treatment, the walnut-sized plaque had disappeared and a peripheral hyperpigmented patch remained.
Adult ; Antigens, CD30 ; Dermis ; Diagnosis ; Extremities ; Female ; Humans ; Injections, Intralesional ; Lymphocytes ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic ; Lymphoma, Primary Cutaneous Anaplastic Large Cell* ; Methotrexate ; Mucin-1 ; Phosphotransferases ; Skin ; Ulcer

To investigate the effect of silencing DJ-1 on xenografted human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells in nude mice.Xenograft model of human LSCC was established by subcutaneous transplantation of Hep-2 cells in 24 nude mice. The LSCC-bearing nude mice were randomly divided into 3 groups (=8 in each):DJ-1 siRNA low dose group and DJ-1 siRNA high dose group were injected in tumors with 20 μg of DJ-1 siRNA or 40 μg of DJ-1 siRNA in 50 μL, respectively; control group was injected with 5% glucose solution in 50 μL, twice a week for 3 weeks. The weight and size of tumors were measured before injection. The animals were sacrificed 48 h after the final treatment, and the tumors were harvested and weighed. The apoptosis and proliferation of tumor cells were determined; the expressions of Caspase-3 and Ki-67 in tumor specimens were detected with immunohistochemistry. The expression of DJ-1, PTEN, survivin mRNA and protein in tumor tissues were detected by RT-PCR and Western blotting, respectively.Tumor weight in low dose group[(0.66±0.15)g] and high dose group[(0.48±0.11)g] were significantly lower than that in control group[(0.83±0.16)g, all<0.05]. The inhibition rates of low dose group and high dose group were (20.48±0.18)% and (42.16±0.13)%, respectively. Immunohistochemistry showed that the expression of Caspase-3 was increased and Ki-67 was reduced in tumor specimens, compared with the control group (all<0.05). RT-PCR and Western blot results showed that in low dose group and high dose group the mRNA and protein expression of DJ-1 and survivin significantly decreased (all<0.05), while PTEN mRNA and protein content increased (all<0.05).High dose DJ-1 siRNA can inhibit the tumor growth in human LSCC xenograft nude mouse model, which indicates that down-regulating DJ-1 and survivin, and up-regulating PTEN expression may lead to blockage of PI3K-PKB/Akt signaling pathway and promoting tumor cell apoptosis.
Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Carcinoma, Squamous Cell ; chemistry ; genetics ; physiopathology ; Caspase 3 ; analysis ; drug effects ; Cell Line, Tumor ; chemistry ; drug effects ; physiology ; transplantation ; Cell Proliferation ; drug effects ; Down-Regulation ; Gene Expression Regulation ; drug effects ; genetics ; physiology ; Head and Neck Neoplasms ; chemistry ; genetics ; physiopathology ; Heterografts ; drug effects ; physiology ; Humans ; Inhibitor of Apoptosis Proteins ; analysis ; drug effects ; Ki-67 Antigen ; analysis ; drug effects ; Laryngeal Neoplasms ; chemistry ; genetics ; physiopathology ; Mice, Nude ; PTEN Phosphohydrolase ; analysis ; drug effects ; Phosphatidylinositol 3-Kinases ; drug effects ; Protein Deglycase DJ-1 ; pharmacology ; Proto-Oncogene Proteins c-akt ; drug effects ; RNA Interference ; physiology ; RNA, Messenger ; pharmacology ; RNA, Small Interfering ; physiology ; Signal Transduction ; drug effects ; genetics ; physiology

Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.
Adult ; Animals ; Antibiotics, Antineoplastic ; pharmacology ; therapeutic use ; Carcinoma ; drug therapy ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Framycetin ; pharmacology ; therapeutic use ; Humans ; Ki-67 Antigen ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Pancreatic Neoplasms ; drug therapy ; Platelet Endothelial Cell Adhesion Molecule-1 ; genetics ; metabolism ; Ribonuclease, Pancreatic ; genetics ; metabolism