Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study.

Background: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown.

Enhancement of electron-phonon coupling in Cs-overlayered intercalated bilayer graphene.

We have performed high-resolution angle-resolved photoemission spectroscopy (ARPES) on cesium (Cs) intercalated bilayer graphene with a Cs overlayer (Cs-C8CsC8). Low-energy electron diffraction shows a (2  ×  2) pattern consistent with intercalation of a Cs layer similar to bulk C8Cs, in addition to the signature of a nearly commensurate superstructure created by the Cs overlayer. ARPES results reveal folding of the π bands due to the periodic (2  ×  2) potential of the intercalated Cs atoms, together with a free-electron-like state at the [Formula: see text] point.

Integrin alpha4beta1 promotes monocyte trafficking and angiogenesis in tumors.

Monocytes and macrophages extensively colonize solid tumors, where they are thought to promote tumor angiogenesis. Here, we show that integrin alpha4beta1 (VLA4) promotes the invasion of tumors by myeloid cells and subsequent neovascularization. Antagonists of integrin alpha4beta1, but not of other integrins, blocked the adhesion of monocytes to endothelium in vitro and in vivo as well as their extravasation into tumor tissue.

Altered metastatic behavior of human breast cancer cells after experimental manipulation of matrix metalloproteinase 8 gene expression.

Previous work in our laboratory led to the cloning, from the same parent tumor cell line (MDA-MB-435), of two human breast cancer cell lines (M-4A4 and NM-2C5) with opposite metastatic phenotypes. Additional investigations revealed that the nonmetastatic cell line NM-2C5 overexpressed the neutrophil collagenase, matrix metalloproteinase (MMP)-8, relative to its partner. Because other studies have implicated the MMP family in promoting tumor metastasis, we investigated the apparently paradoxical expression of MMP-8 in these cell lines.

Telomerase reverse transcriptase promoter regulation during myogenic differentiation of human RD rhabdomyosarcoma cells.

During terminal differentiation of human and murine cells, telomerase activity and parallel transcription of telomerase reverse transcriptase (hTERT) are inhibited. In this study, we used in vitro and in vivo analyses to determine the role of hTERT promoter elements and associated factors during differentiation-induced inhibition of telomerase expression in RD, a human rhabdomyosarcoma cell line. Assay of telomerase enzyme activity, hTERT mRNA, and reporter gene assays confirmed that the hTERT promoter was silenced during 12-O-tetradecanoylphorbol-13-acetate-induced myogenic differentiation of telomerase-positive RD cells.

Mammary tumor latency is increased in mice lacking the inducible nitric oxide synthase.

Nitric oxide (NO) and its metabolites are implicated in carcinogenesis and metastasis. Both stimulatory and inhibitory effects of NO have been reported in relation to breast cancer and its role in the development of malignancies and metastasis remains uncertain. We have used the polyomavirus middle T antigen (PyV-mT) targeted to the mouse mammary gland and bred into an inducible NO synthase (iNOS)-deficient C57Bl/6 strain to examine a role for nitric oxide in modulating tumors that develop in the complex environment of the whole animal.

A biomechanical study of two postoperative prostheses for transtibial amputees: a custom-molded and a prefabricated adjustable pneumatic prosthesis.

We evaluated an adjustable pneumatic prefabricated prosthesis and a rigid custom-molded prosthesis for immediate postoperative use. Twelve transtibial amputations were performed on cadaver limbs. Differential variable reluctance transducers were placed subcutaneously across the wound edge medially and laterally.

Sustained nitric oxide production in macrophages requires the arginine transporter CAT2.

The aberrant production of nitric oxide (NO) contributes to the pathogenesis of diseases as diverse as cancer and arthritis. Sustained NO production via the inducible enzyme, nitric-oxide synthase 2 (NOS2), requires extracellular arginine uptake. Three closely related cationic amino acid transporter genes (Cat1-3) encode the transporters that mediate most arginine uptake in mammalian cells.

Normal reproductive and macrophage function in Pem homeobox gene-deficient mice.

Interaction between germ cells and the supporting somatic cells guides many of the differentiative processes of gametogenesis. The expression pattern of the Pem homeobox gene suggests that it may mediate specific inductive events in murine reproductive tissues. During gestation, Pem is expressed in migrating and early postmigratory primordial germ cells, as well as in all embryo-derived extraembryonic membranes.

Effect of a new rifamycin derivative, rifalazil, on liver microsomal enzyme induction in rat and dog.

1. The effect of a new rifamycin derivative, rifalazil (KRM-1648), on liver microsomal enzyme induction was studied in rat and dog with repeated oral administration of the compound. Relative liver weight, cytochrome b5 and P450 contents, enzyme activities of NADPH-cytochrome c reductase, aniline hydroxylase, p-nitroanisole O-demethylase, aminopyrine N-demethylase, and erythromycin N-demethylase were measured.

Recurrent toxin-mediated perineal erythema.

Background: Important new diseases due to bacterial toxins functioning as superantigens have been described with increasing frequency within recent years. Toxic shock syndrome, recalcitrant erythematous desquamating disorder, streptococcal toxic shock-like syndrome, and, most recently, mucocutaneous lymph node syndrome (Kawasaki disease) have been etiologically linked with certain staphylococcal and streptococcal toxins. We describe two patients with a novel clinical presentation of toxin-mediated disease, which shares certain clinical features with mucocutaneous lymph node syndrome.

A mammalian arginine/lysine transporter uses multiple promoters.

The mCAT-2 gene encodes a Na(+)-independent cationic amino acid (AA) transporter that is inducibly expressed in a tissue-specific manner in various physiological conditions. When mCAT-2 protein is expressed in Xenopus oocytes, the elicited AA transport properties are similar to the biochemically defined transport system y+. The mCAT-2 protein sequence is closely related to another cationic AA transporter (mCAT-1); these related proteins elicit virtually identical cationic AA transport in Xenopus oocytes.

Toxicity of the protein kinase C inhibitor safingol administered alone and in combination with chemotherapeutic agents.

Safingol [(2S,3S)-2-amino-1,3-octadecanediol] potentiates the toxicity of doxorubicin (DOX) and cisplatin (CIS) against tumor cells in vitro and in vivo. The present studies were conducted in rats and dogs to evaluate safingol toxicity when administered i.v.

The Pem homeobox gene is X-linked and exclusively expressed in extraembryonic tissues during early murine development.

We previously reported the isolation of a cDNA clone for a homeobox-containing gene designated Pem, shown by Northern analysis of Day 7 through Day 16 mouse embryos to be expressed in extraembryonic tissues. In this study, Pem gene expression was further examined using in situ hybridization and immunocytochemistry to determine the spatial distribution of Pem transcripts and protein in peri-implantation embryos and in embryoid bodies (EBs). Low amounts of Pem mRNA were detected in undifferentiated EBs.

Inhibition of testicular steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats: evidence that the key lesion occurs prior to or during pregnenolone formation.

The mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment decreases testosterone (T) secretion without significantly altering plasma luteinizing hormone (LH) concentrations was investigated. Testes from sexually mature Sprague-Dawley rats dosed 7 days earlier with 100 micrograms TCDD/kg secreted 30-75% less T than did testes from control rats when perfused in vitro with the LH analog human chorionic gonadotropin (hCG). This decrease confirms that testicular responsiveness to LH, the hormone which regulates T secretion in vivo, is impaired by TCDD treatment.

A novel oncofetal gene is expressed in a stage-specific manner in murine embryonic development.

A novel cDNA clone obtained from a murine T-lymphoma library hybridizes to transcripts expressed in placenta and embryos (Pem) in a stage-specific manner. The Pem cDNA sequence predicts an intracellular hydrophilic protein with no significant sequence similarity to other DNA or protein sequences. Pem transcripts are abundant in 7- and 8-day mouse embryos, but decrease precipitously thereafter.

Species differences in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and biotransformation in fish.

Rainbow trout, yellow perch, carp, bluegill, largemouth bass, and bullhead were treated with graded doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 1, 5, 25, or 125 micrograms/kg) or vehicle, ip. The lethal potency of TCDD tended to be greater in yellow perch, carp, and bullhead than in the other three species (LD50 80 days post-treatment, 3-5 versus 10-16 micrograms/kg, respectively). All species treated with the highest dose of TCDD (125 micrograms/kg) displayed a latency period of 1-4 weeks prior to death; longer latency periods were produced by lower lethal doses.

2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in yellow perch (Perca flavescens).

Growth, mortality and morphologic lesions in juvenile, hatchery-reared yellow perch, Perca flavescens, were studied after treatment with graded single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1-125 micrograms/kg, intraperitoneally). TCDD doses of 25 and 125 micrograms/kg caused 95% mortality by 28 d after treatment, without decreasing body weight. A TCDD dose of 5 micrograms/kg resulted in progressive loss of body weight with cumulative mortality of 80% by 80 d posttreatment.

Morphologic lesions and acute toxicity in rainbow trout (Salmo gairdneri) treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

To determine effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on growth, mortality, and morphologic lesions in rainbow trout, juvenile Shasta or Wytheville strain fish, obtained from 4 hatcheries, were administered graded single doses of TCDD, 0.1-125 micrograms/kg, ip. TCDD doses of 25 and 125 micrograms/kg caused 85% lethality 2-4 wk after treatment.

Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with immune responses of rainbow trout.

Chlorinated dioxins, as typified by the most potent isomer, TCDD, are immunosuppressive in mammalian species and can enhance the susceptibility to a number of diseases. In recent years chlorinated dioxins have been detected in fish in many freshwater and marine habitats. Thus far, the effects of these chemicals on the immune responses of fish have not been examined.

Effect of membrane cholesterol depletion on the immunoreactivity of the D antigen and IgG anti-D.

The immunoreactivity of the main Rh antigen (D) and its corresponding antibody, as determined by a ti-IgG to IgG combining ratio, antibody dissociation and antigen accessibility to antibody, was examined in cholesterol depleted human red cells and ghost membranes. The anti-IgG reactivity of IgG anti-D bound to cholesterol depleted red cells and ghosts was demonstrably enhanced in vitro and in electron microscopy studies, particularly in ghosts. Dissociation of cell bound anti-D during buffer incubation was greater after cholesterol depletion, especially in ghosts.

2,3,7,8-Tetrachlorodibenzo-p-dioxin metabolism and disposition in yellow perch.

Accumulation, tissue distribution, and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-derived 3H were examined in fingerling yellow perch fed a diet containing 494 ppt of [3H]TCDD for 13 weeks followed by the same diet without TCDD for 13 weeks. None of the TCDD-exposed perch showed any signs of overt toxicity such as reduced growth rate, fin necrosis, cutaneous hemorrhage, or lethality. At the end of the 13-week exposure period, 78% of the total body burden of TCDD-derived 3H was contained in the carcass and visceral fat while the remaining 22% was distributed among the liver (9%), gill (5%), skin (3%), skeletal muscle (2%), gastrointestinal tract (1%), pyloric caeca (1%), kidney (less than 1%), spleen (less than 1%), and heart (less than 1%).

Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rainbow trout.

Accumulation, tissue distribution, and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-derived 3H were studied in fingerling rainbow trout fed a diet containing 494 ppt [3H]TCDD for 13 weeks followed by the same diet without TCDD for 13 weeks. This exposure did not cause fin rot, cutaneous hemorrhage, reduced growth rate, or an increase in relative lethality in TCDD-exposed fish. Visceral fat, carcass, skin, and pyloric caeca and all fatty tissues, accounted for greater than 90% of the TCDD-derived 3H in the fish after the 13-week exposure period.