It has been discovered that disrupting the stromal capsule restores a better vasculature/tumor perfusion and improve T cells infiltration inside the core of a melanoma. The invention relates to the use of drugs or immunoconjugates that target the transmembrane protease ADAM12 and deplete the cells that express it. Since ADAM12 protein is specifically expressed by stromal cells of the tumor stromal capsule and around vessels in models for prostate cancer, neuroendocrine pancreatic cancer and melanoma, an ADAM12 inhibitor is useful in anti-tumor therapies as an adjuvant. The invention encompasses methods, compositions, and kits containing ADAM12 inhibitors for use in the depletion of ADAM12+ stromal cells in cancer patient, particularly together with anti-tumor compounds and treatments.

The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Provided herein are methods of generating sterile male insects. The methods include generating a insect stock comprising females with two X chromosomes each having the same centromere with male insects comprising an X chromosome and a Y chromosome each having the same centromere and mating parental male insects having an X:Y/O genome with normal females, thereby producing the sterile male insects.

Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

Two or more conditional, dominant, lethal gene expression systems provide high levels of penetrance in insects. Lethality is induced at an earlier stage of development and the risk of biochemical resistance is reduced, as compared to a single insect conditional, dominant, lethal gene expression system. The invention is useful for the control of insect populations.

Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

Disclosed are non-human mammals having a modified liver and methods of making such non-human mammals having a modified liver. The modified liver may be characterized by a non-germline, stable integration of a non-endogenous gene targeted to the liver of the non-human mammal. In certain aspects, the modified liver may have greater than at least 30% ablation of the endogenous hepatocyte population of the non-human mammal. In certain aspects, the non-human mammal may comprise at least 30% non-endogenous hepatocytes. The disclosed non-human mammals may be useful for pharmacology, drug absorption, distribution, metabolism, and excretion studies, collectively ADME and toxicology studies (ADME-tox), and/or drug screening.

Disclosed herein transgene construct comprising (i) a first nucleotide sequence, wherein the activity of the protein encoded by said first nucleotide sequence causes death of germ cells in the presence of an exogenous induction agent and (ii) a second nucleotide sequence which targets said construct to avian germ cells, methods of using the same and a transgenic avian provided by such methods.

The present invention provides (1) a method for producing a non-human animal having a humanized liver, comprising transplanting human hepatic stem cells and/or hepatic progenitor cells and/or immature hepatocytes to a liver-damaged non-human animal to induce the differentiation of the cells into hepatocytes, (2) a non-human animal having a humanized liver, produced by the method, (3) a method for examining the pharmacokinetics and/or hepatotoxicity of a test substance, comprising using the animal, (4) a method for producing human hepatocytes, comprising transplanting human hepatic stem cells and/or hepatic progenitor cells and/or immature hepatocytes to a liver-damaged non-human animal to induce the differentiation of the cells into hepatocytes, and (5) a method for examining the pharmacokinetics and/or hepatotoxicity of a test substance, comprising using human hepatocytes produced by the method.

A nucleic acid for the controlled expression of a nucleic acid encoding a pro-apoptotic protein in an individual, including: a regulatory polynucleotide including a minimal promoter and at least one AARE (amino acid response element) nucleic acid, the regulatory polynucleotide being activated in an individual upon consumption of a diet deficient in at least one essential amino acid; and a nucleic acid encoding a pro-apoptotic protein, which is placed under the control of the regulatory polynucleotide.