Phase 1 Clinical Trial of PPMX-T003, a Novel Human Monoclonal Antibody Specific for Transferrin Receptor 1, to Evaluate Its Safety, Pharmacokinetics, and Pharmacodynamics.

This study aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of PPMX-T003, a novel human monoclonal antibody for transferrin receptor 1 (TFR1), in healthy individuals. Forty participants were enrolled and randomized to PPMX-T003 dose groups (n = 6/group) and the placebo group (n = 10). The safety and pharmacokinetics profiles were assessed according to the sequential, ascending single-dose intravenous infusions of PPMX-T003 from 0.

Potential of Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, as a hot tumor inducer.

The tumor microenvironment is one of the most important factors determining the efficacy of cancer immunotherapy. In particular, variability in efficacy has been linked to whether tumors are hot or cold, with hot tumors exhibiting greater T cell infiltration and responding better to immunotherapy. Z-100 extracted from Mycobacterium tuberculosis Aoyama B strain has been reported to increase cytokine production from immune cells.

Peptidoglycan-Like Components in Z-100, Extracted from Strain Aoyama B, Increase IL-12p40 via NOD2.

Background: Z-100 is a hot-water extract of the human-type strain Aoyama B. While Z-100's macrophage-mediated immunomodulatory effects have been reported, the mechanistic details have not been fully clarified. Here, we studied the immunomodulatory effects of Z-100 on mouse bone marrow-derived cells, human CD14 cells, and skin.

A comparison of HER2/neu accumulations of Ga-67-labeled anti-HER2 antibody with chemically and site-specifically conjugated bifunctional chelators.

Monoclonal antibodies (mAb) developed to target specific cancers have achieved considerable success to date. To further enhance therapeutic efficacy, monoclonal antibodies may be conjugated with a cytotoxic drug or radioisotope. We present the development of a new method based on site-specific conjugation (SSC) for targeting HER2.

Z-505, an Oral Ghrelin Receptor Agonist, Attenuates Anorexia After Total Gastrectomy in Rats.

Background: Anorexia is a serious problem in patients with gastric cancer who have undergone gastrectomy. Ghrelin, an orexigenic hormone primarily secreted from the stomach, has been proposed to prevent anorexia. Significant reduction in plasma ghrelin levels after gastrectomy may contribute to lack of appetite and weight loss.

Z-505 hydrochloride ameliorates chemotherapy-induced anorexia in rodents via activation of the ghrelin receptor, GHSR1a.

Despite its therapeutic advantages, chemotherapy with anti-cancer drugs can cause adverse effects, including anorexia and weight loss. Although most patients with cancer suffer from anorexia during chemotherapy, resulting in the need to suspend or cease treatment and thereby worsening prognosis, treatment options for anorexia remain limited. Ghrelin is an orexigenic hormone that has been proposed to prevent anorexia.

Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.

Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia.

Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, promotes TNF-α production via nucleotide-binding oligomerization domain containing 2 (Nod2)-dependent NF-κB activation in RAW264.7 cells.

Macrophages are a major component of the innate immune system, and the cytokines they secrete are involved in antitumor responses. Z-100 is obtained from hot-water extract of human-type Mycobacterium tuberculosis strain Aoyama B and activates the innate immune response. However, while Z-100 is known to modulate macrophage activity, the mechanism behind this modulation is not fully understood.

Z-100, an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B, prevents spontaneous lymphatic metastasis of B16-BL6 melanoma.

Lymphatic metastasis is common in advanced-stage carcinoma and is associated with a poor prognosis. However, few effective treatments to inhibit it are available. Z-100 is an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B that contains polysaccharides such as arabinomannan and mannan.

Inhibition of P-type ATPases by [(dihydroindenyl)oxy]acetic acid (DIOA), a K+ -Cl- cotransporter inhibitor.

[(Dihydroindenyl)oxy]acetic acid (DIOA) has been used as a potent inhibitor of K+ -Cl- cotransporter (IC(50)=10 microM). Here we found that DIOA inhibited activities of P-type ATPases such as dog kidney Na+,K+-ATPase (IC(50)=53 microM), hog gastric H+,K+-ATPase (IC(50)=97 microM) and rabbit muscle Ca(2+)-ATPase (IC(50)=127 microM). In the membrane preparation of the LLC-PK1 cells stably expressing rabbit gastric H+,K+-ATPase, DIOA inhibited activities of the endogenous Na+,K+-ATPase (IC(50)=95 microM) and the exogenous H+,K+-ATPase (IC(50)=75 microM).

Leukotrienes-mediated effects of water extracts from Sargassum horneri, a marine brown alga, on Cl- absorption in isolated rat colon.

Sargassum horneri is an edible marine brown alga distributed along the seacoast of Japan. Here we examined effects on the water-soluble (ethanol-insoluble) extracts (EIS) from Sargassum horneri on ion transports across the isolated rat colonic mucosa set in Ussing chambers. The nonpolysaccharide fraction of EIS (EIS-2) significantly decreased short-circuit current (Isc) across the mucosa, and increased the tissue conductance (Gt).

Inhibition of small-conductance Cl- channels by the interleukin-1beta-stimulated production of superoxide in rabbit gastric parietal cells.

We have shown previously that the G protein-coupled production of superoxide anion (O2-) leads to closure of small-conductance Cl- channels (0.3-0.4 pS) in the basolateral membrane of rabbit parietal cells.