Adenocarcinoma

Example 1

1) Tucaresol

Tucaresol (0-1200 μM) is exposed for 72 hours to a panel of human liquid, hematological, and solid tumors such as multiple myeloma, leukemia, colorectal, non-small cell lung cancer (squamous and adenocarcinoma), hepatocellular, renal, pancreatic and breast cancer cell lines, and human non-tumor such as HUVEC, PBMC, skin fibroblast cells lines. Tucaresol is studied either alone or in combination with standard-of-care agents (1-100 μM). All cell lines are grown in standard serum-containing media with an exposure time of 24-144 hours. Cell viability is measured using, for example, the Cell TiterGlo® Viability Assay. The potency (IC₅₀) and efficacy (% cell kill) are determined from the percent cell growth of the vehicle control.

2) Tucaresol Plus PD-1 Antibody

Tucaresol (0-1200 μM) in the presence of a PD-1 antibody is exposed for 72 hours to a panel of human liquid, hematological, and solid tumor such as multiple myeloma, leukemia, colorectal, non-small cell lung cancer (squamous and adenocarcinoma), hepatocellular, renal, pancreatic and breast cancer cell lines, and human non-tumor such as HUVEC, PBMC, skin fibroblast cells lines, and the viability of the cell lines are measured as described above. The viability of the cell lines in the presence of tucaresol plus PD-1 antibody is compared to the viability of the cell lines in the presence of a CTLA-4 antibody plus the PD-1 antibody or PD-1 antibody alone.

3) CTLA-4 Antibody Plus PD-1 Antibody

CTLA-4 antibody in the presence of a PD-1 antibody is exposed for 72 hours to a panel of human liquid, hematological, and solid tumor such as multiple myeloma, leukemia, colorectal, non-small cell lung cancer (squamous and adenocarcinoma), hepatocellular, renal, pancreatic and breast cancer cell lines, and human non-tumor such as HUVEC, PBMC, skin fibroblast cells lines, and the viability of the cell lines are measured as described above.

4) Tucaresol Plus Plinabulin

Tucaresol (0-1200 μM) in the presence of Plinabulin is exposed for 72 hours to a panel of human liquid, hematological, and solid tumor such as multiple myeloma, leukemia, colorectal, non-small cell lung cancer (squamous and adenocarcinoma), hepatocellular, renal, pancreatic and breast cancer cell lines, and human non-tumor such as HUVEC, PBMC, skin fibroblast cells lines, and the viability of the cell lines are measured as described above.

The viability of the cell lines in the presence of tucaresol, tucaresol plus PD-1 antibody, CTLA-4 antibody plus the PD-1 antibody, and tucaresol plus plinabulin are compared.

Example 6

The AST cytotoxicity was evaluated and compared with that of inorganic As(III) using five different types of human cell lines from major organs/tissues: HEK293, immortalized embryonic kidney cells; THP-1, monocytes derived from an acute monocytic leukemia patient; macrophage, macrophage-like cells differentiated from THP-1; HepG2, immortalized cells isolated from a hepatocellular carcinoma; and Caco-2, immortalized cell line derived from a colorectal adenocarcinoma patient (FIG. 5). The results show that AST has much lower cytotoxicity in human cells than As(III). The LC₅₀ values of AST on all the tested cell lines except Caco2 were greater than 250 μM. Caco-2 was relatively more sensitive to AST with a lower LC₅₀ value (150-200 μM). In contrast, the LC₅₀ values of As(III) on all the tested cell lines except macrophage were lower than 25 μM, while that of macrophage was higher (100 μM), suggesting that AST is >10 times less cytotoxic than As(III). AST at 100 μM completely inhibits PfGS-I activity (FIG. 2C), P. falciparum proliferation in blood (FIG. 3) and transmission to mosquitoes (FIG. 4A), but had little effect on most of the tested human cell lines (FIG. 5). Thus, AST is effective against the malaria parasite with limited effect on human cells.

Example 9

In vivo PET/CT imaging was conducted in NCr nude mice bearing bxpc3 (human pancreatic adenocarcinoma cell line) and 4T1 (a murine breast cancer cell line that overexpresses integrin α_vβ3 and CD13) tumor xenografts.

Mice were injected with bxpc3 cells (1 million cells in 150 μL PBS) into the subcutaneous flank of the right shoulder and 4T1 cells (1 million cells in 150 μL PBS) into the subcutaneous flank of the left shoulder. Either the CNGRC-(⁶⁸Ga)NOTA-RGDyK heterodimer (“CNGRC” disclosed as SEQ ID NO: 1), (⁶⁸Ga)NOTA(CNGRC) (“CNGRC” disclosed as SEQ ID NO: 1), or (⁶⁸Ga)NOTA(RGDyK) were injected into the bloodstream via tail vein injection. Blocking studies were conducted for the heterodimer studies by co-injecting 100 times of cyclo(CNGRC) (“CNGRC” disclosed as SEQ ID NO: 1) and cyclo(RGDyK). Small animal PET/CT was performed at 1 hour post injection of tracers (FIG. 14). The heterodimer CNGRC-(⁶⁸Ga)NOTA-RGDyK (“CNGRC” disclosed as SEQ ID NO: 1) showed improved enhanced in in vivo performance (such as longer blood retention, better tumor/non-tumor ratios).