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Gastric cancer is the fourth most common cancer worldwide and the leading cause of tumor-related death in China. Gastric cancer is a heterogeneous disease and therefore requires different treatments based on the subtype. We describe a patient who had gastric cancer with liver metastases. Biopsy and tumor analysis using the HercepTest revealed a human epidermal growth factor receptor 2 (HER2)-positive adenocarcinoma as confirmed by fluorescence in situ hybridization. The patient was treated with a regimen of trastuzumab, oxaliplatin, and S-1 (six cycles). When positron emission tomography findings suggested that the metastases had resolved, the patient underwent surgery. Histopathologically, no cancer cells were observed in the resected hepatic tissue. The patient underwent tumor resection surgery, during which the tumor and gastric lymph nodes with lesions were removed. The patient has remained disease-free for 3 months. Therefore, trastuzumab may be an effective agent in the chemotherapeutic treatment of liver metastases in patients with HER2-positive gastric adenocarcinoma.

Background and Purpose: Recently, a number of mimics of the second messenger cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were introduced. In addition, various alterations in the molecule ranging from substitutions at C8 of the base up to full replacement of the ribose moieties still retained biological activity. However, nothing is known about the metabolic stability and cellular effects of these novel analogues., Experimental Approach: cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC. Furthermore, the effect of the analogues on cytokine expression and proliferation was investigated in primary T-lymphocytes and T-lymphoma cells., Key Results: Incubation of cADPR with CD38 resulted in degradation to adenosine diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD-glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5'-diphosphoribose (N1-cIDPR) was not hydrolyzed by CD38. Three additional N1-cIDPR analogues showed a similar stability. Proliferation of Jurkat T-lymphoma cells was inhibited by N1-cIDPR, N1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O-ethoxy)-methyl]-hypoxanthine-cyclic pyrophosphate (N1-cIDP-DE) and N1-ethoxymethyl-cIDPR (N1-cIDPRE). In contrast, in primary T cells neither proliferation nor cytokine expression was affected by these compounds., Conclusions and Implications: The metabolic stability of N1-cIDPR and its analogues provides an advantage for the development of novel pharmaceutical compounds interfering with cADPR mediated Ca2+ signalling pathways. The differential effects of N1-cIDPR and N1-cIDPRE on proliferation and cytokine expression in primary T cells versus T-lymphoma cells may constitute a starting point for novel anti-tumor drugs.

Microcolin A (Mic-1), a marine-derived compound, has been shown to be a novel antiproliferative and immunosuppressive agent. We investigated the ability of Mic-1 and its chemosynthetic analog, microcolin A3 (Mic-3), to induce apoptosis in murine thymocytes. Following incubation of the cells with Mic-1 (10-100 nM) or Mic-3 (10-100 nM), internucleosomal DNA fragmentation in apoptotic cells was detected by agarose gel electrophoresis and the diphenylamine (DPA) assay; the presence of hypodiploid nuclei assessed by propidium iodide (PI) staining; and the percentages of apoptotic and necrotic cells quantified by morphological observation and fluorescein labeled annexin-V binding. Our results show that both Mic-1 and Mic-3 are potent inducers of apoptosis in thymocytes depending on drug concentration and time of exposure, with Mic-3 being more potent than Mic-1 in the induction of apoptosis. Furthermore, flow cytometric analysis using monoclonal antibodies specific to thymocyte subpopulations showed that the proportion of the early immature CD4+ CD8+ T-cell subpopulation in thymocytes was selectively decreased by both agents with a corresponding increase of other subpopulations, indicating that CD4+ CD8+ T cells are the most likely targets of Mic-1 and Mic-3. These in vitro results suggest that the antiproliferative and immunosuppressive properties of both compounds are possibly associated with apoptosis-inducing events and imply that they may have additional potential value as antineoplastic agents.

A series of 4'-(R)-hydroxy-5'-(S)-hydroxymethyl-tetrahydrofuranyl purines and pyrimidines were synthesized by the reaction of 3,4-epoxy-5-(S,trans)-dimethoxymethyl-tetrahydrofuran and nucleobases under the catalysis of potassium tert-butoxide and 18-crown-6. Compounds 6a, 6c and 7b have shown significant inhibition on the growth of HL-60 cells. The phosphotriester and phosphodiester of isonucleoside 8a-d were synthesized and cytotoxic activities were reported. The conformation of isonucleosides in solution was studied by 1H NMR.

(Sp)-octyl 8-chloroadenosine 3',5'-cyclophosphate(OCC), a newly synthesized cAMP analog, strongly induced growth inhibition and differentiation in human leukemia HL-60 cells. The effects were dose- and time-dependent and irreversible. In flow cytometry, OCC brought about a block at the G1 phase of HL-60 cell cycle. Determined by incorporation assay, OCC was shown to strongly inhibit DNA synthesis without affecting the synthesis of RNA and protein in HL-60 cells. OCC activated the protein kinase A(PKA) in the cytosol of HL-60 cells and inhibited its binding to cAMP. The activities of PKA in the cytosol of HL-60 cells treated with OCC were more significantly increased than those in control cells. It can be concluded that OCC binds itself to PKA in competition with cAMP and, as a result, activates PKA.

The derivatives of 5'-dehydroxymethyl carbocyclic nucleoside were synthesized by condensation of cyclopentenyl chloride and corresponding pyrimidines followed by epoxidation and substitution. All compounds were screened for anticancer and antiviral activities and no activity was found.

A facile synthesis of adenosine 3', 5'-cyclic methylphosphonate (1) and 3', 5'-cyclic methylphosphonothioate (2) was accomplished by treatment of 2'-protected adenosine with O,O-bis (1-benzotriazolyl) methylphosphonate or O,O-bis (1-benzotriazolyl) methylphosphonothioate under mild conditions, respectively. The ability of the compounds to inhibit DNA synthesis in mice hepatoma was tested. A pair of diasteromers of 2'-protected (1) was separated and the configuration at the phosphorus atom was identified.