Risk factors for hemoglobin decline in gastric cancer patients undergoing postoperative chemotherapy: a retrospective analysis.

OBJECTIVE: To investigate the independent risk factors for a decreased hemoglobin level in gastric cancer patients undergoing adjuvant chemotherapy. METHODS: A retrospective study was conducted on 142 gastric cancer patients who received chemotherapy between May 2017 and May 2021 at the Gansu Provincial Cancer Hospital. All patients were subjected to the same regimen of adjuvant chemotherapy combining platinum/taxane and fluorouracil. The correlation between patients' clinicopathological features and the decreased hemoglobin during adjuvant chemotherapy was analyzed. Logistic and LASSO regression analyses were employed to screen for independent risk factors for decreased hemoglobin during adjuvant chemotherapy. RESULTS: Univariate analysis revealed that intraoperative bleeding, pre-chemotherapy anemia, and hypoalbuminemia were risk factors for the decreased hemoglobin in patients during adjuvant chemotherapy (all P < 0.05). Both logistic and LASSO regression analyses corroborated these factors as influential factors in the decrease of hemoglobin (P < 0.05). In addition, both logistic and LASSO regression models demonstrated similar performance in this aspect. The nomogram model was subjected to internal validation, resulting in a C-index of 0.712 (0.629-0.796). The calibration curves exhibited satisfactory alignment with the ideal curve. CONCLUSION: Intraoperative blood loss, pre-chemotherapy anemia, and hypoalbuminemia are independent risk factors for hemoglobin reduction following chemotherapy. Moreover, both the logistic and LASSO regression models exhibited equivalent performance in this context. These findings bear substantial clinical implications, aiding physicians in the management of anemia in patients undergoing chemotherapy.

Induction of apoptotic DNA fragmentation mediated by mitochondrial pathway with caspase-3-dependent BID cleavage in human gastric cancer cells by a new nitroxyl spin-labeled derivative of podophyllotoxin.

PURPOSE: 4-[4''-(2'', 2'', 6'', 6''-tetramethyl-l''-piperidinyloxy) amino]-4'-demethyl-epipodophyllotoxin (GP7) is a new semi-synthesized nitroxyl spin-labeled derivative of podophyllotoxin with anti-leukemic and anti-osteosarcoma effects. The purpose of the present study is to investigate the anti-gastric cancer (GC) effects of GP7 and the possible involvement of caspase pathway in GP7-induced apoptotic DNA fragmentation in human GC cells. MATERIALS AND METHODS: Effects of GP7 on the proliferation of human GC cell lines MKN28, AGS, BGC-823 and HGC-27 in different degrees of differentiation and normal human gastric epithelial cell line GES-1 were studied by MTT assay and compared with the effects of etoposide. Effects of GP7 on cell viability and heat shock protein 90 expression of BGC-823 and HGC-27 cells were analyzed by trypan blue exclusion test and western blotting, respectively. Effects of GP7 on apoptotic DNA fragmentation and caspase pathway of BGC-823 and HGC-27 cells were detected by agarose gel electrophoresis, colorimetric assay and western blotting. Caspase-3 inhibitor was used to manipulate the activity of caspase-3. RESULTS: GP7 inhibited concentration- and time-dependently the proliferation of human GC cells, and the inhibitory effect of GP7 on the proliferation of BGC-823 or HGC-27 cells was 1.15- or 1.21-fold higher than that of etoposide. GP7 downregulated heat shock protein 90, improved the anti-GC effects of adriamycin, cisplatin, 5-fluorouracil and their combinations, induced apoptotic DNA fragmentation, activations of caspase-9 and -3 but not -8, cytochrome-c release and BID cleavage in BGC-823 and HGC-27 cells. Caspase-3 inhibitor abrogated GP7-induced BID cleavage, decreased cytochrome-c release, caspase-9 and -3 activities and apoptotic DNA fragmentation but increased cell viability in BGC-823 and HGC-27 cells. CONCLUSION: Our findings indicate that GP7 is a promising anti-GC derivative of podophyllotoxin, and GP7-induced apoptosis in human GC cells may be mediated by mitochondrial pathway with caspase-3-dependent BID cleavage.

microRNAs in gastric cancer invasion and metastasis.

microRNAs (miRNAs) are fundamental gene regulators that can control cell proliferation, differentiation, and apoptosis during tumor development. These molecules can function as oncogenes or tumor suppressors in human cancers. In gastric cancer (GC), miRNAs play a dual role of either promoting or inhibiting cancer invasion and metastasis. In addition, some miRNAs are involved in only the invasion or metastasis, while other miRNAs have multiple functions and participate in invasion, migration and metastasis. In this review, we will discuss the role of miRNAs in the invasion and metastasis of GC.

Induction of apoptosis through caspase-independent or caspase-9-dependent pathway in mouse and human osteosarcoma cells by a new nitroxyl spin-labeled derivative of podophyllotoxin.

Previous study has found that a new nitroxyl spin-labeled derivative of podophyllotoxin, 4-[4"-(2",2",6",6"-tetramethyl-1"-piperidinyloxy)amino]-4'-demethyl-epipodophyllotoxin (GP7), can induce apoptosis in human leukemia cells. However, there have been no studies about the effects of GP7 on osteosarcoma (OS) cells. Here, we observed the anti-OS effects of GP7 in mouse and human OS cells with the comparison of etoposide. GP7 and etoposide inhibited the proliferation of a panel of mouse and human OS cells in a concentration- or time-dependent manner, and the inhibitory effect of GP7 on the proliferation of mouse LM8 or human U2OS cells was 1.28- or 1.35-fold higher than that of etoposide. GP7 or etoposide augmented the anti-OS effects of methotrexate, adriamycin, cisplatin, or their combination, and the combined inhibitory effects of GP7 with MTX on the proliferation of LM8 cells was higher than those of etoposide with MTX. GP7 arrested the cell cycle in S phase but etoposide in G(2)/M phase. GP7 or etoposide induced sub-G(1) peak, apoptotic DNA fragmentation, activations of caspase-3, -8, -9, and DNA fragmentation factor, downregulation of Bcl-2 and Bcl-xL, upregulation of Bax and Bak, and cytochrome-c release from mitochondria in both mouse and human OS cells. GP7 or etoposide also induced endonuclease G translocation from mitochondria into cytosol in mouse cells. GP7- or etoposide-induced apoptotic DNA fragmentation of human OS cells was inhibited by the pan caspase inhibitor and caspase-9 inhibitor, not by caspase-8 inhibitor whereas it was not inhibited by the pan caspase inhibitor in mouse OS cells. Our findings indicate that GP7 is effective against mouse and human OS cells in vitro. The apoptotic DNA fragmentation in mouse OS cells may be mediated by caspase-independent pathway with the involvement of endonuclease G whereas in human OS cells by caspase-9-dependent pathway downstream of the cytochrome-c-initiated caspase cascade.