sincalide and Adenocarcinoma

Tumor necrosis factor receptor-associated factor 3 (TRAF3) has specific regulatory effects on a wide range of diseases, including tumors. However, the effect and mechanism of TRAF3 on lung adenocarcinoma (LUAD) are still unknown. The aim of the present study was to make clear the role and potential mechanism of TRAF3 in LUAD.. TIMER2.0 database and western blot were applied to detect the expression of TRAF3 in lung adenocarcinoma tissue. Kaplan-Meier Plotter database was utilized to explore the effect of TRAF3 on the clinical prognosis of lung adenocarcinoma patients. Specific siRNA was used to inhibit the expression of TRAF3 in LUAD cells (A549 and H1299). CCK-8 and EdU assays were performed for assessing LUAD cells proliferation. Wound healing assay and transwell assay were performed for determining cells migration. CCK-8 assay was used to assess the response of the LUAD cells to paclitaxel. TIMER2.0 bioinformatics and western blot were employed to detect the effects of TRAF3 on pyroptosis in LUAD.. TRAF3 was highly expressed in lung adenocarcinoma tissues and cell lines. Patients with TRAF3 hyperexpression had a good prognosis compared to those with lower expression. TRAF3 inhibition notably induced proliferation and migration of LUAD cells. Inhibition of TRAF3 also weakened the sensitivity of LUAD cells to paclitaxel. Moreover, bioinformatics results showed that TRAF3 was positively correlated with the expression of pyroptosis-related genes in LUAD. Western blot assays showed that TRAF3 inhibition visibly decreased the expression of apoptosis-associated speck-like protein (ASC), cleaved caspase-1 and matured- IL-1β.. Inhibition of TRAF3 promotes the proliferation and migration of LUAD cells, and reduces the sensitivity of LUAD cells to paclitaxel. The effects of TRAF3 on LUAD cells were mediated in part by caspase-1-dependent pyroptosis.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Caspases; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Paclitaxel; Pyroptosis; Sincalide; TNF Receptor-Associated Factor 3

ATP-binding cassette E1 (ABCE1) is mainly related to the regulation of viral infection, cell multiplication, and anti-apoptosis. Previous reports confirmed the central role in the regulation of ABCE1 in liver and breast cancer; however, its potential role in gastric adenocarcinoma remains unclear. In our study, siRNA and plasmid were transfected to construct gastric cancer cell lines with low and overexpression of ABCE1, and Western blot, RT-qPCR, and immunohistochemical staining were used to detect ABCE1 expression levels in gastric cancer tissues and cell lines. The effects of ABCE1 on cell growth, metastasis, invasion, cell cycle, and drug resistance were investigated using CCK-8 test, wound healing assay, and clone formation experiment. Functional experiments indicated that si-ABCE1 decreased the proliferation, metastasis, and invasion of gastric adenocarcinoma. Meanwhile, si-ABCE1 has significantly promoted EMT process and enhanced the sensitivity of paclitaxel and cisplatin. In vivo experiments also confirmed that si-ABCE1 group had significantly smaller tumors, and immunohistochemical staining results showed the tumor growth in si-ABCE1 group was reduced obviously. In summary, we found ABCE1 is considered as a crucial role in the evolution of gastric adenocarcinoma and could be a viable therapeutic target for the disease.

Topics: Adenocarcinoma; Adenosine Triphosphate; ATP-Binding Cassette Transporters; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cisplatin; Gene Expression Regulation, Neoplastic; Humans; Paclitaxel; RNA, Small Interfering; Sincalide; Stomach Neoplasms

To evaluate the inhibitory effect and mechanism of capecitabine metronomic chemotherapy on gastric cancer cells. In vitro, the effects of 5-fluorouracil (Fu) metronomic chemotherapy on proliferation, apoptosis, tube formation ability, and angiogenesis were detected. In vivo, Ki-67, CD34 and VEGF were detected by immunohistochemical staining (IHC). Flow cytometry was used to detect the percentage of circulating endothelial progenitors (CEPs), and VEGF and PDGF were detected by ELISA in the peripheral blood of nude mice. The proliferation of the SGC-7901 and AGS gastric cancer cell lines in the metronomic 5-Fu group was decreased compared with the control group in vitro. The total length of the small tubes and tubular junction numbers were significantly lower in the metronomic group than the control group. The VEGF and PDGF levels in the cell culture supernatants were lower in the metronomic group than the control group. Compared with the control group, the CEP percentage was decreased in the peripheral blood of tumor-bearing nude mice following treatment with metronomic 5-Fu or capecitabine chemotherapy. No significant changes were found in the conventional or control group. In the peripheral blood of tumor-bearing nude mice, the VEGF and PDGF levels were decreased in the metronomic groups. Metronomic 5-Fu inhibited the proliferation of gastric cancer cells in vitro and in vivo, and their antitumor effects were non-inferior to those of conventional dose chemotherapy, with mild side effects. Thus, tumor inhibition may be attributed to anti-angiogenesis.

Topics: Adenocarcinoma; Administration, Metronomic; Angiogenesis Inhibitors; Animals; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Blood Cell Count; Capecitabine; Cell Line, Tumor; Culture Media; Drug Screening Assays, Antitumor; Endothelial Progenitor Cells; Fluorouracil; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Morphogenesis; Platelet-Derived Growth Factor; Sincalide; Stomach Neoplasms; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

Forkhead box C2 (FOXC2) is a member of the winged helix/forkhead box (Fox) family of transcription factors. It has been suggested to regulate tumor vasculature, growth, invasion and metastasis, although it has not been studied in cervical cancer. Here, we analyzed FOXC2 expression in cervical tissues corresponding to different stages of cervical cancer development and examined its correlation with clinicopathological characteristics. In addition, we examined the effects of targeting FOXC2 on the biological behavior of human cervical cancer cells.. The expression of FOXC2 in normal human cervix, CIN I-III and cervical cancer was examined by immunohistochemistry and compared among the three groups and between cervical cancers with different pathological subtypes. Endogenous expression of FOXC2 was transiently knocked down in human Hela and SiHa cervical cells by siRNA, and cell viability and migration were examined by scratch and CCK8 assays, respectively.. In normal cervical tissue the frequency of positive staining was 25% (10/40 cases), with a staining intensity (PI) of 0.297 ± 0.520, in CIN was 65% (26/40 cases), with a PI of 3.00 ± 3.29, and in cancer was 91.8% (68/74 cases), with a PI of 5.568 ± 3.449. The frequency was 100% in adenocarcinoma (5/5 cases) and 91.3% in SCCs (63/69 cases). The FOXC2 positive expression rate was 88.5% in patients with cervical SCC stage I and 100% in stage II, showing significant differences compared with normal cervix and CIN. With age, pathologic differentiation degree and tumor size, FOXC2 expression showed no significant variation. On transient transfection of Hela and SiHa cells, FOXC2-siRNA inhibition rates were 76.2% and 75.7%; CCK8 results showed reduced proliferation and relative migration (in Hela cells from 64.5 ± 3.16 to 49.5 ± 9.24 and in SiHa cells from 60.1 ± 3.05 to 44.3 ± 3.98) (P < 0.05).. FOXC2 gene expression increases with malignancy, especially with blood vessel hyperplasia and invasion degree. Targeted silencing was associated with reduced cell proliferation as well as invasion potential.

Topics: Adenocarcinoma; Antigens, CD34; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neovascularization, Pathologic; RNA Interference; RNA, Small Interfering; Sincalide; Uterine Cervical Neoplasms

Gut hormones that modulate the growth of normal pancreas may also modulate the growth of cancers originating from pancreas. This study visualized and compared the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in tumour-free tissue sections of human pancreas (n = 10) and pancreatic ductal adenocarcinomas (n = 12) with storage phosphor autoradiography using radioligands. CCK-B receptors, present in control pancreata, were not detected in any of the pancreatic cancers. BBS receptors were visualized in control pancreata, but they were absent in 10 of 12 pancreatic cancers. In 5 of 12 pancreatic cancers, receptors for secretin were visualized, while binding for secretin was present in all tumour-free pancreata. Conversely, no specific binding of VIP was detected in control pancreata but was identified in 3 of 12 pancreatic cancer specimens. It is concluded that the expression of gut peptide receptors in pancreatic cancer differs from that in tumour-free pancreas. Receptors for these peptides are present in only a minority of pancreatic cancer specimens.

Topics: Adenocarcinoma; Adult; Aged; Autoradiography; Bombesin; Female; Humans; Iodine Radioisotopes; Kinetics; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Receptors, Bombesin; Receptors, Cholecystokinin; Receptors, G-Protein-Coupled; Receptors, Gastrointestinal Hormone; Receptors, Vasoactive Intestinal Peptide; Secretin; Sensitivity and Specificity; Sincalide; Succinimides

An 82-year-old man had his third episode of melanotic stool. Two previous workups had failed to localize the source of bleeding. A Tc-99m labeled RBC scan visualized the gallbladder early in the study. Administration of sincalide visually decreased the activity, confirming gallbladder activity. Three months later, at his second surgery, hepatic metastases were finally identified as the source of bleeding. In retrospect, the hepatic activity is inhomogeneous with at least two cold defects that could have represented hepatic metastases.

Topics: Adenocarcinoma; Aged; Diverticulum; Erythrocytes; Gallbladder; Gastrointestinal Hemorrhage; Hemobilia; Humans; Jejunal Diseases; Liver Neoplasms; Male; Neoplasms, Unknown Primary; Radionuclide Imaging; Sincalide; Sodium Pertechnetate Tc 99m

Cholecystokinin (CCK) exerts an influential effect on the growth of normal pancreas. It is postulated that carcinoma arising from the pancreas may retain some normal pancreatic properties as far as hormone dependency is concerned. In an effort to examine the effect of CCK on the growth of pancreatic cancer, we evaluated the effect of CCK receptor antagonist on the growth of a transplantable adenocarcinoma of the pancreas. For this study we utilized three groups of hamsters with adenocarcinoma of the pancreas transplanted subcutaneously on the right flank. Group I (n = 15) served as control. Group II (n = 15) received CCK receptor antagonist (L-364,718), 0.1 mg/100 g body wt subcutaneously BID. Group III received CCK receptor antagonist in the same dose but treatment was started after tumors became palpable. All animals were examined daily. Latency for tumor growth, tumor size, and body weight were recorded. Animals were sacrificed after 3 weeks and final tumor volume and weight were measured. CCK receptor antagonist (L-364,718) significantly reduced pancreatic carcinoma growth when given immediately after transplantation and also in animals with established tumor. However, this inhibitory effect of L-364,718 was only partial and effective only for a brief time. This finding suggests CCK may have only a minimal influence on the biologic behavior of exocrine pancreatic cancer.

Topics: Adenocarcinoma; Animals; Benzodiazepinones; Cricetinae; Devazepide; Male; Mesocricetus; Neoplasm Transplantation; Pancreas; Pancreatic Neoplasms; Receptors, Cholecystokinin; Sincalide; Succinimides

We recently reported that human pancreatic cancers differentially respond to the growth inhibitory effects of an estradiol (E2) receptor antagonist, tamoxifen, and a long-acting analogue of somatostatin, Sandostatin. In the present study two human pancreatic cancers, established as xenografts in nude mice, were examined as representative of cancers that respond to either tamoxifen (PGER) or Sandostatin (SKI), for the presence of binding sites for various hormones. Male nude mice were inoculated with either SKI or PGER, by passage of tumor chunks (3 mm2) to the interscapular region. Tumors, obtained from mice after approximately 30 days of in vivo growth, were analyzed for binding to cholecystokinin-octapeptide (CCK), somatostatin and E2, by published procedures, using either crude tumor membranes (CCK), cytosol and nuclear fractions (E2), or cryostat sections of whole tumors (somatostatin). SKI was highly positive for high-affinity (Kd = approximately 1 nM) CCK binding sites at the time of resection with a binding capacity of approximately 1000 fmol/mg protein. With increasing passages, the total number of high-affinity binding sites for CCK, were reduced to non-detectable levels in SKI tumors, while non-saturable binding (Kd = greater than 10 nM) became increasingly evident. Early passages of PGER tumors were similarly positive for high-affinity binding sites for CCK, that steeply declined with increasing passages. Specific binding sites for E2, were observed only in the cytosolic fractions of PGER, with a high binding affinity (Kd = approximately 0.05 nM) and a low binding capacity (15 +/- 3 fmol/mg cytosolic proteins), at all passages examined; E2 binding sites were not detected in cytosolic and nuclear fractions of SKI and in the nuclei of PGER, at all passages. SKI and PGER at different passages were examined for somatostatin binding, and both the early and late passages of PGER were devoid of somatostatin binding sites, while SKI tumors were positive for them. Based on the above results, it appears likely that Sandostatin directly inhibited the growth of SKI tumors, since SKI was positive for somatostatin binding sites; it appears less likely that Sandostatin indirectly mediated its inhibition by attenuating possible stimulatory effects of CCK. Growth inhibitory effects of tamoxifen on PGER were apparently via E2 binding sites, since only the tumors positive for E2 binding sites (PGER) responded to tamoxifen; it remains to be determined if tamoxifen

Topics: Adenocarcinoma; Animals; Autoradiography; Carcinoma, Intraductal, Noninfiltrating; Estradiol; Humans; Iodine Radioisotopes; Kinetics; Mice; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms; Receptors, Cholecystokinin; Receptors, Estradiol; Receptors, Neurotransmitter; Receptors, Somatostatin; Sincalide; Somatostatin; Transplantation, Heterologous; Tumor Cells, Cultured

A new cell line was established from a liver metastasis of a human pancreatic adenocarcinoma. The cell line, MDAPanc-3, which arose from a moderately differentiated adenocarcinoma, produces carbonic anhydrase II mRNA, but no detectable levels of insulin or alpha amylase mRNA. The stem line chromosome number was determined to be 43, with six marker chromosomes. Growth of MDAPanc-3 is stimulated by cholecystokinin (CCK) fragment 26-33. The cell line will be useful in further studies on the mechanism(s) by which CCK stimulates growth of certain human pancreatic adenocarcinomas and normal human pancreatic exocrine tissue.

Topics: Adenocarcinoma; alpha-Amylases; Blotting, Northern; Cell Division; Humans; Insulin; Karyotyping; Keratins; Male; Middle Aged; Molecular Weight; Pancreatic Neoplasms; Protein Biosynthesis; RNA, Neoplasm; Sincalide; Tumor Cells, Cultured

In view of the trophic action of gastrointestinal hormones on the exocrine pancreas, the effects of secretin, octapeptide of cholecystokinin (CCK-8), and desglugastrin on the growth of hamster pancreatic well differentiated adenocarcinoma were investigated in vitro. Desglugastrin exhibited the greatest effect on thymidine incorporation into these cells after a lag period of 96 h. Doses of desglugastrin in the range from 30 to 270 ng/mL caused a significant and dose-dependent increase in thymidine incorporation. Higher doses of this peptide led to a decreased response. Secretin also increased thymidine incorporation, but the response was less than that induced by gastrin. Prolonged incubation with secretin for 96 h increased tritiated thymidine incorporation in a log-dose fashion in the range of 30 to 270 ng/mL. Doses of CCK-8 in the range of 90 to 810 ng/mL significantly increased thymidine incorporation after 48 h of incubation. Following 72 h of incubation, only the dose of 270 ng/mL continued to exhibit a significant stimulation. Our study suggests that the gastrointestinal hormones could directly increase the growth of pancreatic carcinoma cells, act synergistically with endogenous growth factors, or stimulate the local production of these factors. In any event, our results that gastrin, secretin, and CCK can stimulate the growth of pancreatic ductal tumor cells in tissue cultures, support earlier findings on normal and malignant pancreatic parenchyma.

Topics: Adenocarcinoma; Amino Acid Sequence; Animals; Cell Cycle; Cell Line; Cricetinae; DNA Replication; DNA, Neoplasm; Gastrins; Kinetics; Molecular Sequence Data; Pancreatic Neoplasms; Secretin; Sincalide; Thymidine; Tritium

This study deals with the effect of four types of COOH-terminal cholecystokinin (CCK) fragments on the growth of xenotransplantable human gastric cancer (SC-6-JCK, a poorly differentiated adenocarcinoma) whose growth has been promoted by pentagastrin. The growth of the tumor was inhibited using daily s.c. injections of CCK-octapeptide (CCK-8) and glutaryl-CCK-8 at a dose of 500 micrograms/kg body weight. After 30 days of treatment with CCK-8 or glutaryl-CCK-8, a significant decrease was observed in the tumor weight (P less than 0.05) and the tumor size P less than 0.01) in comparison with those of the control. But treatment with CCK-12 and pyroglutamyl-CCK-8 did not produce inhibition of tumor growth. Furthermore the correlation between the effect of CCK-8 on the normal rise in tumor cyclic adenosine 3':5'-monophosphate (cAMP) levels caused by pentagastrin injection and tumor growth was studied. The increase of cAMP by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse was significantly inhibited by pretreatment with CCK-8 at concentrations equimolar to pentagastrin (P less than 0.05), while cAMP in the tumor was slightly elevated by a single i.p. injection of CCK-8 alone. Also in the in vitro study, CCK-8 inhibited the increase of cAMP and the activation of cAMP-dependent protein kinase which was stimulated by pentagastrin. These results suggest that proliferation of gastrin-dependent human gastric cancers may be suppressed by CCK in competition with gastrin.

Topics: Adenocarcinoma; Animals; Cholecystokinin; Cyclic AMP; Humans; Mice; Neoplasm Transplantation; Pentagastrin; Protein Kinases; Sincalide; Stomach Neoplasms