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Howard A Reber

Publications and source records attributed to Howard A Reber.

At least 37 records · Page 2Linked to original sources
PubMed2005

Combination therapy for advanced pancreatic cancer using Herceptin plus chemotherapy.

The HER2/neu oncogene is overexpressed in up to 70% of human pancreatic cancer specimens when compared to normal pancreatic tissue. This cell surface receptor can be targeted specifically by the neutralizing antibody Herceptin. Herceptin has been successfully used in combination with other chemotherapeutic agents in breast cancer, a cancer in which only 30% of patients harbor elevated HER2/neu levels. In the present study, we investigated the therapeutic efficacy of Herceptin in combination with gemcitabine and docetaxel. Gemcitabine is currently the standard chemotherapeutic agent used to treat pancreatic cancer. In contrast, docetaxel, a taxane, is only just being investigated in pancreatic cancer. Tumor cell resistance to taxanes is at least in part mediated by the HER2/NEU oncogene. We have previously characterized HER2/NEU expression in human pancreatic cancer cell lines and studied the anti-tumor activity of Herceptin monotherapy in vitro and in vivo. In the present study, combination therapy resulted in a dramatic improvement of animals bearing human pancreatic cancer xenografts. Furthermore, metastasis and production of ascites was lower when a combination of these three agents was used. We conclude that, as with breast cancer, the anti-tumor activity of Herceptin may be improved by combination with taxanes or gemcitabine.

Agar↗
PubMed2005

The proteasome inhibitor MG132 induces apoptosis in human pancreatic cancer cells.

The ubiquitin-proteasome system plays a critical role in the regulation of programmed cell death. Proteasome inhibitors induce apoptosis in various cancer cells and have antitumor effects in murine tumor models. In the present study, we investigated whether the cell-permeable proteasome inhibitor MG132 (carbobenzoxyl-L-leucyl-L-leucyl-L-leucinal) reduced the growth of a human pancreatic cancer cell line through induction of apoptosis in vitro. The effects of MG132 (0.125-1.000 microM) on the growth of the human pancreatic cancer cell line BxPC-3 were analyzed by cell count and MTT assay. Apoptosis was determined by FACS analysis after annexin V and propidium iodide staining and the enrichment of intracellular nucleosomes. The proteasome inhibitor MG132 decreased cell growth of the human pancreatic cancer cell line BxPC-3 in a dose- and time-dependent manner. This effect was at least in part mediated by the induction of apoptosis. A combination therapy with standard cytotoxic agents and proteasome inhibitors could potentially be a novel therapeutic strategy in treatment of pancreatic cancer.

Apoptosis↗
PubMed2004

Antiangiogenic activity of genistein in pancreatic carcinoma cells is mediated by the inhibition of hypoxia-inducible factor-1 and the down-regulation of VEGF gene expression.

BACKGROUND: Previous reports indicate that Genistein, a naturally occurring isoflavonoid, exhibits strong antiangiogenic activity. The underlying mechanism of inhibition, however, remains unclear. Among the biologic effects of Genistein are the inhibition of tyrosine kinases and the inhibition of hypoxic activation of hypoxia-inducible factor-1 (HIF-1), one of the main regulators of VEGF gene expression. METHODS: Hypoxic cell culture was performed in a modular incubator chamber. Vascular endothelial growth factor (VEGF) protein secretion was measured using the enzyme-linked immunosorbent assay, binding of DNA by HIF-1 was measured using the electrophoretic mobility shift assay, and mRNA quantification was performed using Northern blot analysis. Pancreatic carcinoma was studied in an orthotopic murine model. Angiogenesis in vivo was quantified by staining xenograft tumors for endothelial cell markers. RESULTS: VEGF protein secretion was dose-dependently suppressed with increasing doses of Genistein. Furthermore, treatment of pancreatic carcinoma cells with Genistein led to impaired activation of HIF-1 under hypoxic culture conditions. Northern blot analysis indicated that VEGF mRNA expression decreased upon treatment with Genistein, both under normoxic and hypoxic culture conditions. In vivo, Genistein inhibited tumor growth for xenograft pancreatic carcinoma cells, whereas extensive hypoxia was observed in xenograft tumors and was not influenced by Genistein therapy. Similarly, decreased VEGF mRNA levels were observed in Genistein-treated Capan-1 xenograft tumors. CONCLUSIONS: The current study indicates that the previously reported antiangiogenic activity of Genistein probably is mediated by the inhibition of HIF-1, an important regulator of VEGF gene homeostasis, particularly under low-oxygen conditions. Therefore, this bioactive compound may well be beneficial to patients with pancreatic carcinoma.

Animals↗
PubMed2004

Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model.

BACKGROUND: The role of tumor hypoxia has become a major focus in cancer research since it influences both local and systemic tumor growth. Oxygen measurements taken in human pancreatic cancer have shown extremely low oxygen tension. The aim of this study was to develop an orthotopic model for pancreatic cancer that mimics the specific tumor microenvironment and to evaluate the role of tumor oxygenation in local tumor growth and systemic dissemination in this model. MATERIALS AND METHODS: We used two established human pancreatic cancer cell lines for xenobiotic tumor induction. After subcutaneous tumor formation one small tumor piece was transplanted into the pancreatic parenchyma of mice of the different study groups. Upon orthotopic tumor induction tumor oxygenation was measured with the Eppendorf histograph. Histological evaluation was performed with pimonidazole, an in vivo marker of hypoxia. RESULTS: The tumor take rate was 100% in this model. Metastatic tumor dissemination occurred within the abdominal cavity, and distant metastasis were observed in the lung parenchyma. Oxygen measurements taken in various abdominal organs and xenograft tumor showed a high variation between different organs and xenografted tumors. Tumor oxygenation correlated well with the metastatic score in this model. Furthermore hypoxia was found both in the tumor center and also at the rim of a growing tumor mass. A high number of hypoxic cells were detectable in metastases located in the lung parenchyma. CONCLUSION: This study provides experimental evidence that tumor hypoxia influences metastatic disease progression and supports recent assumptions that tumor hypoxia is actively involved in progression of pancreatic cancer. It further demonstrates that tumor hypoxia is not only found in the center of a tumor mass, but also occurs at the invasion front.

Abdominal Neoplasms↗
PubMed2004

Nerve growth factor stimulates MMP-2 expression and activity and increases invasion by human pancreatic cancer cells.

Pancreatic cancer frequently invades and migrates along neural tissue. Although the exact mechanisms are unknown, perineural invasion negatively impacts prognosis for pancreatic cancer patients. Matrix metalloproteinases (MMPs) are overexpressed in pancreatic cancer and are associated with poor prognosis. We hypothesized that nerve growth factor (NGF) released from neural tissue increases the invasive properties of pancreatic cancer cells. In the present study we investigated the effect of NGF on the expression and activity of MMP-2 in human pancreatic cancer cells. NGF dose dependently increased MMP-2 protein in the culture medium and stimulated MMP-2 gelatinolytic activity. This effect was mediated by specific binding of NGF to its receptor trk A, which was detected on all pancreatic cancer cells, with subsequent activation of the p44/42 MAPK signaling pathway. The NGF-induced increase in MMP-2 expression and activity lead to an enhanced invasion in vitro. These findings support the hypothesis that neurotrophic factors, e.g., NGF, are critically involved in mediating perineural invasion of pancreatic cancer.

Cell Line, Tumor↗
PubMed2004

Pancreatic neoplasms.

PURPOSE OF REVIEW: This review includes a summary of articles that have affected the study and treatment of pancreatic neoplasms over the past year. RECENT FINDINGS: Over the past year, there have been several reports of new animal models of pancreatic cancer that recapitulate the human disease and hold promise for preclinical studies. The hope of proteomic and DNA technologies for detecting pancreatic cancer and new genes involved in the biology of this disease are described. New studies examining neoadjuvant and adjuvant treatment of pancreatic cancer show some promise. The surgical treatment and palliation of pancreatic cancer continues to advance. Experiences of the treatment of intraductal pancreatic mucinous neoplasms shed some light on the management of this entity. Two large series of cystic neoplasms point to the evolving management of these often asymptomatic lesions. SUMMARY: The treatment of pancreatic neoplasm continues to change and improve as more is learned about these diseases. A renewed clinical and scientific focus on this organ will certainly shape the management of pancreatic neoplasm and holds the promise of improved outcomes.

Journal Article↗
PubMed2004

Laparoscopic gastrojejunostomy for gastric outlet obstruction in pancreatic cancer.

Up to 20 per cent of patients with pancreatic cancer develop gastric outlet obstruction. Traditionally, these patients have been managed with an open gastrojejunostomy. Laparoscopic gastrojejunostomy may now be a preferable approach. We conducted a retrospective review of nine patients who underwent laparoscopic gastrojejunostomy in 2001-2004. All nine patients had unresectable pancreatic cancer. There were six men and three women. Median age was 66 years (range 36-87). Two patients had prior laparotomies for attempted resection. Four patients had previously placed duodenal stents that failed. Four others had undergone unsuccessful attempts of duodenal stenting. Median operating time was 116 minutes (range 75-300). There were no intraoperative complications or conversions to open procedure. Median time to postoperative oral intake was 4 days (range 3-6), and median postoperative length of stay was 7 days (range 5-18). Eight of our nine patients were palliated successfully using this technique. There were no complications or deaths related to the operation. All patients were discharged from the hospital. Six patients have since died, with a median postoperative survival of 2.5 months (range 1.5-8). Laparoscopic gastrojejunostomy provides safe and effective palliation of gastric outlet obstruction in patients with unresectable pancreatic cancer. This approach allows for rapid palliation in a group of patients with a very limited survival.

Adenocarcinoma↗
PubMed2003

PGE(2) is generated by specific COX-2 activity and increases VEGF production in COX-2-expressing human pancreatic cancer cells.

In some cancers cyclooxygenase (COX) inhibition appears to be anti-mitogenic and anti-angiogenic, but the actions of COX-derived prostaglandins in pancreatic cancer (PaCa) are unknown. In this study COX-2 was detected in three of six PaCa cell lines while COX-1 was identified in all cell lines. COX-2 expression correlated with basal and arachidonic acid (AA) stimulated PGE(2) production. PGE(2) production was inhibited by the COX-2 inhibitor nimesulide. In COX-2 expressing cells, exogenous AA and PGE(2) increased VEGF synthesis via the EP(2) receptor. Whereas PGE(2) stimulated intracellular cAMP formation in COX-2 positive and negative cells, 8-bromo cAMP stimulated VEGF production only in COX-2 expressing cells. Stimulating COX-2 expressing PaCa cell lines with AA enhanced migration of endothelial cells, an effect which was inhibited by a COX-2 inhibitor and EP(2) receptor antagonist. These data identify a subset of human PaCa cell lines that express functional COX-2 enzyme. PGE(2) generated by specific COX-2 activity increases VEGF secretion in human PaCa cells through an autocrine mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2003

Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer.

As with other solid tumors, the growth and metastasis of pancreatic cancer is critically dependent on tumor angiogenesis. A major stimulus for a tumor's recruitment of additional blood vessels is cellular hypoxia, a condition which is especially pronounced in this neoplasm. Hypoxia induces transcriptional activation of genes that alter cellular metabolism and promote neoangiogenesis. Pancreatic cancer cells have demonstrated activation of such adaptive pathways even in the absence of hypoxia. A highly-angiogenic response in this neoplasm correlates with increased tumor growth, increased metastasis, and decreased survival. Pancreatic cancers expressing high levels of vascular endothelial growth factor, a potent pro-angiogenic cytokine, also have a higher incidence of metastasis and poorer prognosis. Pancreatic cancer cells uniquely express receptors for vascular endothelial growth factor, indicating a role for an autocrine loop in tumor proliferation and invasion. Multiple experimental anti-angiogenic strategies, many of which target vascular endothelial growth factor, reduce pancreatic cancer growth, spread, and angiogenesis. Anti-angiogenic treatments for pancreatic cancer will likely be most effective when used as an integral part of a combination chemotherapeutic regimen.

Animals↗
PubMed2003

Improved survival for adenocarcinoma of the ampulla of Vater: fifty-five consecutive resections.

HYPOTHESIS: After resection of an adenocarcinoma of the ampulla of Vater, certain clinical and pathologic characteristics influence long-term survival. DESIGN: Retrospective case series. SETTING: Major academic medical and pancreatic surgical center. PATIENTS: Fifty-five consecutive patients who underwent Whipple resection for ampullary adenocarcinoma from 1988 through 2001. INTERVENTIONS: Pylorus-preserving Whipple resection in 32 patients and standard Whipple resection in 23 patients. MAIN OUTCOME MEASURES: Postoperative survival. A multivariate Cox proportional hazards model was used to determine the effects of various factors on long-term survival after resection. RESULTS: There were no operative deaths, and all patients left the hospital. After a mean follow-up of 46.9 months, the overall 5-year Kaplan-Meier survival estimate was 67.7%. The median survival of the entire group has not yet been reached. Five-year postoperative survival estimates for node-negative (n = 32) and node-positive patients (n = 23) were 76.5% and 53.4%, respectively (P =.26). Patients whose tumors demonstrated perineural invasion (n = 12) had a 5-year survival estimate of 29.2% vs 78.8% for those whose did not (P<.001). On multivariate analysis, the absence of perineural invasion (P<.001) was an independent predictor of significantly improved postoperative survival. CONCLUSIONS: Compared with previous reports from our own and other centers, this series demonstrates improved postoperative survival by 10% to 20% in patients undergoing Whipple resection for adenocarcinoma of the ampulla of Vater. The reasons for this improved outcome are unclear, and the effect of adjuvant treatment cannot be determined from this analysis. The major factor associated with prolonged survival was the absence of perineural invasion in the resected tumor specimen.

Adenocarcinoma↗
PubMed2003

Pancreatic cancer growth is inhibited by blockade of VEGF-RII.

BACKGROUND: Angiogenesis is important in the development and progression of pancreatic cancer. Therefore antiangiogenic therapy targeting endothelial cells may represent a promising therapeutic option. The aim of the study was to evaluate antiangiogenic therapy as a potential therapeutic option in pancreatic cancer. METHODS: Replication-deficient retroviruses encoding truncated VEGF-RII were used to block vascular endothelial growth factor (VEGF) signaling. Tumor growth of 3 pancreatic cancer cell lines was assayed in a nude mouse model in which each pancreatic cancer cell line was subcutaneously inoculated together with retrovirus-producing cells. Expression of VEGF was assayed by RT-PCR and by enzyme-linked immunosorbent assay. Oxygen tension in tumors was determined polarographically. RESULTS: All 3 pancreatic cancer cell lines expressed VEGF mRNA, with the highest VEGF secretion seen in MIA PaCa-2 cells. In vivo therapeutic intervention through dominant negative inhibition of VEGF-RII significantly reduced the growth rate of subcutaneous tumors and inhibited tumor neoangiogenesis. Tumor oxygenation, however, was not altered in xenograft tumors treated with dominant negative retroviruses. CONCLUSION: The ligand/receptor system consisting of VEGF and VEGF-RII seems to be of biologic significance in the pathogenesis of pancreatic cancer growth. Therefore therapeutic intervention in this angiogenic system by a retroviral-based gene transfer technology represents a rational and feasible new technique to inhibit tumor growth.

Animals↗
PubMed2003

Evaluation of vascular endothelial growth factor blockade and matrix metalloproteinase inhibition as a combination therapy for experimental human pancreatic cancer.

Blockade of vascular endothelial growth factor (VEGF) and inhibition of matrix metalloproteinases (MMP) are promising therapies for cancer. This study assessed the effects of a neutralizing anti-VEGF antibody (A4.6.1) and an MMP inhibitor (BB-94) on pancreatic cancer (PaCa) in vivo. Five million cells of two human PaCa cell lines (AsPC-1 and HPAF-2) were injected subcutaneously into nude mice; 1 mm(3) fragments of the resulting tumors were implanted into the pancreas of other mice. Animals were randomized into a control group and three treatment groups: A4.6.1 (100 microg intraperitoneally twice weekly); BB-94 (50 mg/kg every other day); and combination (A4.6.1 plus BB-94). Treatment was started after 3 days and continued for 14 weeks. Tumor volume, local and distant spread (score), and ascites were determined at autopsy. Microvessel density as a parameter of neoangiogenesis was analyzed in CD31-stained tumor sections. Both monotherapies reduced tumor volume (HPAF-2: -89% by A4.6.1 and -75% by BB-94; AsPC-1: -48% by A4.6.1 and -72% by BB-94), spread (HPAF-2: -76% by A4.6.1 and -58% by BB-94; AsPC-1: -32% by A4.6.1 and -54% by BB-94), and microvessel density (HPAF-2: -75% by A4.6.1 and -30% by BB-94; AsPC-1: -59% by A4.6.1 and -30% by BB-94), resulting in a tendency toward increased survival (HPAF-2: 8 of 8 animals by A4.6.1 or BB-94 vs. 4 of 8; AsPC-1: 3 of 8 by A4.6.1, 4 of 8 by BB-94 vs. 1 of 8). Combination therapy yielded additional effects in the HPAF-2 group with regard to tumor volume (-95%) and development of ascites (0 of 8 vs. 2 of 8 by A4.6.1 or BB-94 vs. 5 of 8 control mice). Both VEGF blockade and MMP inhibition reduce primary tumor size, metastasis, and angiogenesis, thereby increasing survival in experimental pancreatic cancer. Combination treatment results in additive effects in moderately differentiated HPAF-2 tumors.

Angiogenesis Inhibitors↗
PubMed2003

Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer.

BACKGROUND: We have previously reported that the glial cell-derived neurotrophic factor (GDNF) promotes pancreatic cancer cell invasion in vitro. The purpose of this study was to determine whether GDNF regulates the expression and activation of matrix metalloproteinase-9 (MMP-9) in human pancreatic cancer cells. METHODS: We used human pancreatic cancer cell line MIA PaCa-2. The effect of GDNF on mRNA and protein expression was measured by Northern blot, Western blot and enzyme-linked immunosorbent assay. MMP proteolytic activity was detected by gelatin zymography. To determine which intracellular pathways were involved, we used the following inhibitors: tyrosine kinase inhibitor Genistein, MEK-1 inhibitor PD98059 and PI3-K inhibitor Wortmannin. RESULTS: GDNF increased MMP-9 mRNA and protein expression in MIA PaCa-2 cells in a dose-dependent manner. Treatment with GDNF enhanced gelatinolytic activity of the pro and active form of MMP-9. Inhibitor experiments showed that the expression and activity of pro MMP-9 was totally inhibited by Genistein and partially by Wortmannin, whereas PD98059 had no effect. All three compounds inhibited the activity of the active form of MMP-9. CONCLUSIONS: GDNF upregulates the expression and enzymatic activity of MMP-9 through different signaling pathways in MIA PaCa-2. These findings suggest that GDNF modulates MMP-9 expression and activation, and this may promote pancreatic cancer invasion.

Culture Media↗
PubMed2003

Pancreatic neoplasms.

PURPOSE OF REVIEW: This review describes significant basic science and clinical advances in the field of pancreatic neoplasms. RECENT FINDINGS: Some of the genetic and molecular bases for the aggressive behavior of pancreatic cancer have been uncovered, and new targets for therapy have been identified. Various techniques for diagnosis and staging of this disease-endoscopic ultrasound, laparoscopy-continue to undergo evaluation. Surgical results show slightly improved long-term survival, and perioperative mortality rates remain low. The concept that locally invasive pancreatic cancer can be effectively downstaged and later resected has been called into question. Regional chemotherapy has shown promise, especially when combined with immunotherapy. Intraductal papillary mucinous tumors continue to be commonly encountered and their development and clinical course intensely studied. Acinar cell carcinomas are rare pancreatic neoplasms associated with postresection survival longer than ductal adenocarcinoma but shorter than endocrine carcinoma. Neoplasms metastatic to the pancreas can be resected safely and with improved survival compared with nonsurgical therapies. SUMMARY: The treatment of pancreatic neoplasms remains a major challenge for physicians and surgeons. Future progress requires sound scientific inquiry and continued clinical diligence.

Journal Article↗
PubMed2003

The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2.

INTRODUCTION: Selective cyclooxygenase-2 (COX-2) inhibition reduces the growth of many cancer cell lines, and this effect may be mediated through induction of apoptosis. This study was designed to investigate the effects of the COX-2 inhibitor nimesulide on the growth of human pancreatic cancer cells. METHODOLOGY: Reverse transcriptase-polymerase chain reaction analysis, northern blotting, and immunoblotting were used to demonstrate COX-2 mRNA and protein in two pancreatic cancer cell lines: BxPC-3 and MIA PaCa-2. The effect of nimesulide on cell growth was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count. Apoptosis was determined by FACS analysis, DNA laddering, and assessment of the floating cell/attached cell ratio. Caspase-3 activation was evaluated by measuring caspase-3 cellular activity and by determining the effects of two caspase inhibitors on cell viability. RESULTS: COX-2 mRNA was detected in both cell lines. Immunoblotting confirmed COX-2 protein expression in only the BxPC-3 cell line. Nimesulide decreased cell viability and inhibited cell growth in both cell lines. Incubation with 100 micromol/L nimesulide increased the fraction of apoptotic cells and the floating cell/attached cell ratio in both cell lines. DNA laddering was observed after incubation with nimesulide for 96 hours. There was no increase in caspase-3 activity within 96 hours. CONCLUSION: The selective COX-2 inhibitor nimesulide is antimitogenic in pancreatic cancer cells, which is independent of COX-2 expression. This effect in part is mediated by the induction of apoptosis.

Antineoplastic Agents↗
PubMed2003

Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer.

INTRODUCTION: The microenvironment of low oxygen that is present in human pancreatic cancer in vivo may actively influence tumor growth as well as neovascularization. AIMS: To determine whether hypoxia-inducible factor 1 (HIF-1) is specifically activated by hypoxia in vitro in pancreatic cancer cells and correlated these findings with tumor specimens. METHODOLOGY: Hypoxic regulation of vascular endothelial growth factor (VEGF) was studied by northern blot analysis and enzyme-linked immunosorbent assay. Electrophoretic mobility shift assays and western blot analysis were used to demonstrate hypoxic activation of HIF-1. The relationship between HIF-1 and VEGF in human pancreatic cancer specimens was studied by immunohistochemical analysis, northern blot analysis, and in situ hybridization. RESULTS: Studies in vivo of human pancreatic cancer tissue showed co-localization of VEGF mRNA, which is produced in ductal cancer cells, and HIF-1alpha protein, which was detectable in cell nuclei of the same cells. HIF-1alpha mRNA expression was dramatically upregulated (approximately 13-fold) in these specimens as well. In vitro, all pancreatic cancer cell lines increased VEGF production when exposed to low oxygen levels, by highly specific activation of HIF-1 DNA binding activity to the VEGF promoter. Cancer cell lines with high constitutive levels of HIF-1alpha protein were found to produce higher basal levels of VEGF. CONCLUSION: We conclude that HIF-1 is the regulatory link between tumor hypoxia and VEGF production in pancreatic cancer, thus establishing a biochemical pathway between tumor hypoxia and neoangiogenesis in this highly aggressive neoplasm.

Adenocarcinoma↗
PubMed2003

Prevention of metastatic pancreatic cancer growth in vivo by induction of apoptosis with genistein, a naturally occurring isoflavonoid.

INTRODUCTION: The critical need for novel therapeutic approaches to pancreatic cancer treatment is clear. Genistein, a naturally occurring isoflavonoid, is active against certain solid malignancies, but its effect on pancreatic cancer is unknown. AIMS: To investigate the bioactivity of genistein in experimental pancreatic cancer in vitro and in vivo. METHODOLOGY: The effect of intraperitoneal genistein administration on local tumor growth and metastatic disease was determined in an orthotopic nude mouse model. Apoptosis in tumor specimens was determined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) technique. In vitro, the effect of genistein on cell growth was assessed by cell count and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay. Apoptosis was determined in vitro by DNA laddering and annexin-V. Caspase-3 and nuclear factor-kappaB activity were measured following genistein treatment. RESULTS: In vivo, genistein significantly improved survival, almost completely inhibited metastasis, and increased apoptosis in an orthotopic model of pancreatic cancer. In vitro genistein treatment resulted in apoptosis in all pancreatic cancer cell lines tested, and this appeared to be mediated by activation of caspase-3. CONCLUSION: These findings suggest that the antimetastatic effect of genistein treatment in vivo is mediated by induction of apoptosis. Genistein may have a therapeutic benefit for patients with pancreatic cancer, in particular after surgery, to prevent recurrence of metastatic disease.

Animals↗