RESUMEN
Sacral neuromodulation (SNM) has become a standard treatment option for patients suffering from urinary urge incontinence, urgency-frequency, and/or nonobstructive urinary retention refractory to conservative and pharmacologic treatment. Since its initial development, the manufacturer of InterStim therapy (Medtronic, Inc., Minneapolis, MN, USA), has introduced technical modifications, while surgeons and researchers have adapted and published various innovations and alterations of the implantation technique. In this article, we feature our SNM technique including patient selection, comprehensive dialogue/evaluation, procedure details, and appropriate follow up. Although there is often great variability in patients with lower urinary tract dysfunction, we maintain that great success can be achieved with a systematic and methodical approach to SNM.
Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Plexo Lumbosacro , Trastornos Urinarios/terapia , Humanos , Selección de Paciente , Uretra/inervación , Vejiga Urinaria/inervaciónRESUMEN
BACKGROUND: Central to the education of future surgeons is residency which involves training and learning on patients. We examined the quality of surgical outcomes of vascular patients when residents were involved in their surgical case. STUDY DESIGN: A retrospective review was conducted using the data from the American College of Surgeons National Surgical Quality Improvement Program from the 2010 year vascular surgery patient cases. Statistical analysis was used to compare the cases with and without residents involved. RESULTS: There were a total of 363,431 from which we analyzed 2829 vascular surgery patients. Of those cases, 88% had a resident involved. Postgraduate year (PGY) 1 or 2 residents were involved in 12% and senior residents (PGY ≥ 3) were involved in 88% of surgeries. Preoperative pneumonia, cerebral vascular accident, dialysis, and smoking were significantly higher preoperative risk factors in the cases without the resident. Most of the patients were an American Society of Anesthesiology class III. Twenty-six percent of the patients were diabetic. The most common postoperative occurrences included transfusion requirement, postoperative pneumonia, and surgical site infections. Surgical site infections were the most common postoperative complication (4.6%). Cases with the resident involved had significantly more postoperative blood transfusions and on average took 15 more minutes to finish surgeries. A PGY 7 resident was predictive of prolonged hospital stay. The 30-day survival in the cases that had residents was 3.8% significantly higher compared with the cases that did not have residents. CONCLUSIONS: Resident involvement in surgeries does not significantly worsen surgical outcomes.
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Internado y Residencia , Procedimientos Quirúrgicos Vasculares/educación , Procedimientos Quirúrgicos Vasculares/normas , Competencia Clínica , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Exercise and physical activity have been linked to the prevention of certain types of cancer such as colon and breast. As prostate cancer is the most common malignancy diagnosed in the male population, there is obvious interest in determining a possible effect of exercise on disease prevention and improvement of disease-related outcomes. Thus far, data has been conflicting and there has been no clear determination of prostate cancer prevention through exercise. However, as prostate cancer treatment carries many side effects which may be bothersome and health-threatening, researchers have examined the effects of exercise training on reducing treatment-related complications and improving outcomes and quality of life (QOL). In this review, we discuss the impact of exercise on reducing side effects of prostate cancer treatment and improving cancer-specific and overall survival outcomes, as well as improving QOL in prostate cancer patients.
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Ejercicio Físico , Neoplasias de la Próstata/prevención & control , Neoplasias de la Próstata/terapia , Antagonistas de Andrógenos/efectos adversos , Humanos , Masculino , Radioterapia/efectos adversosRESUMEN
INTRODUCTION/OBJECTIVE: The degree of sexual dysfunction in patients with painful bladder syndrome (PBS) across their lifespan has not been previously documented. MATERIAL AND METHODS: The Female Sexual Function Index (FSFI) is a research tool to measure the degree of clinical female sexual dysfunction (FSD). This 19-item questionnaire evaluates FSD in six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain. This study used the FSFI with the additional variables of age, geographical location, and current medications. The participants were not blinded to the fact that this study was examining the link between PBS and FSD. Each question in the survey was targeted to a specific variable of FSD and the answers were rated on a Lickert scale. RESULTS: When compared with controls, PBS patients self-report significant sexual dysfunction in all domains evaluated by the FSFI (p < 0.001). Age-specific results were observed in regards to the domains of arousal, lubrication, and pain (p < 0.01). CONCLUSIONS: PBS patients report significant FSD in all domains when compared to controls (p < 0.001). Significant differences in the domains of arousal, lubrication, and pain exist between respondents < 30 years old and in those > 50 years of age. The extent of sexual dysfunction is worse in the areas of pain in each age group evaluated. Pain is the most significant finding in patients with FSD and PBS.
Asunto(s)
Cistitis Intersticial/complicaciones , Disfunciones Sexuales Fisiológicas/epidemiología , Sexualidad/fisiología , Adulto , Factores de Edad , Cistitis Intersticial/fisiopatología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Calidad de Vida , Factores de Riesgo , Índice de Severidad de la Enfermedad , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Fisiológicas/fisiopatología , Encuestas y CuestionariosRESUMEN
Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is found in food sources high in fiber content. IP6 has been reported to have significant inhibitory effects against a variety of primary tumors. We hypothesized that IP6 would inhibit the cell growth rate of Barrett's adenocarcinoma in vitro. Two Barrett's-associated adenocarcinoma cell lines, SEG-1 and BIC-1, were treated with IP6 at 0.5, 1.0 and 5.0 mM concentrations. Cell viability was measured by MTT assay. Apoptosis and necrosis were evaluated by the Annexin V FITC assay. Reductions (P<0.001) in cellular proliferation were observed in both cell lines. IP6 decreased late apoptosis and necrosis in BIC cells, whereas in SEG-1 cells, early apoptosis, late apoptosis and necrosis were all increased by IP6. IP6 decreases cellular growth by pro-apoptotic mechanisms. Our findings suggest that IP6 has the potential to become an effective adjunct for Barrett's adenocarcinoma. Further studies are needed to evaluate safety and clinical utility of this agent in patients with Barrett's adenocarcinoma.
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Adenocarcinoma/patología , Antineoplásicos/farmacología , Esófago de Barrett/patología , Proliferación Celular/efectos de los fármacos , Neoplasias Esofágicas/patología , Ácido Fítico/farmacología , Apoptosis , Carbohidratos/farmacología , Línea Celular Tumoral , Humanos , Masculino , Zea maysRESUMEN
BACKGROUND: We have previously demonstrated the potent in vitro antiproliferative effects of keyhole limpet hemocyanin (KLH) against melanoma. Our prior studies directed us to hypothesize that KLH would be effective in vivo against melanoma, alone and in combination with conventional immunotherapy. METHODS: Mice were inoculated with 2 x 10(7) HTB68 cells and randomized to 6 groups. Treatment groups consisted of control, KLH 200 microg, alpha interferon (AIFN) 1000 IU, interleukin-2 (IL-2) 5000 IU, KLH + AIFN, and KLH + IL-2. RESULTS: KLH + IL-2 exhibited the greatest reduction in tumor volume (30%) as compared to control (P = .014), followed by KLH + AIFN (28%, P = .031). Singly treated animals had less tumor inhibition: IL-2 (30%, P = .022), KLH (18%, not significant), and AIFN (16%, not significant). CONCLUSIONS: KLH augments the effects of AIFN, one of the standard immunotherapeutic agents against melanoma in vivo. Further in vivo and early clinical studies into the effects of KLH as both a single and combined agent are warranted.
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Adyuvantes Inmunológicos/uso terapéutico , Hemocianinas/uso terapéutico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Femenino , Interferón-alfa/uso terapéutico , Interleucina-2/uso terapéutico , Ratones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
INTRODUCTION: Pancreatic cancer is an extremely virulent form of cancer with few effective treatments. Catechin and inositol hexaphosphate (IP6), two naturally occurring molecules found in green tea and high-fiber foods, respectively, are compounds that have been shown to demonstrate anti-proliferative effects when administered as single therapeutic agents against a number of cancers. We hypothesized that, alone and in combination, IP6 and catechin would be effective against pancreatic cancer. MATERIALS AND METHODS: Pancreatic (PANC-1 and MIAPACA) cancer cell lines were cultured and treated with IP6 (0.8 mM/well), catechin (100 microM/well), and the combination of the two. Cell viability was measured by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) at 24, 48, and 72 h. Vascular endothelial growth factor (VEGF) was measured in the cell supernatants by ELISA. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC). RESULTS: The combination of catechin and IP6 significantly inhibited proliferation in the PANC-1 cell line at 24, 48, and 72 h compared to single agents (P < 0.001). Growth of the MIAPACA cell line was inhibited (P < 0.01) by each agent alone, but additive inhibitory effects were not seen. An increase in early apoptosis was attributed to catechin therapy in both cell lines (P < 0.01). The combination of these agents also increased early apoptotic activity when compared to the control (P < 0.001). IP6 reduced VEGF in both cell lines (P < 0.01). In combination, catechin and IP6 amplified VEGF reduction compared to each agent in MIAPACA and control (P < 0.002). CONCLUSIONS: These results, combined with the prevalence of these compounds in safe, naturally occurring foods, make catechin and IP6 attractive therapies for treatment, and possibly in preventative trials, of pancreatic cancer.
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Catequina/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Pancreáticas/patología , Ácido Fítico/farmacología , Apoptosis/efectos de los fármacos , Catequina/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Necrosis , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/prevención & control , Ácido Fítico/uso terapéutico , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
INTRODUCTION: Our hypothesis was that keyhole limpet hemocyanin (KLH) would augment the effects of standard immunotherapies for melanoma including interferon-alpha (AIFN) and interleukin (IL)-2. METHODS: The HTB68 melanoma cell line was treated with KLH, AIFN, and IL-2 as single and combined agents. Cell viability, apoptotic activity, and vascular endothelial growth factor levels were all evaluated. RESULTS: Cell growth was reduced with KLH (28%), AIFN (54%), and IL-2 (29%) (all P < .001). KLH and IL-2 combined exhibited a 47% inhibition of cell growth, whereas KLH and AIFN combined yielded a 67% reduction in cell growth (both P < .001). KLH and AIFN combined significantly increased both early (10%) and late (14%) apoptotic activity compared with controls (5% and 7%, P < .001). CONCLUSIONS: The additive effects exhibited by the combination of KLH with AIFN or IL-2 are encouraging and support combination therapy as an effective treatment for this aggressive disease.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Supervivencia Celular/efectos de los fármacos , Hemocianinas/farmacología , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Adyuvantes Inmunológicos/uso terapéutico , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Hemocianinas/uso terapéutico , Humanos , Inmunoterapia , Interferón-alfa/uso terapéutico , Interleucina-2/uso terapéutico , Melanoma/metabolismo , Neoplasias Cutáneas/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
We hypothesized that combined treatment with Cox-1 and Cox-2 specific inhibitiors would exhibit synergistic effects against breast cancer in vitro. Two human breast cancer cell lines (HTB26, MCF-7) were treated with catechin (Cox-1 inhibitor) or NS398 (Cox-2 inhibitor) at 100 microM as both single and combined treatments. Reductions in cell growth were observed in both cell lines at 24 and 72 h in both single and combined treatments (p<0.001). Combined treatment produced a significantly greater inhibition as compared to single agents alone. Upon cell cycle evaluation, Cox-1 and -2 antagonism increased G1 and G2 phase fractions in MCF-7 cells (p<0.001 and p<0.05 respectively). No additive changes were observed when the two agents were combined. An increase in the G2 phase was observed in the HTB26 cells when treated with NS398 alone (p<0.001). However, a decrease in the S-phase was observed when these cells were treated with NS398, as a single agent (p<0.01) or when the two agents were combined (p<0.01). The significant and additive effects exhibited by the combination of Cox-1 and -2 inhibitors and their effects on cell cycle suggest that these agents could become an effective treatment modality for carcinoma of the breast.
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Neoplasias de la Mama/enzimología , Ciclooxigenasa 1/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Proteínas de la Membrana/antagonistas & inhibidores , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclooxigenasa 2 , Sinergismo Farmacológico , Femenino , HumanosRESUMEN
BACKGROUND: Cytokine activation in the pancreatitis induces local and systemic cellular damage. Transcription factors interferon regulatory factor-1 (IRF-1) and the tumor suppressor gene p53 collaborate to enhance p21 related cell cycle regulation during pathological disease progression. However, little is known about their role in the pancreas after cytokine challenge. Our laboratory has previously shown that TNF-alpha induces the binding of many transcription factors, including NF-kappa B, and treatment with the gut hormone, Peptide YY (PYY), ameliorates the effects. We hypothesized that TNF-alpha would induce IRF-1 and p53 protein binding in pancreatic acinar cells and that PYY would attenuate the effect. MATERIALS AND METHODS: Rat pancreatic acinar AR42J cells were treated with rat recombinant TNF-alpha (200 ng/ml). To verify that our model was inducing pancreatitis, alpha-amylase activity was measured in the cell culture supernatant by fluorescence spectroscopy. PYY [3-36] was added at 500 pM 30 min post-TNF treatment; cells were harvested at 2 h for extraction of nuclear protein. Transcription factor binding of IRF-1 and p53 were determined by protein/DNA array analysis using chemiluminescence detection, and relative spot densities were measured by densitometry. A two-fold increase or decrease in density was considered significant. RESULTS: Amylase enzyme activity was significantly (P < 0.05) elevated in the TNF-alpha-treated cells by 2 h. Protein/DNA array analysis revealed significant up-regulation of both IRF-1 and p53 protein in nuclear extracts. Induction by TNF-alpha increased IRF-1 protein binding 3.5-fold, while binding levels of p53 protein increased six-fold. The addition of PYY to TNF-treated cells reduced IRF-1 and p53 binding to control levels. CONCLUSIONS: We have shown for the first time that short-term exposure to TNF-alpha induces the binding activity of transcription factors IRF-1 and p53 in rat pancreatic acinar cells, and that addition of PYY reduces it. Regulation of transcription factor activity by PYY may have therapeutic potential in altering the progression of pancreatitis.
Asunto(s)
Factor 1 Regulador del Interferón/metabolismo , Páncreas Exocrino/metabolismo , Péptido YY/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Enfermedad Aguda , Amilasas/metabolismo , Animales , Línea Celular , Factor 1 Regulador del Interferón/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Páncreas Exocrino/citología , Páncreas Exocrino/efectos de los fármacos , Pancreatitis/metabolismo , Péptido YY/farmacología , Unión Proteica/efectos de los fármacos , Ratas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Inositol Hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate found in food sources high in fiber content. We have previously reported IP6 to have significant inhibitory effects against pancreatic cancer in vitro. We hypothesized that the IP6 would significantly inhibit cell growth of cutaneous melanoma in vitro. MATERIALS AND METHODS: The melanoma line HTB68 was cultured using standard techniques and treated with IP6 at doses ranging from 0.2 to 1.0 mM/well. Cell viability was measured by MTT at 72 h. VEGF production was measured in the cell supernatants by ELISA. Apoptosis was evaluated by Annexin V-FITC and results calculated using FACS analysis. Statistical analysis was performed by ANOVA. RESULTS: Significant reductions (P < 0.001) in cellular proliferation were observed with IP6. Overall, IP6 exhibited a mean inhibition of cell growth of 52.1 +/- 11.5% (range, 1.6-83.0%) at 72 h of incubation. VEGF production was significantly reduced (P < 0.001) by the addition of IP6 (7.5 pg/ml) compared to control (40.9 pg/ml). IP6 significantly increased (P = 0.029) late apoptosis from 5.3 to 7.0% gated events. No changes in necrosis or early apoptosis were observed. CONCLUSIONS: Adjuvant treatment of melanoma continues to challenge clinicians and patients. Our findings that IP6 significantly decreased cellular growth, VEGF production and increased late apoptosis in melanoma suggest its potential therapeutic value. Further in vivo studies are planned to evaluate safety and clinical utility of this agent.
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Proliferación Celular/efectos de los fármacos , Melanoma/tratamiento farmacológico , Ácido Fítico/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Humanos , Melanoma/metabolismo , Melanoma/patología , Ácido Fítico/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: We hypothesized that keyhole limpet hemocyanin (KLH) would reduce cellular proliferation and effect apoptosis of melanoma cell lines in vitro. METHODS: Two human melanoma cell lines (HTB68 and HTB72) were subjected to a dose-response treatment regimen of KLH (0.4 microg to 100 microg/well). Cell viability was tested by MTT assay (SIGMA, St Louis, MO) at 72 hours. Apoptosis and necrosis were measured by the Annexin V FITC assay (Biovision Inc, Mountain View, CA). RESULTS: Melanoma cell proliferation was significantly reduced in the HTB68 cell line treated with 6.3 microg or higher doses of KLH. A significant reduction in cell growth was also observed in the HTB72 cells at 50 and 100 microg of KLH. KLH increased early apoptotic activity, whereas both late apoptosis and necrosis were decreased by the addition of KLH. CONCLUSIONS: KLH significantly reduces cellular proliferation in vitro in melanoma, via early apoptotic pathways. The results warrant in vivo studies into the effects of KLH in melanoma.
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Apoptosis/fisiología , Proliferación Celular/efectos de los fármacos , Hemocianinas/farmacología , Melanoma/patología , Moluscos , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , Técnicas In Vitro , Melanoma/tratamiento farmacológicoRESUMEN
BACKGROUND: Esophageal adenocarcinoma often arises from Barrett's esophagus. Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) play critical roles in cell survival. We hypothesized that inhibition of these pathways in Barrett's adenocarcinoma would decrease cell proliferation and alter apoptosis in vitro. MATERIALS AND METHODS: Two Barrett's-associated adenocarcinoma cell lines, SEG-1 (wild-type p53) and BIC-1 (mutant p53), were treated with MAPK (U0126) and PI3K (LY294002) inhibitors at 20 microm concentrations. After 24 and 72 h, cell viability was measured by MTT assay. Apoptosis and necrosis were evaluated by the Annexin V-FITC assay. Statistical analysis was performed by ANOVA. RESULTS: LY294002 and U0126 treatment produced significant reductions (range 15.7 to 62.0%, P < 0.05) in cellular proliferation at both 24 and 72 h in the SEG-1 cells. BIC-1 cell viability was reduced (39.3 to 56.4%, P < 0.05) at 72 h. Both early and late apoptotic activity were significantly increased (P < 0.05) in the SEG-1 cells using both inhibitors. Necrosis was significantly reduced (P < 0.05) using both inhibitors. No changes in either early or late apoptosis or necrosis were observed in the BIC-1 cells. CONCLUSIONS: Herein, we report significant antiproliferative effects against Barrett's adenocarcinoma by MAPK and PI3K inhibition in vitro. Pro-apoptotic mechanisms prevail in the wild-type p53 cells. Further investigation is warranted to advance the clinical treatment of this devastating disease.
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Esófago de Barrett/patología , Butadienos/farmacología , Cromonas/farmacología , Inhibidores Enzimáticos/farmacología , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Morfolinas/farmacología , Nitrilos/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Adenocarcinoma , Apoptosis/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias Esofágicas , Humanos , NecrosisRESUMEN
BACKGROUND: We have previously shown the inhibitory effects of keyhole limpet hemocyanin (KLH) against breast and pancreatic cancer in vitro. We hypothesize that its actions in breast and pancreas cancer cells are via apoptotic or cytokine pathways. METHODS: Two breast cancer cell lines, ZR75-1 and MCF-7, and one pancreas cancer cell line, PANC-1, were treated with KLH at 500 mug, 250 mug, and 250 ng/mL. Cell viability, cytokine production, and apoptosis were measured. RESULTS: Significant growth inhibition was observed in all cell lines at all KLH concentrations tested. Significant changes in cytokine production were observed in all cell lines. An increase in early and late apoptotic activity was observed in the MCF-7, whereas a reduction in late apoptotic activity was observed in the ZR75-1 cells. CONCLUSIONS: KLH directly inhibits the growth of human breast and pancreas cancer in vitro by apoptotic and nonapoptotic mechanisms.
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Adyuvantes Inmunológicos/farmacología , Neoplasias de la Mama/metabolismo , Hemocianinas/farmacología , Neoplasias Pancreáticas/metabolismo , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/prevención & control , Línea Celular Tumoral , Femenino , Humanos , Técnicas In Vitro , Interleucinas/metabolismo , Masculino , Neoplasias Pancreáticas/prevención & control , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate found in food sources high in fiber content. IP6 has been reported to have significant inhibitory effects against a variety of primary tumors including breast and colon. The effects of IP6 have not been evaluated in pancreatic cancer. We hypothesized that IP6 would significantly inhibit cell growth and increase the apoptotic rate of pancreatic cancer in vitro. MATERIALS AND METHODS: Two pancreatic cancer cell lines (MIAPACA and PANC1) were cultured using standard techniques and treated with IP6 at doses of 0.5, 1.0, and 5.0 mm. Cell viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated by Annexin V-FITC and results calculated using FACS analysis. Statistical analysis was performed by ANOVA. RESULTS: Significant reductions (P < 0.01) in cellular proliferation were observed with all IP6 concentrations tested in both cell lines and at both time points. Reductions in cell proliferation ranged from 37.1 to 91.5%. IP6 increased early and late apoptotic activity (P < 0.01). CONCLUSIONS: Treatment of pancreatic cancer with the common dietary polyphosphorylated carbohydrate IP6 significantly decreased cellular growth and increased apoptosis. Our findings suggest that IP6 has the potential to become an effective adjunct for pancreatic cancer treatment. Further in vivo and human studies are needed to evaluate safety and clinical utility of this agent in patients with pancreatic cancer.
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Adenocarcinoma/patología , Adenocarcinoma/fisiopatología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/fisiopatología , Ácido Fítico/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Oryza/química , Ácido Fítico/aislamiento & purificación , Zea mays/químicaRESUMEN
BACKGROUND: We hypothesized that combined treatment with cyclooxygenase (Cox)-1 (catechin) and Cox-2 (NS398)-specific inhibitors would reduce cellular proliferation synergistically in genitourinary cancer. METHODS: Bladder (T24 and TCCSUP) and prostate (DU145, LnCaP, and PC3) cancer cell lines were treated with catechin and NS398 at a dose of 100 mumol/L as single and combined treatments. Viability was measured by MTT assay at 24 and 72 hours. RESULTS: Significant synergism of Cox-1 and Cox-2 inhibitors was observed in both bladder cancer lines at both 24 and 72 hours. Synergism of Cox-1 and -2 inhibitors also was noted in the DU145 cells at 72 hours, LnCap cells at 24 hours, and PC3 at both 24 and 72 hours. CONCLUSIONS: Significant synergistic effects exhibited by the combination of Cox-1 and Cox-2 inhibitors suggest that these could become a highly effective treatment modality for carcinoma of both the bladder and prostate.
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Apoptosis/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/farmacología , Isoenzimas/efectos de los fármacos , Prostaglandina-Endoperóxido Sintasas/efectos de los fármacos , Análisis de Varianza , Proliferación Celular/efectos de los fármacos , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Sinergismo Farmacológico , Humanos , Técnicas In Vitro , Masculino , Proteínas de la Membrana , Probabilidad , Neoplasias de la Próstata/patología , Sensibilidad y Especificidad , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Peptide YY (PYY) is an endogenous gut hormone that inhibits the growth of certain cancers. Adenocarcinoma of the esophagus usually arises from Barrett's esophagus. We hypothesized that treatment of Barrett's adenocarcinoma with PYY would result in decreased proliferation. METHODS: Barrett's cancer cell lines (BIC and SEG-1) were treated with PYY (3-36) at 500 pmol/mL. Viability was measured by MTT at 24 and 72 hours. Apoptosis and necrosis was evaluated by flow cytometry. RESULTS: PYY reduced proliferation in SEG-1 cells at 24 hours (21.2% +/- 3.4%, P <0.001) and 72 hours (14.2% +/- 6.2%, P <0.001). In the BIC cells, growth was inhibited by 7.9% +/- 7.0%, P = 0.021 after 72 hours. PYY increased late apoptotic activity in SEG-1 cells by 31%, P = 0.014. CONCLUSIONS: This is the first report of antiproliferative effects of PYY against Barrett's carcinoma in vitro. Reductions in cell growth appear to be mediated by proapoptotic mechanisms. Further investigation of PYY in the treatment of Barrett's adenocarcinoma is warranted.
Asunto(s)
Adenocarcinoma/patología , Apoptosis/efectos de los fármacos , Esófago de Barrett/patología , Proliferación Celular/efectos de los fármacos , Neoplasias Esofágicas/patología , Péptido YY/farmacología , Análisis de Varianza , Humanos , Técnicas In Vitro , Probabilidad , Factores de Riesgo , Sensibilidad y Especificidad , Células Tumorales CultivadasRESUMEN
BACKGROUND: Pentosan polysulfate (Elmiron); (Alza Pharmaceuticals, Mountain View, CA) is the only Food and Drug Administration-approved oral therapy for interstitial cystitis (IC). Women with IC and breast cancer are often in the same age range; therefore, we hypothesize that pentosan polysulfate may also have a therapeutic effect on breast cancer cells in vitro. METHODS: Breast cancer lines MCF-7, ZR75-1, and HTB26 were treated with pentosan polysulfate at various concentrations. Cell viability was measured at 24 hours by MTT. Annexin V assay was used to determine the effect of pentosan polysulfate on apoptotic and necrotic activity. RESULTS: Pentosan polysulfate significantly inhibited the growth of the ZR75-1 cells; however, significant cellular proliferation was observed in the MCF-7 cells. A significant change in late apoptotic activity was observed with pentosan polysulfate treatment in vitro. CONCLUSIONS: Caution should be used in prescribing pentosan polysulfate for the treatment of IC in patients who are both in high-risk groups for breast cancer and premenopausal females.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Poliéster Pentosan Sulfúrico/farmacología , Análisis de Varianza , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Técnicas In Vitro , Probabilidad , Factores de Riesgo , Sensibilidad y Especificidad , Células Tumorales CultivadasRESUMEN
To test our hypothesis that Cyclooyxgenase-2 (COX-2) inhibitors would stop the growth of breast and prostate cancer cells in vitro, two breast (MCF-7, ZR75-1) and two prostate cancer cell lines (PC-3, DU145) were treated with rofecoxib (Vioxx) or NS398. Cell growth was measured by MTT at 24 and 72 hours. Statistical analysis was performed by ANOVA. Significant growth inhibition (p < 0.05) was observed in all cell lines in a dose-dependent manner after treatment with COX-2 inhibitors. Rofecoxib inhibited cellular proliferation by inducing (p < 0.001) apoptosis in breast cancer cells. Our study indicates that COX-2 inhibition reduces the growth of human breast and prostate cancer in vitro. Human studies are needed to evaluate the clinical utility of rofecoxib treatment in breast or prostate cancers.
Asunto(s)
Isoenzimas/antagonistas & inhibidores , Lactonas/farmacología , Nitrobencenos/farmacología , Sulfonamidas/farmacología , Apoptosis , Neoplasias de la Mama , División Celular/efectos de los fármacos , Línea Celular Tumoral , Ciclooxigenasa 2 , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Proteínas de la Membrana , Prostaglandina-Endoperóxido Sintasas , Neoplasias de la Próstata , SulfonasRESUMEN
BACKGROUND: The incidence of Barrett's adenocarcinoma has increased dramatically in the United States, whereas squamous cell carcinoma of the esophagus remains a worldwide problem. Cyclooxygenase (COX)-2 may play an important role in gastrointestinal carcinogenesis and is overexpressed in both Barrett's metaplasia and adenocarcinoma. We hypothesized that a selective and commercially available COX-2 inhibitor, rofecoxib (Vioxx), would inhibit growth of Barrett's adenocarcinoma and squamous cell carcinoma of the esophagus by apoptotic pathways. Additional comparison studies were performed with commercially available COX-2 and COX-1 inhibitors. MATERIALS AND METHODS: Two esophageal adenocarcinoma cell lines (SEG-1 and BIC) and two esophageal squamous cell cancer lines (KYSE 150 and KYSE 410) were treated with rofecoxib at doses ranging from 8.0 to 125 microg/well. NS-398 (a COX-2 antagonist) and Catechin (a COX-1 antagonist) were also used at doses of 50 and 100 microM. Esophageal cell viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated after 18 h of incubation with rofecoxib, NS398, and Catechin by flow cytometry via annexin V assay. RESULTS: Rofecoxib, NS-398, and Catechin treatments all resulted in significant antiproliferative effects in both adenocarcinoma and squamous cell carcinoma of the esophagus in vitro. Substantial increases in apoptotic activity were also found in all cell lines. CONCLUSIONS: Our findings suggest that COX-2 and COX-1 inhibition has potential to become an effective treatment for both histological variants of esophageal cancer. Further in vivo and human studies are warranted to evaluate the safety and clinical utility of these agents in patients with all cancers of the esophagus.