[Pancreatic Acinar Cell Carcinoma with Peritoneal Recurrence Treated with Peritonectomy and Intraoperative Hyperthermic Intraperitoneal Chemotherapy-A Case Report].

A 31-year-old man with a big epigastric mass from pancreas body was completely removed by distal pancreatectomy and segmental gastrectomy. Two years after oral administration of S-1 for 4 courses, peritoneal dissemination on the right subdiaphragmatic space was detected. Laparotomy revealed white colored round nodules were found scattered on the peritoneal surface, and the peritoneal cancer index(PCI)was 18. To achieve complete resection of peritoneal nodules, peritonectomy was performed. After complete removal of macroscopic peritoneal metastasis(PM), intraoperative hyperthermic intraoperative peritoneal chemotherapy using 1 gr of gemcitabine and 60 mg of docetaxel was performed for 40 min with thermal dose of 41.5 min. Postoperative course was uneventful. Drug sensitivity test(HDRA method)showed that gemcitabine that gemcitabine showed the highest inhibition rate. The patient was treated with systemic gemcitabine chemotherapy. He is still alive without recurrence 18 months after peritonectomy plus intraoperative HIPEC. Pathological examination showed pancreatic acinar cell carcinoma(PACC)demonstrating positive for chymotrypsin. In conclusion, we present a PACC-case with PM successfully treated by a comprehensive treatment. Intraoperative HIPEC using gemcitabine may be effective for PACC patients with PM in treating residual micrometastasis after peritonectomy.

OBP-401-GFP telomerase-dependent adenovirus illuminates and kills high-metastatic more effectively than low-metastatic triple-negative breast cancer in vitro.

We previously described the development of a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of MDA-MB-231 human breast cancer in nude mice. The isolated variant is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared with 2 of 12 of the parental cell line. OBP-401 is a telomerase-dependent cancer-specific, green fluorescent protein (GFP)-expressing adenovirus. OBP-401 was used to infect parental MDA-MB-231P cells and high-metastatic MDA-MB-231H and MDA-MB-231HLN isolated from a lymph node metastasis and MDA-MB-231HLM isolated from a lung metastasis. Time-course imaging showed that OBP-401 labeled MDA-MB-231HP, MDA-MB-231HLN, and MDA-MB-231HLM cells more brightly than MDA-MB-231 parental cells. OBP-401 killed MDA-MB-231H, MDA-MB-231HLN, and MDA-MB-231HLM cells more efficiently than MDA-MB-231P parental cells. These results indicate that OBP-401 could infect, label and then kill high-metastatic MDA-MB-231 more efficiently than low-metastatic MDA-MB-231.

Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery.

Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. To achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 was used to label the cancer cells of a pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery or single-color FGS could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant-cancer surgery.

Bone complications among prostate cancer survivors: long-term follow-up from the prostate cancer outcomes study.

BACKGROUND: To assess the relationship between androgen deprivation therapy (ADT) exposure and self-reported bone complications among men in a population-based cohort of prostate cancer survivors followed for 15 years after diagnosis. METHODS: The Prostate Cancer Outcomes Study enrolled 3533 patients diagnosed with prostate cancer between 1994 and 1995. This analysis included participants with non-metastatic disease at the time of diagnosis who completed 15-year follow-up surveys to report development of fracture, and use of bone-related medications. The relationship between ADT duration and bone complications was assessed using multivariable logistic regression models. RESULTS: Among 961 surviving men, 157 (16.3%) received prolonged ADT (>1 year), 120 (12.5%) received short-term ADT (⩽ 1 year) and 684 (71.2%) did not receive ADT. Men receiving prolonged ADT had higher odds of fracture (OR 2.5; 95% confidence interval (CI): 1.1-5.7), bone mineral density testing (OR 5.9; 95% CI: 3.0-12) and bone medication use (OR 4.3; 95% CI: 2.3-8.0) than untreated men. Men receiving short-term ADT reported rates of fracture similar to untreated men. Half of men treated with prolonged ADT reported bone medication use. CONCLUSIONS: In this population-based cohort study with long-term follow-up, prolonged ADT use was associated with substantial risks of fracture, whereas short-term use was not. This information should be considered when weighing the advantages and disadvantages of ADT in men with prostate cancer.

Suppression of tumor angiogenesis by targeting the protein neddylation pathway.

Inhibition of protein neddylation, particularly cullin neddylation, has emerged as a promising anticancer strategy, as evidenced by the antitumor activity in preclinical studies of the Nedd8-activating enzyme (NAE) inhibitor MLN4924. This small molecule can block the protein neddylation pathway and is now in clinical trials. We and others have previously shown that the antitumor activity of MLN4924 is mediated by its ability to induce apoptosis, autophagy and senescence in a cell context-dependent manner. However, whether MLN4924 has any effect on tumor angiogenesis remains unexplored. Here we report that MLN4924 inhibits angiogenesis in various in vitro and in vivo models, leading to the suppression of tumor growth and metastasis in highly malignant pancreatic cancer, indicating that blockage of angiogenesis is yet another mechanism contributing to its antitumor activity. At the molecular level, MLN4924 inhibits Cullin-RING E3 ligases (CRLs) by cullin deneddylation, causing accumulation of RhoA at an early stage to impair angiogenic activity of vascular endothelial cells and subsequently DNA damage response, cell cycle arrest and apoptosis due to accumulation of other tumor-suppressive substrates of CRLs. Furthermore, we showed that inactivation of CRLs, via small interfering RNA (siRNA) silencing of its essential subunit ROC1/RBX1, recapitulates the antiangiogenic effect of MLN4924. Taken together, our study demonstrates a previously unrecognized role of neddylation in the regulation of tumor angiogenesis using both pharmaceutical and genetic approaches, and provides proof of concept evidence for future development of neddylation inhibitors (such as MLN4924) as a novel class of antiangiogenic agents.

This is My Story: participatory performance for HIV and AIDS education at the University of Malawi.

University students represent a subset of young men and women at risk for HIV in high prevalence settings. Innovative programs are needed to raise awareness on the unique issues around HIV and AIDS in the university campus, while training student leaders for peer-based education. The Process and Collaboration for Empowerment and Discussion (PACED) method engages artists and people living with HIV and AIDS (PLWHA) to create a performance that encourages community dialog about HIV and AIDS and empowers PLWHA. 'This is My Story' was a program at the University of Malawi, Chancellor College, which adapted the PACED approach for university students. A qualitative evaluation conducted 1 year later among students and PLWHA participants and audience members demonstrated retention of the following themes: (i) trust in a relationship and how it affects women,(ii) equality for PLWHA and (iii) life after HIV and AIDS. All of the PLWHA and 90.9% of student participants reported a greater sense of empowerment. Of the audience members, 82.1% discussed the performance with friends and family. We thus present the PACED approach as a valuable tool in HIV and AIDS education and prevention among university students in Malawi.

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

BACKGROUND: Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). METHODS: The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. RESULTS: A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. CONCLUSIONS: Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium.

OBJECTIVE: Spinal cord tumours are highly malignant and often lead to paralysis and death due to their infiltrative nature, high recurrence rate and limited treatment options. In this study, we measured antitumour efficacy of the Salmonella typhimurium A1-R tumour-targeting bacterium strain, administered systemically or intrathecally, to spinal cord cancer in orthotopic mouse models. MATERIALS AND METHODS: Tumour fragments of U87-RFP were implanted by surgical orthotopic implantation into the dorsal site of the spinal cord. Five and 10 days after transplantation, eight mice in each group were treated with A1-R (2 x 10(7) CFU/200 microL i.v. injection or 2 x 10(6) CFU/10 microL intrathecal injection). RESULTS: Untreated mice showed progressive paralysis beginning at day 6 after tumour transplantation and developed complete paralysis between 18 and 25 days. Mice treated i.v. with A1-R had onset of paralysis at approximately 11 days and at 30 days; five mice developed complete paralysis, while the other three mice had partial paralysis. Mice treated by intrathecal injection of A1-R had onset of paralysis at approximately 18 days and one mouse was still not paralysed at day 30. Only one mouse developed complete paralysis at day 30 in this group. Intrathecally treated animals had a significantly better survival than the i.v. treated group as well as over the control group. CONCLUSIONS: These results suggest that S. typhimurium A1-R monotherapy can effectively treat spinal cord glioma.

Clinically-relevent orthotopic metastatic models of pancreatic cancer imageable with fluorescent genetic reporters.

This article describes authors' cumulative experience with the development and preclinical application of clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer made imageable with genetic reporters. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of green fluorescent protein (GFP) or red fluorescent protein (RFP). Tumors with fluorescent genetic reporters are established subcutaneously in nude mice, and fragments of the subcutaneous tumors are then surgically transplanted onto the pancreas. Loco-regional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdo-men in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time quantitative fluorescence imaging of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. A high correlation between florescence optical imaging, magnetic resonance imaging, and ultrasound in these models has been demonstrated. Transplantation of RFP-expressing tumor fragments onto the pancreas of GFP- or cyan fluorescent protein-expressing transgenic mice was used to facilitate visualization of tumor-host interaction between the pancreatic cancer cells and host-derived stroma and vasculature. Such in vivo models have enabled visualization in real time and acquisition of images of the progression of pancreatic cancer in the live animal, the models also demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate metastatic human pancreatic cancer and novel therapeutic strategies directed against it.

Variable stiffness colonoscope versus regular adult colonoscope: meta-analysis of randomized controlled trials.

BACKGROUND AND STUDY AIMS: The variable stiffness colonoscope (VSC) may have theoretical advantages over standard adult colonoscopes (SACs), though data are conflicting. We conducted a meta-analysis to compare the efficacies of the VSC and SAC. STUDY DESIGN: We searched Medline (1966 - 2008) and abstracts of gastroenterology scientific meetings in the 5 years to February 2008, only for randomized clinical trials (RCTs) of adult patients. Trial quality was assessed using the Delphi list. In a meta-analysis with a fixed effects model, cecal intubation rates, cecal intubation times, abdominal pain scores, sedation used, and use of ancillary maneuvers, were compared in separate analyses, using weighted mean differences (WMDs), standardized mean differences (SMDs), or odds ratios (ORs). RESULTS: Seven RCTs satisfied the inclusion criteria (1923 patients), four comparing VSC with SAC procedures in adults, and three evaluating the pediatric VSC. There was no significant heterogeneity among the studies. The overall trial quality was adequate. Cecal intubation rate was higher with the use of VSC (OR = 2.08, 95 % confidence interval [CI] 1.29 to 3.36). The VSC was associated with lower abdominal pain scores and a decreased need for sedation during colonoscopy. Cecal intubation time was similar for the two colonscope types (WMD = - 0.21 minutes, 95 % CI - 0.85 to 0.43). Because of the nature of the intervention no studies were blinded. There was no universal method for using the VSC. CONCLUSIONS: Compared with the SAC, VSC use was associated with a higher cecal intubation rate, less abdominal pain, and decreased need for sedation. However, cecal intubation times were similar for the two colonoscope types.

A color-coded orthotopic nude-mouse treatment model of brain-metastatic paralyzing spinal cord cancer that induces angiogenesis and neurogenesis.

OBJECTIVE: Cancer of the spinal cord is highly malignant and often leads to paralysis and death. A realistic mouse model would be an important benefit for the better understanding and treatment of spinal cord glioma. MATERIALS AND METHODS: To develop an imageable, patient-like model of this disease, U87 human glioma tumour fragments (expressing red fluorescent protein), were transplanted by surgical orthotopic implantation into the spinal cord of nontransgenic nude mice or transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). In ND-GFP mice, GFP is expressed in nascent blood vessels and neural stem cells. The animals were treated with temozolomide or vehicle control. RESULTS: The intramedullary spinal cord tumour grew at the primary site, caused hind-limb paralysis and also metastasized to the brain. Temozolomide inhibited tumour growth (P<0.01) and prevented metastasis, as well as prevented paralysis in four mice and delayed paralysis in two mice of the six tested (P=0.005). In the ND-GFP-expressing host, ND-GFP cells staining positively for neuronal class III-beta-tubulin or CD31, surrounded the tumour. These results suggest that the tumour stimulated both neurogenesis and angiogenesis, respectively. CONCLUSION: A patient-like model of spinal cord glioma was thus developed, which can be used for the discovery of new agents, including those that inhibit invasion and metastasis of the disease as well as those that prevent paralysis.

Effect of a single dose of dexamethasone on glucose homeostasis in healthy horses by using the combined intravenous glucose and insulin test.

Sustained dexamethasone administration to horses results in insulin resistance, which may predispose them to laminitis. A single dose of dexamethasone is commonly used as a diagnostic aid, yet the effect of a single dose of dexamethasone on glucose homeostasis in horses is not well defined. The objective of this study was to characterize the change in glucose dynamics over time in response to a single dose of dexamethasone. A combined glucose-insulin tolerance test (CGIT) was performed on 6 adult geldings before and at 2, 24, and 72 h postdexamethasone (40 microg/kg of BW, i.v.); a minimum of 1 wk of rest was allowed between treatments. Before any treatment, the CGIT resulted in a hyperglycemic phase followed by a hypoglycemic phase. Dexamethasone affected glucose dynamics in 3 ways: 1) at 2 h, dexamethasone shortened the ascending branch of the negative phase (P < 0.001) of the test, indicating moderate insulin resistance; 2) at 24 h, dexamethasone impaired glucose clearance by extending the positive phase and eliminating the negative phase while insulin was elevated before the CGIT, indicating a decreased response to insulin; and 3) at 72 h, dexamethasone caused a deeper nadir value (P < 0.001) compared with predexamethasone, indicating an increased response to insulin. It was concluded that dexamethasone decreased the response to insulin as early as 2 h and maximally at 24 h. At 72 h, dexamethasone caused an increased response to insulin, which was unexpected.

Kidney function after solitary pancreas transplantation.

Preserving kidney function in patients after solitary pancreas transplantation (SPTx) is an important consideration, yet various factors may negatively impact long-term function of the native kidneys or kidney allograft. To determine changes in kidney function over time in a series of patients receiving SPTx, we conducted a retrospective analysis and tracked changes in serum creatinine (SCr) and calculated glomerular filtration rate (GFR) from baseline to 6 months, 1 year, or 3 years after SPTx in a series of pancreas after kidney transplants PAK; (n = 61) and pancreas transplants alone PTA; (n = 27) performed at our institution. The mean follow-up for the PAK and PTA groups was 3.4 and 2.7 years, respectively. In this series, 8% of patients after SPTx developed significant kidney failure, defined by either initiation of dialysis or receiving a kidney transplant (PAK-6, PTA-1). Twenty seven percent of SPTx patients with a baseline GFR < 60 suffered either an elevated SCr > 2.2, dialysis, or kidney transplant, whereas no patients with a baseline GFR > 60 developed significant kidney dysfunction. In the PAK group, the GFR did not show significant deterioration over time. In contrast to relatively stable kidney function in PAK patients, PTA patients experienced overall significantly greater rates of decline over time. GFR in PTA patients decreased from 78 +/- 19 (40 to 114) mL/min/1.73 m2 at baseline to 65 +/- 20 at 1 year (P = .006), while SCr increased from 1.03 +/- 0.25 mg/dL to 1.28 +/- 0.43 over the same time period (P = .012). These data show that kidney function may deteriorate after SPTx and proper patient selection may reduce the frequency of this complication.

Imaging of cell trafficking and metastases of paediatric rhabdomyosarcoma.

OBJECTIVE: The aim of this study was to establish a preclinical mouse model to study metastases of paediatric rhabdomyosarcoma at the macroscopic and cellular levels, with different imaging methods. EXPERIMENTAL DESIGN: The alveolar rhabdomyosarcoma cell line Rh30 was stably transfected with the red fluorescent protein (DsRed2) then was xenotransplanted (intravenous injection [n = 8], and footpad injection [n = 8]) into nude mice (NMRI nu/nu). Macroscopic imaging of metastases was performed using DsRed2-fluorescence and flat-panel volumetric computed tomography scan. In a further series of animals (n = 8), in vivo cell trafficking of rhabdomyosarcoma cells using cellular imaging with an Olympus OV100 variable-magnification small-animal imaging system was used. RESULTS: Metastases in the pelvis, thoracic wall and skin were visualized by fluorescence imaging. Pelvic metastases were found after tail vein injection and at other metastatic sites after footpad injection. Flat-panel volumetric computed tomography scan data allowed highly specific analysis of contrast between tumour and surrounding tissue. Correlation between fluorescence and flat-panel volumetric computed tomography scan imaging data was observed. Single-cell imaging visualized tumour cells in the vessels and demonstrated the arrest of tumour cells at vessel junctions followed by extravasation of the tumour cells. CONCLUSION: We established a model for visualization of experimental metastatic invasion and describe relevant tools for imaging childhood rhabdomyosarcoma metastases at the macroscopic and cellular levels. Imaging of cell trafficking visualized the behaviour of tumour cells and development of metastases by accumulation and extravasation of rhabdomyosarcoma cells.

Microwave thermotherapy for benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold-standard treatment for alleviating urinary symptoms and improving urinary flow in men with symptomatic benign prostatic hyperplasia (BPH). However, the morbidity of TURP approaches 20%, and less invasive techniques have been developed for treating BPH. Preliminary data suggest that microwave thermotherapy, which delivers microwave energy to produce coagulation necrosis in prostatic tissue, is a safe, effective treatment for BPH. OBJECTIVES: To assess the therapeutic efficacy and safety of microwave thermotherapy techniques for treating men with symptomatic benign prostatic obstruction. SEARCH STRATEGY: Randomized controlled trials were identified from the Cochrane Collaboration Library, MEDLINE, EMBASE, bibliographies of retrieved articles and reviews, and by contacting expert relevant trialists and microwave manufacturers. SELECTION CRITERIA: All randomized controlled trials evaluating transurethral microwave thermotherapy (TUMT) for men with symptomatic BPH were eligible for this review. Comparison groups could include transurethral resection of the prostate, minimally invasive prostatectomy techniques, sham thermotherapy procedures, and medications. Outcome measures included urinary symptoms, urinary function, prostate volume, mortality, morbidity, and retreatment. Two reviewers independently identified potentially relevant abstracts and then assessed the full papers for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted study design, baseline characteristics and outcomes data and assessed methodological quality using a standard form. We attempted to obtain missing data from authors and/or sponsors. MAIN RESULTS: Fourteen studies involving 1493 patients met inclusion criteria, including six comparisons of microwave thermotherapy with TURP, seven comparisons with sham thermotherapy procedures, and one comparison with an alpha blocker. Study durations ranged from 3 to 60 months. The mean age of subjects was 66.8 years, and the baseline symptom scores and urinary flow rates, which did not differ across treatment groups, demonstrated moderately severe lower urinary tract symptoms. The pooled mean urinary symptom scores decreased by 65% with TUMT and by 77% with TURP. The weighted mean difference (WMD) (95% confidence interval) for the symptom score was -1.36 (-2.25 to -0.46), favoring TURP. The pooled mean peak urinary flow increased by 70% with TUMT and by 119% with TURP. The WMD for peak urinary flow was 5.08 (3.88 to 6.28) mL/s, favoring TURP. Compared to TURP, TUMT was associated with decreased risks for retrograde ejaculation, treatment for strictures, hematuria, blood transfusions, and the transurethral resection syndrome, but increased risks for dysuria, urinary retention, and retreatment for BPH symptoms. Microwave thermotherapy improved symptom scores (IPSS WMD -4.75, 95% CI -3.89 to -5.60) and peak urinary flow (WMD 1.67 mL/s, 95% CI 0.99 to 2.34) compared with sham procedures. Microwave thermotherapy also improved symptom scores (IPSS WMD -4.20, 95% CI -3.15 to -5.25) and peak urinary flow (WMD 2.30 mL/s, 95% CI 1.47 to 3.13) in the one comparison with alpha blockers. No studies evaluated the effects of symptom duration, patient characteristics, prostate-specific antigen levels, or prostate volume on treatment response. AUTHORS' CONCLUSIONS: Microwave thermotherapy techniques are effective alternatives to TURP and alpha-blockers for treating symptomatic BPH for men with no history of urinary retention or previous prostate procedures and prostate volumes between 30 to 100 mL. However, TURP provided greater symptom score and urinary flow improvements and reduced the need for subsequent BPH treatments compared to TUMT. Small sample sizes and differences in study design limit comparison between devices with different designs and energy levels. The effects of symptom duration, patient characteristics, or prostate volume on treatment response are unknown.

Anticoagulant drugs increase natural killer cell activity in lung cancer.

BACKGROUND: In preclinical studies in animal models and in initial clinical trials, anticoagulation drugs have been shown to be effective in the prevention and treatment of haematogenous metastasis, and in the prolongation of survival in animal models. However, only a few studies have been performed on the direct influence of anticoagulation drugs on the immune system. OBJECTIVE: The purpose of this study is to determine the effect of warfarin, unfractioned heparin, low molecular weight heparins (LMWHs), and acetylsalicylic acid anticoagulants on the functional activity of natural killer (NK) cells. PATIENTS AND METHOD: Cytotoxic activity in patients with early, operable stages of non-small-cell lung cancer was compared with healthy volunteers. Cytotoxic studies were also carried out in tumor-bearing animals. RESULTS: Lung-cancer patients were characterized by significantly lower NK cell cytotoxicity (7.07 +/- 3.15) than healthy donors (44.12 +/- 10.62, P < 0.001). NK cell activation was found in both in vitro experiments using peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo in lung carcinoma patients after treatment with unfractionated heparin and fraxiparine. Similarly, potentiation of NK cell activity in Lewis lung carcinoma-bearing mice was found after therapy with unfractionated heparin. NK cell activity is lower in lung cancer patients than in normal subjects. CONCLUSIONS: NK cell activation was increased by LMWHs. Other anticoagulants augment the effector function of NK cells in cancer patients and in an animal model of lung cancer. This is a novel effect of these compounds, which were thought previously to exert their effect only via their anticoagulant properties.

Monitoring of skeletal progression of prostate cancer by GFP imaging, X-ray, and serum OPG and PTHrP.

BACKGROUND: Prostate cancers (PCas) produce factors that can serve as biomarkers for tumor metastasis and bone progression. Transduced GFP expression by cancer cells can be imaged to monitor therapy. We exploited both concepts by developing a GFP-expressing PCa cell line that expresses PTHrP and studying it in an animal model of malignancy with methods that assess the skeletal progression of this tumor. METHODS: We developed a GFP-producing PCa cell line by stable transduction of PC-3 PCa cells. This PC-3 variant was used to study tumor progression in an immunocompromised mouse model. Skeletal progression of the PCa cells and the effects of pamidronate administration were evaluated radiologically, fluorometrically, and by measurement of serum tumor markers. RESULTS: The PC-3 cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3 cells could be monitored by GFP optical imaging, X-ray, and by measurements of tumor products in serum, notably PTHrP and OPG. Pamidronate treatment reduced tumor burden as assessed at autopsy by imaging and biomarkers. CONCLUSIONS: Pamidronate treatment exhibited anti-tumor effects that were reflected by decreases in serum PTHrP, OPG, and by GFP and radiological imaging procedures. Imaging of GFP expression enables real-time monitoring of tumor growth in the bone. PTHrP and OPG may be useful as tumor biomarkers for PCa that has metastasized to bone. This novel human PCa model can be used to study the clinical potential of diagnostic and therapeutic modalities in the skeletal progression of PCas.

Weight prediction from linear measures of growing Thoroughbreds.

REASON FOR PERFORMING STUDY: Monitoring weight of foals is a useful management practice to aid in maximising athletic potential while minimising risks associated with deviations from normal growth. OBJECTIVE: To develop predictive equations for weight, based on linear measurements of growing Thoroughbreds (TBs). METHODS: Morphometric equations predicting weight from measurements of the trunk and legs were developed from data of 153 foals. The accuracy, precision and bias of the best fitting equation were compared to published equations using a naive data set of 22 foals. RESULTS: Accuracy and precision were maximised with a broken line relating calculated volumes (V(t + l)) to measured weights. Use of the broken line is a 2 step process. V(t + l) is calculated from linear measures (m) of girth (G), carpus circumference (C), and length of body (B) and left forelimb (F). V(t + I) = ([G2 x B] + 4[C2 x F]) 4pi. If V(t + l) < 0.27 m3, weight is estimated: Weight (kg) = V(t + l) x 1093. If V(t + l) > or = 0.27 m3: Weight (kg) = V(t + l) x 984 + 24. The broken line was more accurate and precise than 3 published equations predicting the weight of young TBs. CONCLUSIONS: Estimation of weight using morphometric equations requires attention to temporal changes in body shape and density; hence, a broken line is needed. Including calculated leg volume in the broken line model is another contributing factor to improvement in predictive capability. POTENTIAL RELEVANCE: The broken line maximises its value to equine professionals through its accuracy, precision and convenience.

Laser prostatectomy for benign prostatic obstruction.

BACKGROUND: Symptomatic benign prostatic obstruction is a common problem for older men. The gold standard treatment, transurethral resection of the prostate (TURP), significantly improves urinary symptoms and urinary flow. However, TURP has up to a 20% morbidity. Currently, there are a number of minimally invasive procedures that may be safe, effective alternatives to TURP. One promising surgical technique is laser prostatectomy. OBJECTIVES: To assess the therapeutic efficacy and safety of laser prostatectomy techniques for treating men with symptomatic benign prostatic obstruction. SEARCH STRATEGY: Randomized controlled trials were identified from the Cochrane Collaboration Library, MEDLINE, EMBASE, bibliographies of retrieved articles and reviews, and contacting expert relevant trialists and laser manufacturers. SELECTION CRITERIA: All randomized controlled trials evaluating laser prostatectomy treatment for men with symptomatic BPH. Trials were eligible if they (1) were randomized comparisons of a laser technique with TURP, (2) included at least 10 men with BPO in each treatment arm, (3) provided at least 6-months follow-up, and (4) included clinical outcomes such as urologic symptom scales or urodynamic measurements. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodologic quality was performed independently by two reviewers. Information on study design, subject and treatment characteristics, adverse events, urinary symptoms, and urinary flow were extracted using a standard form. MAIN RESULTS: 20 studies involving 1898 subjects were evaluated, including studies 4 with multiple comparisons. We found 8 comparisons of TURP with contact lasers, 8 with non-contact lasers, 4 with hybrid techniques, and one with interstitial laser coagulation (ILC). Two studies compared transurethral electrovaporization (TUVP) with contact lasers, one study compared interstitial laser coagulation with transurethral microwave thermotherapy (TUMT), and one study compared holmium contact lasers (HoLRP) with open prostatectomy. Among the studies comparing laser prostatectomy with TURP, follow-up duration ranged from 6 to 36 months. Mean age (67.2 yrs), mean baseline symptom score (20.2), and mean baseline peak urinary flow (9.2 ml/s) did not differ by treatment group. The pooled percentage improvements for mean urinary symptoms ranged from 59% to 68% with lasers and 63% to 77% with TURP. The improvements for mean peak urinary flow ranged from 56% to 119% with lasers and 96% to 127% with TURP. Overall, laser subjects were less likely to receive transfusions or develop strictures and their hospitalizations were shorter. Non-contact laser subjects were more likely to have dysuria, urinary tract infection, and retention. Re-operation occurred more often following laser procedures. REVIEWER'S CONCLUSIONS: Laser techniques are a useful alternative to TURP for treating BPO. Small sample sizes and differences in study design limit any definitive conclusions regarding the preferred type of laser technique. Data were insufficient to compare laser techniques with other minimally invasive procedures.

Antioxidant supplementation and subsequent oxidative stress of horses during an 80-km endurance race.

This study tested the development of oxidative stress and the effects of antioxidant supplementation in an 80-km ride. A precompetition survey revealed that no competitor would participate without vitamin E supplementation; therefore, 46 horses were paired for past performances and randomly assigned to two groups of 23 each for 3 wk of supplementation before the ride. One group (E) was orally supplemented with 5,000 IU of vitamin E per day; the other group (E+C) received that dose of vitamin E plus 7 g/d of vitamin C. Blood samples, temperature, and heart rate were taken the day before the race, at 21 and 56 km during the ride, at completion, and after 20 min of recovery. Plasma was assayed for lipid hydroperoxides, alpha-tocopherol, total ascorbate, albumin, creatine kinase (CK), and aspartate aminotransferase (AST). Total glutathione and glutathione peroxidase activity were determined in red blood cells and white blood cells. Thirty-four horses completed the race, 12 horses (six in E and six in E+C) did not finish for reasons including lameness, metabolic problems, and rider option. Plasma ascorbate was higher (P = 0.045) in the E+C group than in the E group. Other than ascorbate, neither antioxidant status nor CK and AST activities were affected by supplementation with E+C vs. E. Red blood cell glutathione peroxidase, white blood cell total glutathione, lipid hydroperoxides, CK, and AST increased, and red blood cell total glutathione and white blood cell glutathione peroxidase activity decreased with distance (P < 0.001). Positive correlations were found for plasma lipid hydroperoxides on CK (r = 0.25; P = 0.001) and AST (r = 0.33; P < 0.001). These results establish an association between muscle leakage and a cumulative index of oxidative stress.