Interleukin-1 receptor 1 deficiency worsens hepatocellular carcinoma, while gemcitabine treatment alleviates the hepatocellular carcinoma-induced increase in intra-hepatic immune cells.

BACKGROUND AND AIM: Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. METHODS: Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1ß levels in human and mouse serum were assessed. RESULTS: Interleukin-1ß levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1ß levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1ß concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. CONCLUSIONS: Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.

Direct effects of alcohol on gut-epithelial barrier: Unraveling the disruption of physical and chemical barrier of the gut-epithelial barrier that compromises the host-microbiota interface upon alcohol exposure.

The development of alcohol-associated diseases is multifactorial, mechanism of which involves metabolic alteration, dysregulated immune response, and a perturbed intestinal host-environment interface. Emerging evidence has pinpointed the critical role of the intestinal host-microbiota interaction in alcohol-induced injuries, suggesting its contribution to disease initiation and development. To maintain homeostasis in the gut, the intestinal mucosa serves as the first-line defense against exogenous factors in the gastrointestinal tract, including dietary contents and the commensal microbiota. The gut-epithelial barrier comprises a physical barrier lined with a single layer of intestinal epithelial cells and a chemical barrier with mucus trapping host regulatory factors and gut commensal bacteria. In this article, we review recent studies pertaining to the disrupted gut-epithelial barrier upon alcohol exposure and examine how alcohol and its metabolism can affect the regulatory ability of intestinal epithelium.

Experiences of Family Caregivers Providing Home Care to Older Patients With Cancer: A Qualitative Study.

BACKGROUND: Older patients with cancer receive anticancer therapy in outpatient settings, and care-related issues may occur after discharge, which often requires family caregivers (FCs) to play a significant role in providing cancer care at home. However, relatively few studies have been focused on exploring the care experiences of these FCs. PURPOSE: The aim of this study was to explore the care experiences of FCs caring for older family members with cancer at home. METHODS: A qualitative study design and in-depth individual interviews were used to explore the at-home care experiences of FCs of older patients with cancer. The research was conducted in chemotherapy outpatient settings of a medical center in northern Taiwan. Content analysis was used to analyze data. The analyses focused on first extracting meaningful units from the text and then inducting categories from these units and determining the major themes. RESULTS: Twenty FCs were interviewed. The three themes identified included (a) increased information needs and challenges in diet preparation and treatment decision making, (b) personal and patient-induced emotional stress, and (c) life rebalancing through the care experience. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings highlight the educational requirements, especially related to meeting personal dietary needs and obtaining psychological support, for FCs caring for older patients with cancer to help them rebalance their life.

[Nursing Care Experiences of Periwound Moisture-Associated Dermatitis After Simultaneous Pancreas-Kidney Transplantation].

Simultaneous pancreas-kidney (SPK) transplantation is the primary surgical treatment for type I diabetes mellitus with end-stage renal disease. However, this transplant surgery has a high-risk of surgical complications, including duodenal anastomotic leakage, which may lead to pancreas transplantation failure if the leakage worsens. This case report describes a patient who suffered from duodenal anastomotic leakage after SPK transplantation. The digestive enzymes eroded the wound and skin around the wound, resulting in periwound moisture-associated dermatitis. During the period of nursing care, the wound-care intervention was determined by interdisciplinary cooperation. In our case report, the periwound moisture-associated dermatitis healed completely under inter-hospital care. In clinical nursing practice, periwound moisture-associated dermatitis should be cared in combination with macerated wounds. We suggest the following: (1) control the moisture source; (2) use advanced dressings as the primary dressing with sterile gauze as a secondary dressing and silver antimicrobial dressings for infected wounds; (3) consider using negative pressure wound therapy for complicated chronic wounds; and (4) use a pH-neutral skin cleanser with non-woven gauze to clean the periwound skin and keep the skin clean and dry. Finally, we suggest isolating and protecting the skin with No Sting Barrier Film and a hydrocolloid dressing. We hope this nursing care experiences serves as a reference for the nursing care of periwound moisture-associated dermatitis resulting from duodenal anastomotic leakage during / after SPK transplantation.

Design of an Electronic Reminder System for Supporting the Integerity of Nursing Records.

The integrity of electronic nursing records (ENRs) stands for the quality of medical records. But patients' conditions are varied (e.g. not every patient had wound or need fall prevention), to achieve the integrity of ENRs depends much on clinical nurses' attention. Our study site, an one 2,300-bed hospital in northern Taiwan, there are a total of 20 ENRs including nursing assessments, nursing care plan, discharge planning etc. implemented in the whole hospital before 2014. It become important to help clinical nurses to decrease their human recall burden to complete these records. Thus, the purpose of this study was to design an ENRs reminder system (NRS) to facilitate nursing recording process. The research team consisted of an ENR engineer, a clinical head nurse and a nursing informatics specialist began to investigate NRS through three phases (e.g. information requirements; design and implementation). In early 2014, a qualitative research method was used to identify NRS information requirements through both groups (e.g. clinical nurses and their head nurses) focus interviews. According to the their requirements, one prototype was created by the nursing informatics specialist. Then the engineer used Microsoft Visual Studio 2012, C#, and Oracle to designed a web-based NRS (Figure 1). Then the integrity reminder system which including a total of twelve electronic nursing records was designed and the preliminary accuracy validation of the system was 100%. NRS could be used to support nursing recording process and prepared for implementing in the following phase.

A magnetic vehicle realized tumor cell-targeted radiotherapy using low-dose radiation.

Radiotherapy, a common cancer treatment, often adversely affects the surrounding healthy tissue and/or cells. Some tumor tissue-focused radiation therapies have been developed to lower radiation-induced lesion formation; however, achieving tumor cell-targeted radiotherapy (i.e., precisely focusing the radiation efficacy to tumor cells) remains a challenge. In the present study, we developed a novel tumor cell-targeted radiotherapy, named targeted sensitization-enhanced radiotherapy (TSER), that exploits tumor-specific folic acid-conjugated carboxymethyl lauryl chitosan/superparamagnetic iron oxide (FA-CLC/SPIO) micelles to effectively deliver chlorin e6 (Ce6, a sonosensitizer) to mitochondria of HeLa cells under magnetic guidance. For the in vitro tests, the sensitization of Ce6 induced by ultrasound, that could weaken the radiation resistant ability of tumor cells, occurred only in Ce6-internalizing tumor cells. Therefore, low-dose X-ray irradiation, that was not harmful to normal cells, could exert high tumor cell-specific killing ability. The ratio of viable normal cells to tumor cells was increased considerably, from 7.8 (at 24h) to 97.1 (at 72h), after they had received TSER treatment. Our data suggest that TSER treatment significantly weakens tumor cells, resulting in decreased viability in vitro as well as decreased in vivo subcutaneous tumor growth in nude mice, while the adverse effects were minimal. Taken together, TSER treatment appears to be an effective, clinically feasible tumor cell-targeted radiotherapy that can solve the problems of traditional radiotherapy and photodynamic therapy.

Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial.

OBJECTIVE: To evaluate wound infection rates, pain scores, satisfaction with wound care, and wound care costs starting 48 hours after surgery. BACKGROUND: Showering after surgery is a controversial issue for wound care providers and patients. We investigated the benefits and detriments of showering for postoperative wound care. METHODS: Patients undergoing thyroid, lung, inguinal hernia, and face and extremity surgeries with clean or clean-contaminated wounds were included. The patients were randomized to allow showering (shower group) or to keep the wound dry (nonshower group) for postoperative wound care starting 48 hours after surgery. The primary endpoint was the rate of surgical wound infection. The secondary endpoints included the wound pain score, satisfaction with wound care, and cost of wound care. RESULTS: Between May 2013 and March 2014, there were 222 patients randomized to the shower group and 222 to the nonshower group. Two patients in each group were lost to follow-up. There were 4 superficial surgical site infections in the shower group and 6 in the nonshower group (4/220, 1.8% vs 6/220, 2.7%, P = 0.751). Postoperative pain scores were comparable between the 2 groups. Patients in the shower group were more satisfied with their method of wound care, and their wound care costs were lower when compared with the nonshower group. CONCLUSIONS: Clean and clean-contaminated wounds can be safely showered 48 hours after surgery. Postoperative showering does not increase the risk of surgical site complications. It may increase patients' satisfaction and lower the cost of wound care.

A novel micelle-forming material used for preparing a theranostic vehicle exhibiting enhanced in vivo therapeutic efficacy.

A new micelle-forming material, folic acid-conjugated carboxymethyl lauryl chitosan (FA-CLC), and superparamagnetic iron oxide (SPIO) nanoparticles were used for preparing an imaging-guided drug vehicle (the FA-CLC/SPIO hybrid micelle) that demonstrates targeted delivery, imaging, and controlled release of hydrophobic agents. We found that the ratio of viable normal cells to tumor cells was increased prominently after delivery of camptothecin (CPT)-loaded FA-CLC/SPIO micelles and therapeutic sonication. In addition, a magnetic field could enhance the tumor-targeting effect of FA-CLC/SPIO micelles. Therefore, after sequential administration of magnetic attraction to CPT-loaded FA-CLC/SPIO micelles, and therapeutic sonication, the in vivo therapeutic efficacy of CPT was markedly enhanced. However, a nonfocused magnetic field could enhance the undesirable accumulation of iron-containing vehicles in the liver if the tumor (i.e., magnetic attraction site) is near the liver. We propose that magnetic attraction must be carefully applied, far from the liver.

Using second-derivative filters to assist in width estimations of size exclusion chromatography signal peaks with static light-scattering detections to obtain more accurate molecular weight.

Static light-scattering (LS) detection can determine the molecular weight (MW) of polymers eluted with size-exclusion chromatography (SEC) without using any standards when the differential refraction index (RI) of solutes are obtained. On the other hand, the noisy chromatographic signal peak acquired using a static LS detector often causes difficulty in peak-width recognition. This disadvantage limits the determination accuracy and precision of the MW values. This study developed one second-order derivative filtering procedure by convolving the original LS chromatogram against the second-derivative curve of one artificial Gaussian-shape chromatographic peak to suppress the noises and to correct the baseline of the chromatogram. More accurate estimations of the chromatographic peak widths of pullulan samples were achieved to improve the MW determination accuracy. For noisy original chromatography peaks of pullulan 5 k (SNR of approximately 10), the non-ideal determination accuracy of the MW values (9.3%) is improved to -1.3% with the assistance of the filtering procedures.

A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality.

In the present study, a new bubble-forming material (carboxymethyl hexanoyl chitosan, CHC), together with superparamagnetic iron oxide (SPIO) nanoparticles, was employed to prepare image-guided bubbles for efficiently encapsulating and delivering hydrophobic agents to kill tumor cells. The results showed that CHC could be used for preparing not only micronized bubbles (CHC/SPIO MBs) to exhibit ultrasound imaging functionality but also nanosized bubbles (CHC/SPIO NBs) to exhibit magnetic resonance T2 image contrast. It was found that the amounts of SPIO nanoparticles and hexane during preparation process were the key factors to obtaining CHC/SPIO NBs. Most importantly, under in vitro cell culture conditions with the same amount of camptothecin (CPT) and therapeutic sonication, CPT-loaded CHC/SPIO NBs demonstrated more significant transcellular delivery and cytotoxicity than free CPT. Subsequently, an intratumoral injection was proposed for the in vivo administration of hydrophobic-agent-loaded CHC/SPIO NBs. After injection, the distribution of a hydrophobic dye (DiR, an agent with near-infrared (NIR) fluorescence used as a model drug) released from the CHC/SPIO NBs was tracked by an NIR imaging technique. A significant tumor-specific accumulation was observed in the mouse that received the DiR-loaded CHC/SPIO NBs; the same was not observed in the mouse that received the free dye (without incorporating with CHC/SPIO NBs). It is expected, in the future, both the dose of the therapeutic agent administered and its side effects can be significantly lowered by using novel CHC/SPIO NBs together with local delivery (intratumoral injection), targeted imaging and enhanced cellular uptake of the drug.

Using induced electroosmotic micromixer to enhance the reproducibility of chemiluminescence intensity.

In this study, induced electroosmotic vortex flows were generated using an AC electric field by one pair of external electrodes to rapidly mix luminescence reagents in a 30 µL micromixer and enhance the reproducibility of chemiluminescence (CL) assays. A solution containing the catalyst reagent ferricyanide ions (4 µL) was pipetted into a reservoir containing luminol to produce CL in the presence of hydrogen peroxide. When the added ferricyanide aliquot contacted the reservoir solution, the CL began flashing, but rapidly diminished as the ferricyanide was consumed. In such a short illumination period, the solutes could not mix homogeneously. Therefore, the reproducibility of CL intensities collected using a CCD and multiple aliquot additions was determined to be inadequate. By contrast, when the solutes were efficiently mixed after adding a ferricyanide aliquot to a micromixer, the intensity reproducibility was significantly improved. When the CL temporal profile was analyzed using a PMT, a consistent improvement in reproducibility was observed between the CL intensity and estimated CL reaction rate. Replicating the proposed device would create a multiple well plate that contains a micromixer in each reservoir; this system is compatible with conventional CL instrumentation and requires no CL enhancer to slow a reaction.

Osteopontin promoter polymorphisms are associated with susceptibility to gastric cancer.

GOALS: To evaluate the significance of osteopontin (OPN) genotypes in the susceptibility to gastric cancer. BACKGROUND: The expression of OPN has been correlated with development, invasiveness, metastasis, and survival of gastric cancer, but the role of polymorphisms in the OPN promoter has not been investigated. STUDY: We enrolled 146 gastric cancer patients and 128 controls. DNA was extracted from peripheral blood leucocytes. Single-nucleotide polymorphisms (SNPs) in the OPN promoter (-66, -156, -443, -616, -1748, and -1776) were analyzed by pyrosequencing and direct sequencing methods. Logistic regression analyses were used to evaluate the associations between SNPs and development of gastric cancer. RESULTS: SNP -443 C/C and -616 T/T of the OPN promoter were significantly associated with gastric cancer [odds ratio (OR)=2.88; 95% confidence interval (CI), 1.16-7.12 and OR=1.95; 95% CI, 1.35-2.82, respectively]. Analysis of the combined effect of OPN promoter SNPs revealed that the combination of SNP -443 (T/C or C/C) and SNP -616 (T/T or T/G) had the most significant association with gastric cancer (OR=3.95; 95% CI, 1.58-9.90). CONCLUSIONS: Our results suggest that polymorphisms in the OPN promoter are associated with the development of gastric cancer, and the combination of SNP -443 (T/C or C/C) and -616 (T/T or T/G) most significantly increases susceptibility to gastric cancer.

MMP-9 -1562 Promoter Polymorphism Associated with Gastric Cancer Risk in Females.

Background/Aims: C to T transition at the matrix metalloproteinase-9 (MMP-9) promoter site -1562 abolishes a binding site of a putative transcription repressor protein to the C allelic promoter. The aim of this study is to elucidate the significance of MMP-9 genotypes in clinicopathological manifestations of gastric cancer. Methodology: We conducted a case-control study based on previously stored peripheral blood samples from 263 gastric cancer patients and 354 controls. MMP-9 genotyping was analyzed by PCR-RFLP method. Stratified analysis, logistic regression and Cox proportional hazards analysis were used to evaluate the associations between polymorphisms and gastric cancer development, invasiveness, and survival. Results: There was significant correlation between female patients with MMP-9 -1562 C/T or T/T genotype and higher risk of gastric cancer (OR=2.12, p=0.02). On stratified analysis, only elderly females with T allele had higher risk of gastric cancer (OR=2.64, p=0.04). On Cox proportional hazards analysis, serosal invasion (adjusted HR=3.47, p<0.001) and lymph node metastasis (adjusted HR=2.31, p=0.003), but not MMP-9 polymorphism, were independent prognostic factors for survival. Conclusions: MMP-9 -1562 promoter polymorphism with T allele may be used as a marker to predict gastric cancer development in female subjects, especially in the elderly.

Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies.

OBJECTIVE: Type 2 diabetes mellitus is associated with a higher risk of hepatocellular carcinoma (HCC), which is attenuated by the use of metformin. However, there are no studies addressing the effect of metformin on hepatocarcinoma cells from the antitumoural perspective. DESIGN: In the nationwide case-control study, the authors recruited 97,430 HCC patients and 19,860 age-, gender- and physician visit date-matched controls. The chemopreventive effects of metformin were examined by multivariate analysis and stratified analysis. The in vitro effects of metformin on cell proliferation and cell cycle were studied in HepG2 and Hep3B hepatoma cell lines. RESULTS: The OR of diabetes in HCC patients was 2.29 (95% CI 2.25 to 2.35, p<0.001). Each incremental year increase in metformin use resulted in 7% reduction in the risk of HCC in diabetic patients (adjusted OR=0.93, 95% CI 0.91 to 0.94, p<0.0001). In the multivariate stratified analysis, metformin use was associated with a reduced risk of HCC in diabetic patients in nearly all subgroups. Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53. Combined treatment of oral metformin with doxorubicin functioned more efficiently than either agent alone, in vivo. CONCLUSIONS: Use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner, via inhibition of hepatoma cells proliferation and induction of cell cycle arrest at G0/G1 phase.

Selective dynamic concentration of peptides at poles of cation-selective nanoporous granules.

The authors exposed a non-equilibrium dynamic counterion and coion analyte concentration to an AC electric field to selectively concentrate peptides at the poles of a cation-selective granule. The counterion polarization results from the focusing of the electric field show a discontinuous drop in the intra-granule counterion electromigration flux at the pole. The coion concentration polarization is due to the combined external convective and electromigration fluxes toward the pole that neutralize the accumulating counterions. Because the electromigration mobility of the peptide anion analyte depends on the pH, the authors determined a 20 000-fold high concentration factor for a near-neutral pH of 6.0 to 7.7. Because the peptide is protonated at the acidic pole and its absolute charge ranges from -0.3 to -1.9, the concentration factor scales exponentially with the absolute charge, thus allowing extremely selective concentrations of various peptides, which is demonstrated by fluorescein isothiocyanate tagged angiotensin I (pI ∼ 5.8) and Texas red tagged avidin (pI ∼ 10.5). This dynamic concentration effect can substantially enhance the sensitivity of bio-assays.

Improving liquid chromatography-tandem mass spectrometry determinations by modifying noise frequency spectrum between two consecutive wavelet-based low-pass filtering procedures.

This paper employs one chemometric technique to modify the noise spectrum of liquid chromatography-tandem mass spectrometry (LC-MS/MS) chromatogram between two consecutive wavelet-based low-pass filter procedures to improve the peak signal-to-noise (S/N) ratio enhancement. Although similar techniques of using other sets of low-pass procedures such as matched filters have been published, the procedures developed in this work are able to avoid peak broadening disadvantages inherent in matched filters. In addition, unlike Fourier transform-based low-pass filters, wavelet-based filters efficiently reject noises in the chromatograms directly in the time domain without distorting the original signals. In this work, the low-pass filtering procedures sequentially convolve the original chromatograms against each set of low pass filters to result in approximation coefficients, representing the low-frequency wavelets, of the first five resolution levels. The tedious trials of setting threshold values to properly shrink each wavelet are therefore no longer required. This noise modification technique is to multiply one wavelet-based low-pass filtered LC-MS/MS chromatogram with another artificial chromatogram added with thermal noises prior to the other wavelet-based low-pass filter. Because low-pass filter cannot eliminate frequency components below its cut-off frequency, more efficient peak S/N ratio improvement cannot be accomplished using consecutive low-pass filter procedures to process LC-MS/MS chromatograms. In contrast, when the low-pass filtered LC-MS/MS chromatogram is conditioned with the multiplication alteration prior to the other low-pass filter, much better ratio improvement is achieved. The noise frequency spectrum of low-pass filtered chromatogram, which originally contains frequency components below the filter cut-off frequency, is altered to span a broader range with multiplication operation. When the frequency range of this modified noise spectrum shifts toward the high frequency regimes, the other low-pass filter is able to provide better filtering efficiency to obtain higher peak S/N ratios. Real LC-MS/MS chromatograms, of which typically less than 6-fold peak S/N ratio improvement achieved with two consecutive wavelet-based low-pass filters remains the same S/N ratio improvement using one-step wavelet-based low-pass filter, are improved to accomplish much better ratio enhancement 25-folds to 40-folds typically when the noise frequency spectrum is modified between two low-pass filters. The linear standard curves using the filtered LC-MS/MS signals are validated. The filtered LC-MS/MS signals are also reproducible. The more accurate determinations of very low concentration samples (S/N ratio about 7-9) are obtained using the filtered signals than the determinations using the original signals.

Clinicopathological significance of urokinase-type plasminogen activator genotypes in gastric cancer.

BACKGROUND/AIMS: The roles of urokinase-type plasminogen activator (uPA) expression in tumor occurrence, invasion and prognosis have been established. However, how uPA genetic polymorphisms influence the occurrence and outcome of tumors is not as clear. METHODOLOGY: We conducted a case-control study based on previously stored peripheral blood samples from 237 gastric cancer patients and 242 healthy controls. uPA exon 6 and intron 7 genotypes were determined by direct DNA sequencing. Logistic regression analyses and Cox proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features, and survival. RESULTS: uPA exon 6 C/T and intron 7 T/C polymorphisms did not correlate well with gastric cancer susceptibility. uPA exon 6 T/C and T/T genotypes were associated with venous invasion and lymphatic invasion, but not with stage, serosal invasion or lymph node metastasis. uPA intron 7 T/C polymorphism did not correlate well with invasive phenotype of gastric cancer. On Cox proportional hazards analyses, uPA exon 6 and intron 7 polymorphisms were not independent prognostic factors for survival. CONCLUSIONS: uPA exon 6 C/T polymorphism is associated with invasive phenotype of gastric cancer, but not with susceptibility or survival of gastric cancer. uPA intron 7 is a silent polymorphism.

Dynamic superconcentration at critical-point double-layer gates of conducting nanoporous granules due to asymmetric tangential fluxes.

A transient 10(6)-fold concentration of double-layer counterions by a high-intensity electric field is demonstrated at the exit pole of a millimeter-sized conducting nanoporous granule that permits ion permeation. The phenomenon is attributed to a unique counterion screening dynamics that transforms half of the surface field into a converging one toward the ejecting pole. The resulting surface conduction flux then funnels a large upstream electro-osmotic convective counterion flux into the injecting hemisphere toward the zero-dimensional gate of the ejecting hemisphere to produce the superconcentration. As the concentrated counterion is ejected into the electroneutral bulk electrolyte, it attracts co-ions and produce a corresponding concentration of the co-ions. This mechanism is also shown to trap and concentrate co-ion microcolloids of micron sizes too (macroions) and hence has potential application in bead-based molecular assays.

Clinicopathological significance of MMP-2 and TIMP-2 genotypes in gastric cancer.

AIMS: Single nucleotide polymorphisms in matrix metalloproteinase-2 (MMP-2) -1306 C/T and tissue inhibitor of metalloproteinase-2 (TIMP-2) -418 G/C abolish the Sp-1 binding site and down-regulate expression of these genes. We aim to elucidate the role of MMP-2 and TIMP-2 in clinicopathological manifestations of gastric cancer. METHODS: We enrolled 240 gastric cancer patients and 283 controls. DNA was extracted from peripheral blood leucocytes. MMP-2 and TIMP-2 genotypes were analysed by PCR-direct sequencing and PCR-RFLP method, respectively. RESULTS: MMP-2 and TIMP-2 genotypes were not associated with gastric cancer development. However, patients with MMP-2 -1306 C/C genotype showed higher risk of lymphatic invasion (odds ratio (OR)=2.77, p=0.01) and venous invasion (OR=2.93, p=0.012). TIMP-2 G/G genotype was associated with serosal invasion (OR=1.89, p=0.009), lymph node metastasis (OR=2.19, p=0.021), lymphatic invasion (OR=2.87, p=0.016) and venous invasion (OR=2.65, p=0.033). CONCLUSION: Our results suggest MMP-2 and TIMP-2 genotypes play a crucial role in gastric cancer invasion, but not with development of gastric cancer.