The strictured segment of small bowel including the perforation w

The strictured segment of small bowel including the perforation was resected. HIF inhibitor A salpingo–oophorectomy and an

appendicectomy were done. A manual end-to-end ileal anastomosis was fashioned and the abdominal cavity thoroughly lavaged with copious amount of saline. No drain was inserted because of the friable nature of the bowel and the localized nature of the peritonitis. Unfortunately, due to financial difficulties, microbiology of the purulent exudate was not requested and the excised specimen was not sent for histological examination. She received a therapeutic course of intravenous ceftriaxone 1 gm tds and metronidazole 500 mg tds for 7 days that covered the aerobes and anaerobes for a week. Apart for an ileus of 3 days, her recovery was uneventful. She was discharged on the 9th postoperative day on a 1 week course of doxycycline against Chlamydia trachomatis a frequent cause of pelvic inflammatory disease. Discussion During surgical abortion, perforation

of the uterus can occur or there may be damage to the cervix, which can predispose to the risk of preterm labour in subsequent pregnancies (cervical incompetence) [2]. There is also an increased risk of injury to infected tissue such as a tubo-ovarian abscess and spreading of the infection [3, 4]. In general, surgical procedures of the female genital tract place the patient at risk for pelvic inflammatory disease, with about 15% of pelvic infections occurring after procedures that break the cervical mucous barrier [8]. The incidence of upper genital https://www.selleckchem.com/products/ly2606368.html tract infection Cyclin-dependent kinase 3 associated with first-trimester abortion is about 1 in 200 cases and the incidence of complications after a first-trimester D&C is 1.7% [6]. Uterine perforation with small bowel involvement is rare in 1st trimester abortion. Shulman et al. [9] reported a case of uterine perforation and small bowel incarceration two days after a first trimester surgical abortion and correlated the sonographic and surgical findings. Without a preliminary

ultrasound scan it is uncertain in this case if the tubo-ovarian abscess was present at the time of the ‘D’ and ‘C’ or was a complication of the procedure. The clinical course of the combined complications of a tubo-ovarian abscess with small bowel obstruction and small bowel perforation can be explained in four possible patterns: (1) contaminated curettage instruments, (2) pre-existing tubo-ovarian abscess, (3) ‘sealed –off’ tubo-ovarian perforation and (4) unrecognized uterine injury with intra-abdominal involvement [9–12]. The evidence for (2) and (3) is that pelvic inflammatory disease may fix the uterus and moving it with dilators may tear it, spread the pus, and cause a fatal peritonitis [3]. The evidence for (4) is the presence of the ileal perforation within the abscess cavity and, the rarity of the reverse occurring – a tubo-ovarian abscess perforating into small bowel [5, 13].

A 1:1000 dilution of the 6 hour culture was made in LB broth and<

A 1:1000 dilution of the 6 hour culture was made in LB broth and

grown with agitation at 37°C overnight. A 1:200 dilution of the overnight culture was made in LB broth and divided into 16×100 glass tubes. Depending on the assay, the cultures were grown to either early-log (OD600 = 0.15) or late-log (OD600 = 0.6) with agitation before tetracycline addition. Growth curves Growth curves for H 89 each isolate were determined by diluting overnight cultures 1:200, growing to early-log phase (OD600 = 0.15), and adding serial dilutions of tetracycline (0–256 μg/ml); this corresponds to the early-log growth phase to be tested, and was necessary to determine the effect of the antibiotic at this time point. Cultures were shaken

continuously, and growth curve measurements (OD600) were taken every hour for 24 hours using a Bioscreen C instrument (Growth Curves LTD, Raisio, Finland). Differences between the no-antibiotic control and the other sample conditions during the logarithmic growth phase (0–9 hours) were determined by a one-way ANOVA with Dunnett’s post-test using GraphPad Prism 5 (GraphPad Software, Rucaparib San Diego, CA). P values less than 0.05 were considered significant. Experimental conditions The effect of tetracycline during early-log growth phase was examined using overnight cultures that were diluted 1:200 medroxyprogesterone in LB, subcultured into four tubes, and grown

to OD600 = 0.15. An aliquot was taken for RNA analysis from each culture and placed in RNAProtect (QIAGEN, Germantown, MD). Tetracycline was then added to a final concentration of 0 (control), 1, 4, and 16 μg/ml to the four tubes for each isolate, and these were incubated with agitation at 37°C for 30 min (final OD600 = ~0.30). Aliquots for RNA analysis were taken from each bacterial culture and placed in RNAProtect. An additional aliquot was taken from each culture for a cell culture invasion assay. To test the effect of tetracycline during late-log growth phase, each overnight culture was diluted 1:200 in LB, split into four tubes, and grown to OD600 = 0.15. An aliquot was taken for RNA analysis from each culture and placed in RNAProtect. After these cultures grew to OD600 = 0.

E coli was cultivated at 37°C and 200 rpm For growth of E coli

E. coli was cultivated at 37°C and 200 rpm. For growth of E. coli ST18 the media were supplemented with 50 μg/ml ALA. The results represent the mean value

of two independent experiments performed in duplicate. A standard deviation of up to 16% was observed. It was reported that several antibiotics, including tetracycline and gentamicin, can be affected in their www.selleckchem.com/products/Adriamycin.html chemistry by high salt concentrations as found in MB [27]. For example, the aminoglycoside kanamycin chelates Cu2+ [28] and tetracycline forms complexes with divalent cations such as Mg2+, Fe2+ and Ca2+. These interactions have no significant impact on the stability of tetracycline, but decrease the membrane permeability of a cell and therefore the bioavailability of this antibiotic [27, 29–31]. Up to ten times higher concentrations of gentamicin, carbenicillin, chloramphenicol and tetracycline were required for Roseobacter

growth inhibition in MB medium (data not shown) compared to hMB with lower sea salt concentrations (see below). Control experiments with E. coli showed that all used antibiotics were active over the whole incubation time in hMB at chosen conditions (data not shown). Consequently, hMB medium was used for further investigations. Screening of Roseobacter clade PI3K Inhibitor Library bacteria for antibiotic susceptibility The six different species of the Roseobacter clade were examined for Sclareol their antibiotic susceptibility. Furthermore, seven strains of D. shibae, isolated from different marine sources, were tested for the degree of susceptibility difference within one species. Such strain-specific differences were

already described for other species as E. coli [32], Pseudomonas aeruginosa [33] and other pathogens [34]. Table 2 represents the MIC in hMB medium after 72 h at 30°C. We tested antibiotics from different chemical groups, which are commonly used in molecular biology, such as tetracycline, chloramphenicol, the aminoglycosides kanamycin, gentamicin, streptomycin and spectinomycin as well as the two β-lactam antibiotics ampicillin and carbenicillin. Concentrations of up to 500 μg/ml were used. Bacteria able to grow above a concentration of 100 μg/ml of the respective antibiotic were defined as resistant. Table 2 Susceptibility to antibiotics (Minimal inhibitory concentrations; MIC) of strains from the Roseobacter clade. Strain/Antibiotic Amp [μg/ml] Carb [μg/ml] Cm [μg/ml] Gm [μg/ml] Kan [μg/ml] Spec [μg/ml] Strep [μg/ml] Tc [μg/ml] Phaeobacter inhibens T5T 90 20 15 5 80 5 20 10 Phaeobacter gallaeciensis 2.

A similar pattern was observed in the current study in WT but not

A similar pattern was observed in the current study in WT but not MMP-9−/− mice, as the fecal microbiota of the latter group had no changes in diversity following infection. Colonization of the cecal mucosa by the murine pathogen Helicobacter hepaticus also reduces microbial diversity [38]. The distinct and stable fecal microbiome in MMP-9−/− mice identified in this study emphasizes Osimertinib chemical structure that the presence of MMP-9 in mouse colon supports a microbiome that

is more susceptible to C. rodentium colonization and reductions in microbial diversity. Given that MMP-9−/− (B6.FVB(Cg)-Mmp9 tm1Tvu /J) mice have a microbiota that is more resistant to C. rodentium colonization, this genotype should prove useful for future studies evaluating the contribution of microbe-microbe interactions to the pathogenesis of C. rodentium

infection and the maintenance of microbial diversity. The role of other MMPs in maintaining the fecal microbiota upon infectious challenge will also prove to be of interest in future experimental studies. Conclusions Microbe-microbe and host-microbe interactions are essential for maintaining gut health [1]. Although studies have shown that expression of matrix metalloproteinase 9 is associated with IBD, the influence of MMP-9 expression on gut microbial community dynamics has not been studied in vivo. This work demonstrates that, in a model of bacterial-induced colitis, the particular microbial community of MMP-9−/− mice Midostaurin ic50 contributes to reduced levels of C. rodentium preventing a reduction in the microbial diversity associated with infection [21]. An altered intestinal ecosystem may lead to changes in some of the protective, metabolic, structural and histological functions of the gut microbiome [39], which has driven scientists to develop unique microbial signatures that describe IBD [4].

Further analysis of the interaction between the microbiome and other MMPs upregulated in IBD [1–3, 8, 12] are required to yield further insight into microbe-microbe and host-microbe interactions. Methods Bacterial strains and growth conditions Resveratrol C. rodentium, strain DBS 100 (generously provided by the late Dr. David Schauer, Massachusetts Institute of Technology, Cambridge, MA) was grown on Luria-Bertani (LB) agar plates overnight at 37°C, followed by overnight culture in LB broth at 37°C without shaking, yielding a final bacterial concentration of approximately 109 colony-forming units (CFU)/mL. Mouse strains and bacterial infection Male and female wild-type (C57BL/6 J) and MMP-9−/− (B6.FVB(Cg)-Mmp9 tm1Tvu /J) mice aged 5–6 weeks were purchased (Jackson Laboratory, Bar Harbour, ME) and housed in the containment unit of Laboratory Animal Services at the Hospital for Sick Children in cages containing a maximum of 5 mice per cage. All mice were allowed free access to food and water (supplied from a controlled source) for the duration of the study protocol.

We believe it would drastically contribute to the improvement of

We believe it would drastically contribute to the improvement of current medical practice of renal diseases and ultimately provide great benefits to IgAN patients. Acknowledgments We thank Ms. Etsuko Shinozaki for technical assistance and Dr. Tetsu Kawano for revising the manuscript. Open AG-014699 datasheet Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. References 1. Koyama A, Igarashi M, Kobayashi M. Natural history and risk factors for immunoglobulin A nephropathy in Japan. Group on progressive renal diseases. Am

J Kidney Dis. 1997;4:526–32.CrossRef 2. Stratta P, Segoloni GP, Canavese C, Sandri L, Mazzucco G, Roccatello D, et al. Incidence of biopsy-proven primary glomerulonephritis in Italian province. Am J Kidney Dis. 1996;27:631–9.PubMedCrossRef 3. D’Amico G, Imbasciati selleck products E, Barbiano Di Belgioioso G, Bertoli S, Fogazzi G, Ferrario F, et al. Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients. Medicine (Baltimore). 1985;64:49–60. 4. Velo M, Lozano L, Egido J, Gutierrez-Millet V, Hernando L. Natural history of IgAN in patients followed up for more than ten years in Spain. Semin Nephrol. 1987;7:346–50.PubMed 5. Maschio G, Alberti D, Janin G, Locatelli F, Mann JFE, Motolese M, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril

on the progression of chronic renal insufficiency. N Engl J Med. 1996;334:939–45.PubMedCrossRef 6. Locatelli F. Antiproteinuric effect of losartan in patients with chronic renal disease. Nephrol Dial Transplant. 1997;12:2204–5.PubMedCrossRef 7. Wardle EN. Dipyridamole in the nephritides. Am J Ther. 1998;5:107–9.PubMedCrossRef 8. Schena P, Montenegro M, Scibittaro V.

Meta-analysis of randomized controlled trials in patients with primary IgA nephropathy. Nephrol Dial Transplant. 1990;1:47–52. 9. Bennet WM, Walker RG, Kinkid-Smith P. Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial. Clin Nephrol. 1989;31:128–31. 10. Hotta O, Taguma Y, Kurosawa K, Matsutani S. Early intensive therapy for clinical remission of active IgA nephropathy: a three-year follow-up study. Japan J Nephrol. 1993;35:81–7. 11. Hotta O, Sitaxentan Miyazaki M, Furuta T, Tomioka S, Chiba S, Horigome I, et al. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis. 2001;38:736–43.PubMedCrossRef 12. Sato M, Hotta O, Tomioka S, Horigome I, Chiba S, Miyazaki M, et al. Cohort study of advanced IgA nephropathy: efficacy and limitations of corticosteroids with tonsillectomy. Nephron Clin Pract. 2003;93:c137–45.PubMedCrossRef 13. Wong Y, Chen J, Wang Y, Chen Y, Wang L, Lv Y. A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy. Nephrol Dial Transplant.

(DOC 924 KB) Additional file 2 : Figure S2 Non-coverage rates at

(DOC 924 KB) Additional file 2 : Figure S2. Non-coverage rates at the phylum level. The figures show the non-coverage rates of different primers at the phylum level: A Primer 27F; B Primer 338F; C Primer 338R; D Primer 519F; E Protein Tyrosine Kinase inhibitor Primer 519R; F Primer 907R; G Primer 1390R; and H Primer 1492R. (DOC 214 KB) Additional file 3 : Table S1; Table S2; Table S3; Table S4; Table S5. Primer binding-site sequence variants. Frequently observed sequence

variants at different primer binding sites are listed in different tables: Table S1 Primer 27F; Table S2 Primer 338F; Table S3 Primer 338R; Table S4 Primer 519F; and Table S5 Primer 907R. (DOC 258 KB) Additional file 4 : Figure S3. Elimination of primer contamination. The figure shows the elimination of sequences that are thought to lack correct primer trimming in the Trichostatin A order RDP dataset. (DOC 463 KB) References 1. Olsen GJ, Lane DJ, Giovannoni SJ, Pace NR, Stahl DA: Microbial ecology and evolution: a ribosomal RNA approach. Annu Rev Microbiol 1986, 40:337–365.PubMedCrossRef 2. Schmidt TM, Delong EF, Pace NR: Analysis of a marine picoplankton community by 16S rRNA gene cloning and sequencing. J Bacteriol 1991, 173:4371–4378.PubMed 3. Sharkey FH, Banat IM, Marchant R: Detection and quantification of

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He received grant support

from GlaxoSmithKline, Merck Sha

He received grant support

from GlaxoSmithKline, Merck Sharpe & Dohme, Novartis, Roche, and the Flemish Fund for Scientific Research. He is a (alternate) member of a commission on drug reimbursement with the Belgian health authorities. J-Y Reginster has received consulting fees or payments for participating in advisory boards for Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, small molecule library screening and UCB. He has received lecture fees when speaking at the invitation of Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, and Novo Nordisk; and grant support from Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, and Servier. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Jones PJ, Asp NG, Silva P (2008) Evidence for health claims on foods: how much is

enough? Introduction and general remarks. J Nutr 138:1189S–1191SPubMed 2. Grossklaus R (2009) Codex recommendations on the scientific basis of health claims. Eur J Nutr 48(Suppl 1):S15–S22PubMedCrossRef 3. Asp NG, Bryngelsson NVP-BGJ398 cost S (2008) Health claims in Europe: new legislation and PASSCLAIM

for substantiation. J Nutr 138:1210S–1215SPubMed 4. Prentice A, Bonjour JP, Branca F, Cooper C, Flynn A, Garabedian M, Muller D, Pannemans D, Weber P (2003) PASSCLAIM—bone health and osteoporosis. Eur J Nutr 42(Suppl 1):I28–I49PubMed 5. Rizzoli R (2008) Nutrition: its role in bone health. Best Pract Res Clin Endocrinol Metab 22:813–829PubMedCrossRef 6. Vildagliptin Rizzoli R, Bianchi ML, Garabedian M, McKay HA, Moreno LA (2010) Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone 46:294–305PubMedCrossRef 7. Bonjour JP, Ammann P, Rizzoli R (1999) Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines. Osteoporos Int 9:379–393PubMedCrossRef 8. Muschler GF, Raut VP, Patterson TE, Wenke JC, Hollinger JO (2010) The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Tissue Eng Part B Rev 16:123–145PubMedCrossRef 9. Ammann P (2009) Bone strength and ultrastructure. Osteoporos Int 20:1081–1083PubMedCrossRef 10. Cashman KD (2002) Calcium intake, calcium bioavailability and bone health. Br J Nutr 87(Suppl 2):S169–S177PubMedCrossRef 11. Fairweather-Tait SJ, Teucher B (2002) Calcium bioavailability in relation to bone health.

Recent developments Sports Med 1999,27(2):73–80 PubMedCrossRef 4

Recent developments. Sports Med 1999,27(2):73–80.PubMedCrossRef 475. Lowery L, Berardi JM, Ziegenfuss AntioxidantsT: Sports Supplements. Edited by: Antonio J, Stout J. Baltimore, MD: Lippincott, Williams & Wilkins; 2001:260–78. 476. Gomez AL, Volek JS, Ratamess NA, Rubin MR, Wickham RB, Mazzetti https://www.selleckchem.com/products/Y-27632.html SA, Doan BK, Newton RU, Kraemer WJ: Creatine supplementation enhances body composition during short-term reisstance training overreaching. Journal of Strength and Conditioning

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(28 89 kg/m2 [95% CI 27 78 to 31 12]) p = 0 15, respectively The

controls was higher (81.10 kg [95% CI 72.08 to 84.70]) vs. (72.20 kg [95% CI 66.55 to 80.75]) p = 0.06, this was not significant. This discrepancy was attenuated when BMI was compared between the groups of cases and controls (30.50 kg/m2 [95% CI 28.50 to 32.69]) vs. (28.89 kg/m2 [95% CI 27.78 to 31.12]) p = 0.15, respectively. The metabolic variables were not statistically different in levels of

adiponectin, leptin, insulin, TNF alpha, total cholesterol, triglycerides, HDL, LDL, and levels of free fatty acids. There was only a significant difference in median fasting glucose, 74 mg/dl (95% CI 73 to 78.96) in the case group vs. 84 mg/dl (80.26 see more to 88.0) in the control group (p = 0.003); while the median HOMA was 2.2 (95% CI 1.6 to 3.0) vs. 2.9 (CI 95% 2.3 to 5.2) for cases PF-01367338 concentration and controls, respectively (p = 0.047). Table 1 Baseline and End of Study Anthropometric and Metabolic Measures in Controls and Cases   Baseline P+ End of the Study P+ A vs. 30.88) 28.80 (27.50 – 30.78) 0.74 0.76 0.0002* FM kg 26.7 (23.15 – 31.26) 32.6 (23.51 – 34.4) 0.08 27.60 (23.50 – 31.01) 29.40 (23.12 – 33.07) 0.67 0.58 0.0005* FFM kg 45.70 (42.13 – 48.26) 48.70 (46.20 – 50.29) 0.08 44.80 (41.75 – 47.94) 47.90 (45.80 – 49.39) 0.06 0.13 0.03* Waist cm 83 (80.38 – 88) 86.40 Tacrolimus (FK506) (82.02 – 91.98) 0.24 82.50 (79.76 – 86.15) 83 (79.50 – 86) 0.74 0.11 < 0.0001* Hip cm 108 (102.26 – 110.62) 112.5 (105.04 – 115.46) 0.07 106.5 (102.52 – 108.73) 108 (103 – 111) 0.76 0.54 0.0002* Waist to Hip Ratio 0.79 (0.76 - 0.81) 0.78 (0.77 - 0.81) 0.80

0.77 (0.75 – 0.80) 0.78 (0.75 – 0.79) 0.63 0.27 0.04* Adiponectin ug/ml 11.54 (7.88 – 15.26) 11.72 (7.29 – 15.06) 0.61 12.33 (8.36 – 15.60) 15.76 (9.96 – 23.44) 0.32 0.80 < 0.0001* Leptin ng/ml 30.33 (25.30 – 36.06) 28.31 (23.82 – 35.12) 0.71 29.42 (21.51 – 37) 18.13 (12.94 – 24.31) 0.002* 0.45 0.03* TNFa pg/ml 4.44 (4.10 – 6.14) 4.33 (2.90 – 5.31) 0.25 5.05 (4.12 – 6.76) 4.10 (3.53 – 4.98) 0.036* 0.12 0.93 Insulin, mg/dl 13.72 (11.47 – 24.95) 12.01 (8.64–16.74) 0.14 12.73 (10.70 – 19.43) 12.89 (6.42 – 14.37) 0.12 0.01* 0.17 Glucose, mg/dl 84 (80.26 – 88) 74 (73–78.96) 0.003* 86 (82.26 – 87) 82 (76.01 – 87) 0.39 0.80 0.05* CHOL, mg/dl 78 (59.05 – 149.02) 78 (62.03 – 111.79) 0.69 78 (65.79 – 113) 66 (59.03 – 99-95) 0.15 0.59 0.33 TGL mg/dl 160 (144.52 – 182.41) 153 (144.04 – 186.98) 0.87 165 (149.70 – 186.73) 168 (152.01 – 184.

g from cancer

cells under normoxic conditions that are c

g. from cancer

cells under normoxic conditions that are capable of producing abundant polyamines. We reported that cancer cells under hypoxia lose regulation of polyamine homeostasis and have increased polyamine uptake from surrounding tissues (Figure 2B, 1) [66]. The expression of the adhesion molecule CD44 is suppressed in response to hypoxia. Reduced CD44 expression is reported to promote cancer metastasis and invasion, allowing detachment of cancer cells from the primary tumor cluster and seems to contribute to the increased migration capacity of hypoxic HT-29 cells [67, 68]. In conjunction with hypoxia, increases in extracellular spermine specifically augmented hypoxia-induced decreases in CD44 expression, and these decreases correlated well with increased migration of cancer cells (HT-29) in a dose-dependent

manner [66]. In addition, several experiments www.selleckchem.com/products/epz-6438.html indicated a possible role for polyamines in the invasive potential of cancer cells [53, 55, 69]. Figure 2 Mechanism of cancer metastasis. A. Cancer cells produce proteases to destroy the surrounding matrix, and produce proteins to create new vessels. In cancer tissues, Tamoxifen there are areas where the oxygen supply is poor, which induces hypoxia. Hypoxic cancer cells lose their adhesion characteristics and have enhanced capacity for migration. B. (1) Polyamines synthesized by cancer cells are transferred to cancer cells under hypoxic conditions that have increased capacity for polyamine

uptake and decreased intracellular polyamine synthesis. The increase in polyamine concentration due to increased polyamine uptake decreases adhesion of cancer cells by decreasing adhesion molecule expression. (2) Polyamines are transferred to the blood cells. Increased polyamine uptake by immune cells results very in decreased production of tumoricidal cytokines and the amount of adhesion molecules, and these eventually attenuate the cytotoxic activities of immune cells. 5-b. Role of polyamines in cancer cell transmigration to the circulation Cancer invasion is the process in which cancer cells migrate through surrounding tissues and enter into a blood vessel, which enables cancer cells to be transported throughout the body and establish secondary tumors. Blood vessel entry requires that cancer cells not only have increased motility but also secrete enzymes that degrade the surrounding cells’ extracellular matrix (ECM), which is composed of the interstitial matrix and basement membrane, and provides structural support to cells. Cancer cells produce various proteinases, such as serine proteinase, matrix metalloproteinases (MMPs), cathepsins, and plasminogen activator that degrade the ECM [70–72]. In addition, cancer cells have the ability to create new blood vessels in the tumor, i.e. angiogenesis, so that cancer cells can obtain supplies of blood and oxygen [73].