Complicated urinary tract infections (cUTIs) are difficult to treat, consume substantial resources, and cause increased patient morbidity. Data suggest that cUTI may be caused by polymicrobial and ...fastidious organisms (PMOs and FOs, respectively); as such, urine culture (UC) may be an unreliable diagnostic tool for detecting cUTIs. We sought to determine the utility of PCR testing for patients presumed to have a cUTI and determine the impact of PCR panel size on organism detection. We reviewed 36,586 specimens from patients with presumptive cUTIs who received both UC and PCR testing. Overall positivity rate for PCR and UC was 52.3% and 33.9%, respectively (p < 0.01). PCR detected more PMO and FO than UC (PMO: 46.2% vs. 3.6%; FO: 31.3% vs. 0.7%, respectively, both p < 0.01). Line-item concordance showed that PCR detected 90.2% of organisms identified by UC whereas UC discovered 31.9% of organisms detected by PCR (p < 0.01). Organism detection increased with expansion in PCR panel size from 5–25 organisms (p < 0.01). Our data show that overall positivity rate and the detection of individual organisms, PMO and FO are significantly with PCR testing and that these advantages are ideally realized with a PCR panel size of 25 or greater.
Dermatofibrosarcoma protuberans (DFSP) is a slow growing, low- to intermediate-grade dermal soft-tissue tumor. It has a high local recurrence rate but low metastatic potential. It is characterized by ...a uniform spindle cell arrangement, classically with a storiform pattern and CD34 immunoreactivity. The histomorphology and immunophenotype overlap with a broad range of other neoplasms. The standard treatment is complete surgical excision. The surgical procedures include wide local excision (WLE) with tumor free margins, Mohs micrographic surgery (MMS) and amputation. Unresectable DFSPs are treated with radiation therapy and/or targeted therapy. DFSP has characteristic t(17; 22) (q22; q13), resulting in a COL1A1- PDGFB fusion transcripts in more than 90% of DFSPs. Molecular detection of the gene rearrangement or fusion transcripts is helpful for the diagnosis of patients with atypical morphology and for screening candidates for targeted therapy with tyrosine kinase inhibitors. The aims of the present review are to update the clinical presentation, tumorigenesis and histopathology of DFSP and its variants for diagnosis and differential diagnosis from other benign and malignant tumors, to compare the advantages and drawbacks of WLE and MMS, to propose the baseline for selecting surgical procedure based on tumor’s location, size, stage and relationship with surrounding soft tissue and bone structures, and to provide a biologic rationale for the systemic therapy. We further propose a modified clinical staging system of DFSP and a surveillance program for the patients after surgical excision.
In studying the cancer-preventive activities of green tea polyphenols, we previously demonstrated that dietary administration of polyphenon E (PPE) inhibited the formation of aberrant crypt foci ...(ACF) in the colon of azoxymethane (AOM)-treated F344 rats. Herein, we reported cancer-preventive activity of PPE using colorectal cancer as an end point. F344 rats were given two weekly injections of AOM, and then maintained on a 20% high-fat diet with or without 0.24% PPE for 34 wk. In the control group, 83% of rats developed colorectal tumors. Dietary PPE treatment significantly increased the plasma and colonic levels of tea polyphenols, and decreased tumor multiplicity and tumor size. Histological analysis indicated that PPE significantly decreased the incidence of adenocarcinoma, and the multiplicity of adenocarcinoma as well as the multiplicity of adenoma. PPE treatment significantly decreased plasma levels of proinflammatory eicosanoids, prostaglandin E2, and leukotriene B4. It also decreased β-catenin nuclear expression, induced apoptosis, and increased expression levels of RXRα, β, and γ in adenocarcinomas. In conclusion, our results convincingly demonstrated the inhibitory effects of orally administered PPE on colon carcinogenesis in AOM-treated rats and suggested possible biomarkers for the biological effects of green tea polyphenols.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Mycetoma describes a heterogeneous group of cutaneous and subcutaneous infections caused by either fungi (eumycetomas) or bacteria (actinomycetomas). It is characterized by a triad of clinical ...symptoms: painless subcutaneous tumor-like swelling, multiple sinuses and fistulas, and discharged grains in pus. This predominantly affects the feet in more than 70% of patients. It is endemic in the “mycetoma belt” regions, including Africa, South America, and South Asia. Autochthonous mycetoma is rare in the United States of America (USA). We recently reported a Latin American immigrant with eumycetoma in the State of Maryland, USA. With millions of immigrants from endemic regions, the true number of mycetomas in the USA is most likely higher than currently recognized. With the aim to raise the awareness of clinicians about mycetoma, especially dermatologists and podiatrists, we update the development of the epidemiology, etiology, clinical presentations, pathogenesis, diagnosis, differential diagnosis, and treatment of mycetoma.
The present study investigated the inhibitory effects of Polyphenon E a standardized green tea polyphenol preparation containing 65% (-)-epigallocatechin-3-gallate and caffeine on ...4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation.
The nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a critical role in protecting various tissues against inflammation, which is a potential risk factor for colorectal and other cancers. Our ...previously published mouse model work showed that Nrf2 helps protect against dextran sulfate sodium (DSS)-induced colitis/inflammation, and others have shown that Nrf2 helps protect against inflammation-associated colorectal carcinogenesis (aberrant crypt foci). The present study extended these important earlier findings by exploring the role of Nrf2 in colitis-associated colorectal cancer in a mouse model involving azoxymethane/DSS-induced colorectal carcinogenesis in Nrf2 knockout mice. Azoxymethane/DSS-treated Nrf2 knockout mice had increased incidence, multiplicity, and size of all colorectal tumors, including adenomas, versus treated wild-type (WT) mice, and the proportion of tumors that were adenocarcinoma was much higher in knockout (80%) versus WT (29%) mice. Compared with WT mice, knockout mice also had increased markers of inflammation in tumor tissue (cyclooxygenase-2 and 5-lipoxygenase expressions and prostaglandin E(2) and leukotriene B(4) levels) and in inflamed colonic mucosa (nitrotyrosine expression), supporting the association of knockout mouse tumor formation with inflammation. The phase II detoxifying/antioxidant enzymes NAD(P)H-quinone reductase 1 and UDP-glucurosyltransferase 1A1 were elevated in the normal mucosa of WT, but not Nrf 2 knockout, mice treated with azoxymethane/DSS. Our findings show that Nrf2 plays a critical role in protecting against inflammation-associated colorectal cancer.
Purpose: Epidemiologic studies have linked the consumption of fruits and vegetables to reduced risk of several types of cancer. Laboratory
animal model studies have provided evidence that stilbenes, ...phenolic compounds present in grapes and blueberries, play a role
in inhibiting the risk of certain cancers. Pterostilbene, a naturally occurring stilbene from blueberries, was tested for
its preventive activity against colon carcinogenesis.
Experimental Design: Experiments were designed to study the inhibitory effect of pterostilbene against the formation of azoxymethane-induced colonic
aberrant crypt foci (ACF) preneoplastic lesions in male F344 rats. Beginning at 7 weeks of age, rats were treated with azoxymethane
(15 mg/kg body weight s.c., once weekly for 2 weeks). One day after the second azoxymethane treatment, rats were fed experimental
diets containing 0 or 40 ppm of pterostilbene. At 8 weeks after the second azoxymethane treatment, all rats were sacrificed,
and colons were evaluated for ACF formation and for inhibition of inducible nitric oxide synthase (iNOS) and proliferating
cell nuclear antigen. Effects on mucin MUC2 were also determined.
Results: Administration of pterostilbene for 8 weeks significantly suppressed azoxymethane-induced formation of ACF (57% inhibition,
P < 0.001) and multiple clusters of aberrant crypts (29% inhibition, P < 0.01). Importantly, dietary pterostilbene also suppressed azoxymethane-induced colonic cell proliferation and iNOS expression.
Inhibition of iNOS expression by pterostilbene was confirmed in cultured human colon cancer cells.
Conclusions: The results of the present study suggest that pterostilbene, a compound present in blueberries, is of great interest for
the prevention of colon cancer.
Green tea and its constituents have shown cancer-preventive activities in many animal models. In order to prepare for a human trial on the inhibition of colon carcinogenesis, we conducted a study ...with green tea polyphenols as the preventive agent in an azoxymethane (AOM)-induced rat colon cancer model using aberrant crypt foci (ACF) as an end point. F344 rats were given two weekly injections of AOM (15 mg/kg), and then fed a 20% high-fat diet with or without 0.12 or 0.24% Polyphenon E (PPE, a standardized green tea preparation consisting 65% of (−)-epigallocatechin-3-gallate and 22% of other catechins) for 8 weeks. Colorectal ACF were analyzed under a microscope after methylene blue staining. Dietary PPE administration was found to significantly and dose dependently decrease the total number of ACF per rat and the total number of aberrant crypt per rat. Moreover, treatment with 0.24% PPE also significantly decreased the percentage of large ACF (four or more crypts) and the percentage of ACF with high-grade dysplasia in total ACF. The high-grade dysplastic ACF from 0.24% PPE-treated group had increased apoptosis and decreased nuclear expression levels of β-catenin and cyclin D1. Retinoid X receptor (RXR)α expression was reduced in high-grade dysplastic ACF, adenoma and adenocarcinoma during AOM-induced colon carcinogenesis, and the PPE treatment partially prevented the loss of RXRα expression in high-grade dysplastic ACF. Taken together, our results strongly suggest the colon cancer-preventive activity of PPE and identified possible molecular markers for future colon cancer prevention studies.
Pak4 is a member of the B group of p21-activated (Pak) kinases, originally identified as an effector protein for Cdc42. Although
Pak4 is expressed at low levels in most adult tissues, it is highly ...overexpressed in tumor cell lines. Here, we show that
Pak4 is also overexpressed in primary tumors, including colon, esophageal, and mammary tumors. Overexpression of Pak4 also
leads to tumor formation in athymic mice, whereas deletion of Pak4 inhibits tumorigenesis. Although a constitutively active
Pak4 mutant was previously shown to promote oncogenic transformation in cultured cells, our results are the first to show
that Pak4 also promotes tumorigenesis in experimental animals. Furthermore, these results show for the first time that not
only constitutively active Pak4, but also wild-type Pak4, is transforming, when experimental animals are used. These results
are highly significant because wild-type Pak4, rather than activated Pak4, is overexpressed in tumor cells. Our results suggest
that overexpression or activation of Pak4 is a key step in oncogenic transformation, due to its ability to promote cell survival
and subsequent uncontrolled proliferation. The finding that Pak4 is up-regulated in so many types of cancers indicates that
Pak4 may play a vital role in a wide range of different types of cancer. This makes it an attractive candidate for drug therapy
for different types of cancer. (Mol Cancer Res 2008;6(7):1215–24)
ABSTRACT
Purpose
Prior studies from our laboratory have demonstrated the efficacy of a combined treatment of low doses of dietary agents curcumin and phenylethylisothiocyanate in effectively ...suppressing prostate cancer
in vitro
in human prostate cancer PC3 cells as well as
in vivo
in immunodeficient mice implanted with PC3 cells. Hence, this study was undertaken to examine the potential chemopreventive properties of the two agents against transgenic adenocarcinoma of the mouse prostate.
Materials and Methods
The efficacy of AIN-76A diet supplemented with 2% curcumin or 0.05% PEITC or a combination of 1% curcumin and 0.025% PEITC for periods of 10 and 16 weeks was tested against adenocarcinoma of the mouse prostate. Immunohistochemistry and Western blot analysis were used to examine the expression of proliferation and apoptotic biomarkers. All statistical tests were two-sided.
Results
Supplementing AIN-76A diet with dietary phytochemicals curcumin or PEITC either alone or in combination, significantly decreased incidence of prostate tumor formation (
P
= 0.0064). Immunohistochemistry revealed a significant inhibition of high-grade PIN (
P
= 0.0006, 0.000069, 0.00029 for a treatment period of 10 weeks and
P
= 0.02582, 0.022179, 0.0317 for a treatment period of 16 weeks) along with decreased proliferation and increased apoptotic index in the curcumin, PEITC or curcumin and PEITC treated animals, respectively. Furthermore, Western blot analysis revealed that downregulation of the Akt signaling pathway may in part play a role in decreasing cell proliferation ultimately retarding prostate tumor formation.
Conclusion
Our data lucidly evidence the chemopreventive merits of dietary phytochemicals curcumin and PEITC in suppressing prostate adenocarcinoma.
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