Cutaneous Anomalies of the Critically Ill Patient.

Critically ill patients are at high risk for organ failure, including that of the integumentary system. Nurses working in intensive care are adept at performing comprehensive assessments that include the skin. Although pressure injury is a well-known complication associated with critical illness, patients may also have debilitating and life-threatening dermatoses.

Practice Dilemmas: Conditions That Mimic Pressure Ulcers/Injuries- To Be or Not To Be?

Background: Pressure ulcers/injuries (PU/Is) negatively affect patients by causing pain and increasing morbidity and mortality risks. Care teams have a heightened sense of awareness of the condition and may feel confident in their ability to appropriately identify and manage PU/Is, but the potential for, and consequences of, a misdiagnosis always should be considered.

Purpose: The purpose of this compendium is to describe and illustrate conditions that may mimic PU/Is.

Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers.

Background: Ribonucleotide reductase (RR) is an essential enzyme involved in DNA synthesis. We hypothesized that RR subunit M2 (RRM2) might be a novel prognostic and predictive biomarker for estrogen receptor (ER)-negative breast cancers.

Methods: Individual and pooled survival analyses were conducted on six independent large-scale breast cancer microarray data sets; and findings were validated on a human breast tissue set (ZJU set).

Ribonucleotide reductase large subunit M1 predicts poor survival due to modulation of proliferative and invasive ability of gastric cancer.

Objectives: We aimed to investigate the prognostic value of RRM1 in GC patients.

Methods: A total of assessable 389 GC patients with clinicopathological and survival information were enrolled from City of Hope (COH, n = 67) and Zhejiang University (ZJU, n = 322). RRM1 protein expression was determined by immunohistochemistry on FFPE tissue samples.

Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.

Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections.

Amplification of FRS2 and activation of FGFR/FRS2 signaling pathway in high-grade liposarcoma.

Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown.

MicroRNA-657 promotes tumorigenesis in hepatocellular carcinoma by targeting transducin-like enhancer protein 1 through nuclear factor kappa B pathways.

Unlabelled: Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Dysregulation of miR-657 has been observed in several types of cancers, but its biological function is still largely unknown. Our results showed that miR-657 expression can be induced by hepatitis viral proteins and is significantly increased in hepatocellular carcinoma (HCC) tissues.

Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers.

The overexpression of RRM2 [RR (ribonucleotide reductase) small subunit M2] dramatically enhances the ability of the cancer cell to proliferate and to invade. To investigate further the relevance of RRM2 and CRCs (colorectal cancers), we correlated the expression of RRM2 with the clinical outcome of CRCs. A retrospective outcome study was conducted on CRCs collected from the COH [(City of Hope) National Medical Center, 217 cases] and ZJU (Zhejiang University, 220 cases).

Secreted protein acidic and rich in cysteines-like 1 suppresses aggressiveness and predicts better survival in colorectal cancers.

Purpose: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is an extracellular matrix glycoprotein with malignancy-suppressing potential. The hypothesis that SPARCL1 reduces cancer invasiveness and predicts better survival in colorectal cancers (CRC) was investigated.

Experimental Design: Stable SPARCL1 transfectants, RKO-SPARCL1, and corresponding vector control were constructed and implanted into nude mice to generate a mouse xenograft model of liver metastasis.

CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells.

Cancer stem cells (CSC) play critical roles in cancer initiation, progression, and therapeutic refractoriness. Although many studies have focused on the genes and pathways involved in stemness, characterization of the factors in the tumor microenvironment that regulate CSCs is lacking. In this study, we investigated the effects of stromal fibroblasts on breast cancer stem cells.

Biomarker identification with ligand-targeted nucleoprotein assemblies.

Aims: Since many biomarkers of both the tumor and its microenvironment are expected to involve differential expression of divalent proteins capable of protein or peptide ligand interaction, we are developing multivalent nanodevices for the identification of biomarkers in prostate cancer.

Patients & Methods: We compared a multivalent thioredoxin-targeted nanodevice with monovalent thioredoxin in binding to human prostate cell line(s) and freshly frozen tissue specimens obtained after resection from patients with biopsy-proven prostate cancer.

Conclusion: The nanodevice binds specifically with enhanced avidity to tumor microenvironment-associated stromal cells in prostate cancer tissue specimens.

Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers.

Purpose: This study aims to address the hypothesis that the high-mobility group A2 (HMGA2), an oncofetal protein, relates to survivability and serves as a prognostic biomarker for colorectal cancer (CRC).

Experimental Design: This is a retroprospective multiple center study. The HMGA2 expression level was determined by performing immunohistochemistry on surgical tissue samples of 89 CRCs from a training set and 191 CRCs from a validation set.

Phase II clinical trial of imatinib mesylate in therapy of KIT and/or PDGFRalpha-expressing Ewing sarcoma family of tumors and desmoplastic small round cell tumors.

Background: We have previously shown that the receptor tyrosine kinases, KIT and PDGFRalpha, are expressed on ESFT cell lines, and that imatinib induces dose-dependent apoptosis (1). We conducted a Phase II trial to evaluate the effectiveness of imatinib for patients with recurrent ESFT or DSRCT expressing KIT and/or PDGFRalpha.

Patients And Methods: Patients were selected for tumor immunohisto-chemical expression > or =2+/4+ for KIT or PDGFRalpha.

Antitumor activity of targeting SRC kinases in endothelial and myeloid cell compartments of the tumor microenvironment.

Purpose: Several Src family kinase (SFK) inhibitors have entered clinical trials based on their direct effects against tumor cells. Here, we characterize the effects of targeting Src kinases on the tumor microenvironment and how these effects influence tumor growth.

Experimental Design: Human cancer cells grown in cell culture or in mice were treated with dasatinib, a small-molecule inhibitor of SFKs.

Immunoglobulin light chain immunohistochemistry revisited, with emphasis on reactive follicular hyperplasia versus follicular lymphoma.

The identification of monotypic light chains is an important adjunct to the diagnosis of B-cell lymphoma, yet to reliably perform it on formalin-fixed paraffin sections is often difficult. We have evaluated a new set of monoclonal antibodies to kappa and lambda light chains that are reactive in paraffin sections. In reactive lymphoid tissues, polytypic staining was noted in greater than 95% of cases, with strong staining of plasma cells, moderate staining of the follicular dendritic cell network, and weak staining of mantle zone cells.

Protein kinase A activation confers resistance to trastuzumab in human breast cancer cell lines.

Purpose: Trastuzumab is a monoclonal antibody targeted to the Her2 receptor and approved for treatment of Her2-positive breast cancer. Among patients who initially respond to trastuzumab therapy, resistance typically arises within 1 year. BT/Her(R) cells are trastuzumab-resistant variants of Her2-positive BT474 breast cancer cells.

Overlapping features between dedifferentiated liposarcoma and undifferentiated high-grade pleomorphic sarcoma.

Dedifferentiated liposarcoma (DDL), occurring in up to 10% of well differentiated liposarcoma cases, has similar histologic features to that of undifferentiated high-grade pleomorphic sarcoma (UHGPS); the former develops in a background of atypical lipomatous tumors/well differentiated liposarcoma, whereas the latter shows no specific line of differentiation. The retroperitoneum and thigh represent the most common anatomic locations for both the sarcomas. Despite their morphologic similarity, the issue of whether these 2 sarcomas share overlapping immunohistochemical and molecular features has not been well studied.

Human papillomavirus infection as a prognostic factor in oropharyngeal squamous cell carcinomas treated in a prospective phase II clinical trial.

Unlabelled: The aim of this study was to determine the presence of high-risk HPV-16 in patients with HNSCC, assess the impact of HPV status on treatment response and survival in this select cohort treated with combined modality therapy and to identify the differences in HIF-1alpha and VEGF expression in HPV-positive and -negative tumors.

Patients And Methods: Patients had resectable, untreated stage III, IV HNSCC of the oral cavity, oropharynx, hyopharynx or larynx, and stage II cancer of the base of tongue, hypopharynx and larynx. HPV status was determined by conventional PCR in fresh frozen biopsy samples and by Taqman PCR assay on formalin-fixed, paraffin-embedded specimens.

LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat.

Aims/hypothesis: Previous studies have shown that LR-90, a new inhibitor of AGE formation, prevented the development of experimental type 1 diabetic nephropathy. In this study, we examined the effects of LR-90 in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes and metabolic syndrome, and investigated the mechanisms by which it may protect against renal injury.

Methods: Male ZDF rats were treated without or with LR-90 from age 13 to 40 weeks.

Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry.

Distinguishing a well-differentiated hepatocellular carcinoma (HCC) from normal and cirrhotic liver tissue or benign liver nodules, such as hepatic adenoma (HA) and focal nodular hyperplasia (FNH), may be very difficult in some cases, particularly in small needle core biopsies. We studied the expression of Glypican-3 (GPC3) and CD34 in 107 cases of HCC, 19 cases of HA, and 16 cases of focal nodular hyperplasia (FNH). In addition, we studied GPC3 expression in 225 cases of nonhepatic human tumors with epithelial differentiation.

II. Cesium leaching in CsA and CsX zeolites: use of blocking agents to inhibit the cesium cation mobility.

Cesium-exchanged A and X zeolites were loaded with cesium acetate species and thermally treated in order to inhibit the mobility of exchangeable cesium cations. The proposed procedure seems to block the cavities channels avoiding the releasing of cesium cations under the leaching conditions. The cesium impregnated species did not induce strong structural modifications if they are used in small amounts (0.

Lineage determination of CD20- B-Cell neoplasms: an immunohistochemical study.

We studied 61 CD20- B-cell lymphomas, including 29 cases of precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/B-LBL), 25 cases of CD20- recurrent mature B-cell lymphoma after rituximab therapy, and 7 cases of CD20- diffuse large B cell lymphoma (DLBCL). We used markers specific for B lineage: CD79a, Pax-5, OCT.2, and BOB.

Renoprotective and lipid-lowering effects of LR compounds, novel advanced glycation end product inhibitors, in streptozotocin-induced diabetic rats.

The accelerated formation of advanced glycation/lipoxidation end products (AGEs/ALEs) has been implicated in the pathogenesis of various diabetic complications. Several natural and synthetic compounds have been proposed and advanced as inhibitors of AGE/ALE formation. We examined the effects of two new AGE/ALE inhibitors, LR-9 and LR-74, on the prevention of early renal disease and dyslipidemia in streptozotocin (STZ)-induced diabetic rats.

Prevention of early renal disease, dyslipidaemia and lipid peroxidation in STZ-diabetic rats by LR-9 and LR-74, novel AGE inhibitors.

Background: Increased formation of advanced glycation/lipoxidation endproducts (AGEs/ALEs) has been implicated in the pathogenesis of various diabetic complications. Several compounds have been developed as inhibitors of AGE/ALE formation. We examined the effects of two new AGE/ALE inhibitors, LR-9 and LR-74, on the development of early renal disease and lipid metabolism in streptozotocin (STZ)-induced diabetic rats.