Prognostic Value of Immunohistochemical Expression of Beta-1 Integrin in Pancreatic Carcinoma

<i>Background: </i>Prognostically relevant factors based on the histological assessment of the resected pancreas are known. However, the knowledge of additional factors associated with the prognosis is helpful in planning the therapy for an individual patient. β<sub>1</sub> Integrin expression is known to have a prognostic influence in some malignant tumors. No data are, however, available on the prognostic value of β<sub>1</sub> integrins in pancreatic carcinoma. <i>Method: </i>We investigated paraffin-embedded specimens of 19 patients undergoing surgical treatment for periampullary carcinoma and of 42 patients for ductal pancreatic carcinoma…

Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy

Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome-based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250-mediated immunotherapy. Flow cytometry revealed G250 surface expression in approxi…

MP-02.13 Oncological Long-Term Outcome of Patients Presenting With Chromophobe in Comparison to Non-chromophobe Renal Cell Carcinoma

Characterization of PD-1 and PD-L1 Expression in Papillary Renal Cell Carcinoma: Results of a Large Multicenter Study

Abstract Background Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce. Patients and Methods Patients’ sample collection was a joint collaboration of the nationwide PANZAR consortium – a multicenter study. Medical history and tumor specimens were collected from 245 and 129 patients with pRCC types 1 and 2, respectively. Expression of PD-1 and PD-L1 was determined by immunohistochemistry in pRCC and tumor-infiltrating mononuclear cells. Results Of 374 pRCC specimens, 204 type 1 and 97 type 2 we…

UP-01.160 Long-Term Follow-Up Is Necessary for Patients Presenting With pT1 and pT2 Renal Cell Carcinoma

Targeting of tumor associated antigens in renal cell carcinoma using proteome-based analysis and their clinical significance

The suitability of proteome-based strategies for the targeting of tumor-associated markers along with further analysis regarding their clinical significance were investigated in human renal cell carcinoma (RCC). The immunogenic protein expression profile of normal kidney and RCC cell lines was studied by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, also termed PROTEOMEX. Employing this approach, a series of proteins reactive with either RCC patient sera and/or reactive with control sera were identified by microanalysis of tryptic peptides. Some of these candidate antigens represent members of the cytoskeletal family, such as cytokeratins, i…

Oncologic Long-term Outcome of Elective Nephron-sparing Surgery Versus Radical Nephrectomy in Patients With Renal Cell Carcinoma Stage pT1b or Greater in a Matched-pair Cohort

Objectives To analyze the oncologic outcome and overall survival (OS) for patients with renal cell carcinoma (RCC) >4 cm undergoing radical nephrectomy (RN) or elective nephron-sparing surgery (NSS) in a matched-pair cohort. Methods From 1988 to 2007, we identified 829 patients in our clinic treated with either RN (n = 641) or open NSS (n = 188) for renal masses >4 cm. After matching the cohort for age, time of surgery, grade, TNM stage, tumor size, and sex and excluding patients with metastases, benign lesions with an imperative indication, and those with missing records, 173 remained for oncologic analysis. OS, cancer-specific survival, and progression-free survival were estimated using t…

Intraoperative peripheral frozen sections do not significantly affect prognosis after nerve-sparing radical prostatectomy for prostate cancer

Study Type – Therapy (outcomes research) Level of Evidence 2b What’s known on the subject? and What does the study add? We hypothesized that taking intraoperative frozen section (FS) biopsies of the peripheral margins of resection during radical prostatectomy would allow an intraoperative systematic scan of resection margins. In the case of positive FS, extended resection could be performed with the aim of completely excising residual tumour, improving biochemical recurrence-free survival of patients with positive surgical margins at the inked specimen. To our knowledge, the prognostic value of achieving a negative resection status by systematically taking intraoperative FS of the periphera…

Analysis of the structural integrity of the TAP2 gene in renal cell carcinoma.

The transporter associated with antigen processing (TAP) gene products is involved in the processing of endogenous peptides that bind to MHC class I molecules. Mutations and/or polymorphism within these genes could alter the efficacy of the immune response which might be relevant for the development of autoimmune diseases and cancer. In this study we examined both the structural integrity and the polymorphism of TAP2 in renal cell carcinoma lesions by sequencing TAP2 in renal cell carcinoma lesions and autologous normal kidney epithelium. TAP2 sequence analysis of 31 renal cell carcinoma lesions, one oncocytoma and respective autologous normal kidney epithelium revealed no mutation in the T…

KDM5B and CBX5 as potential tumor-associated immunogenic antigens in triple-negative breast cancer (TNBC)

UP-01.148 E2EPF as an Ubiquitin Carrier Protein Plays a Role in the Cancer Genesis of Papillary Renal Cell Carcinoma

MP-02.07 Calcium Depending Bone Metastases in Renal Cell Carcinoma

Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines

Background Radioresistance is a common feature of head and neck squamous cell carcinoma (HNSCC). We previously showed that the irradiation- activated vascular endothelial growth factor (VEGF)-extracellular signal-regulated kinase (ERK)-axis is fundamental for the survival of resistant tumors. In this study, we examined if treatment with potent multikinase (MK) inhibitors, sorafenib and sunitinib, could radiosensitize tumor cells. Methods Cultured HNSCC cell lines were treated with inhibitors and subsequently irradiated. Radiosensitizing effects were functionally assessed by annexin-V apoptosis and clonogenic assays and confirmed by Western blot. Additionally, we surveyed human HNSCC tissue …

Zinc overload mediated by zinc oxide nanoparticles as innovative anti-tumor agent

The predicted global cancer burden is expected to surpass 20 million new cancer cases by 2025. Despite recent advancement in tumor therapy, a successful cancer treatment remains challenging. The emerging field of nanotechnology offers great opportunities for diagnosis, imaging, as well as treatment of cancer. Zinc oxide nanoparticles (ZnO NP) were shown to exert selective cytotoxicity against tumor cells via a yet unknown mechanism, most likely involving the generation of reactive oxygen species (ROS). These nanoparticles are a promising therapeutic opportunity as zinc is a nontoxic trace element and its application in medically-related products is considered to be safe. We could show that …

Enhanced expression of ELAM-1 on endothelium of renal cell carcinoma compared to the corresponding normal renal tissue

Abstract Renal cell carcinoma (RCC) has been shown to respond to an immunological therapy with tumor infiltrating lymphocytes (TIL), which accumulate in RCC at a higher density than in normal renal tissue, suggesting that there is selective tumor invasion. Since invasion of TIL into the malignant tissue is mediated by adhesion molecules, we examined the different expression of the adhesion molecule endothelial-leukocyte-adhesion-molecule-1 (ELAM-1) on endothelial cells of RCC versus normal renal tissue. For a specific quantification, the level of ELAM-1 mRNA was investigated by both semi-quantitative reverse transcription–polymerase chain reaction (RT–PCR) and Northern blot analysis and ref…

Impact of several histopathological prognosticators and local tumour extension on oncological outcome in pT3b/c N0M0 renal cell carcinoma.

OBJECTIVE To investigate the prognostic relevance of different histopathological features and local tumour extension in patients with pT3b/c N0M0 renal cell carcinoma (RCC), as recently new proposals of reclassifying tumour fat invasion in pT3b/c RCC have been made but the effect of other histopathological tumour characteristics and combinations thereof with tumour invasion has yet to be determined in these patients. PATIENTS AND METHODS Between 1990 and 2006, 1943 patients underwent surgical treatment for renal tumours in our institution, of which 175 patients (8.7%) had pT3b/c RCC. After exclusion of 57 patients (32.6%) with lymph node and/or distant metastases at the time of diagnosis, 1…

Ubiquitin COOH-Terminal Hydrolase 1: A Biomarker of Renal Cell Carcinoma Associated with Enhanced Tumor Cell Proliferation and Migration[?Q1: Running head: UCHL1, a Biomarker of RCC. Short title OK?Q1]

Abstract Purpose: Renal cell carcinoma (RCC) accounts for 2% to 3% of all malignancies. It represents one of the most radiation- and chemotherapy-resistant tumors and surgical resections are only effective in organ-defined disease. However, RCC is an immunogenic tumor with response rates to immunotherapies between 10% and 20% of the treated patients. Due to the currently inefficient therapies and the low 5-year survival rates of RCC patients, novel diagnostic, prognostic, and therapeutic markers are urgently needed for this disease. Experimental Design: Proteome-based approaches were used to identify (a) differentially expressed proteins in RCC compared with normal kidney epithelium and (b)…

Perioperative morbidity and renal function in young and elderly patients undergoing elective nephron-sparing surgery or radical nephrectomy for renal tumours larger than 4 cm

Objective To analyse renal function, perioperative morbidity and overall survival (OS) in patients aged 65 years treated by radical nephrectomy (RN) or elective nephron-sparing surgery (NSS) for renal tumours > 4 cm. Patients and methods From our database, we identified 829 patients with renal tumours > 4 cm treated by either RN (n = 641) or NSS (n= 188) at our institution between 1981 and 2007. After excluding patients with imperative indication and metastases, we identified retrospectively 81 patients aged 65 years (elderly patients) treated for renal tumours > 4 cm. In all, 36 and 33 patients underwent NSS and 45 and 52 patients underwent RN in the young and elderly group, respectively. …

Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer

There is still a great unmet medical need concerning diagnosis and treatment of breast cancer which could be addressed by utilizing specific molecular targets. Tumor-associated MUC1 is expressed on over 90 % of all breast cancer entities and differs strongly from its physiological form on epithelial cells, therefore presenting a unique target for breast cancer diagnosis and antibody-mediated immune therapy. Utilizing an anti-tumor vaccine based on a synthetically prepared glycopeptide, we generated a monoclonal antibody (mAb) GGSK-1/30, selectively recognizing human tumor-associated MUC1. This antibody targets exclusively tumor-associated MUC1 in the absence of any binding to MUC1 on health…

Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptorCXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence ofCXCR4 expression on the progression of human renal cell carcinoma.CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity ofCXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities ofCXCR4 expression. StrongCXCR4 expression of renal cell carcinoma was si…

Pain experience and social support of endometriosis patients during the COVID-19 pandemic in Germany – results of a web-based cross-sectional survey

Background Endometriosis is a chronic pain condition in premenopausal women. Pain is mainly characterized by pain intensity and may induce disability in all areas of daily life. Nevertheless, pain is influenced by emotional and social factors as well. Social distancing measures or quarantine, as reaction to rapidly rising infections with the COVID-19 virus due to the SARS-CoV-2 pandemic, were implemented across Europe to prevent the spread of the virus and social distancing measures were imposed by the German government by beginning of March 2020 with initiation of the lockdown by the end of March 2020. The objective of this study was to assess, how social distancing measures during the lo…

Tissue engineered pre-vascularized buccal mucosa equivalents utilizing a primary triculture of epithelial cells, endothelial cells and fibroblasts

Artificial generated buccal mucosa equivalents are a promising approach for the reconstruction of urethral defects. Limiting in this approach is a poor blood vessel supply after transplantation, resulting in increased morbidity and necrosis. We generated a pre-vascularized buccal mucosa equivalent in a tri-culture of primary buccal epithelial cells, fibroblasts and microvascular endothelial cells, using a native collagen membrane as a scaffold. A successful pre-vascularization and dense formation of capillary-like structures at superficial areas was demonstrated. The lumen size of pre-formed blood vessels corresponded to the capillary size in vivo (10-30 μm). Comparing native with a highly …

Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-&gamma

The impact of intercellular communication for the generation of complex multicellular prevascularized tissue equivalents

In reconstructive surgery the use of prevascularized soft tissue equivalents is a promising approach for wound coverage of defects after tumor resection or trauma. However, in previous studies to generate soft tissue equivalents on collagen membranes, microcapillaries were restricted to superficial areas. In this study, to understand which factors were involved in the formation of these microcapillaries, the levels of the angiogenic factors vascular endothelial growth factor (VEGF), Interleukin-8 (IL-8), and basic fibroblast growth factor (bFGF) in the supernatants of the tissue equivalents were examined at various time points and conditions. Additionally, the influence of these factors on …

Low-frequency extracorporeal shock wave lithotripsy improves renal pelvic stone disintegration in a pig model.

OBJECTIVE To compare disintegration rates for renal stones treated by 60 vs 120 shock waves (SW)/min at the same energy settings, using standardized validated artificial stones in a pig model. MATERIALS AND METHODS Gypsum artificial stones (13 × 6 mm) were inserted into the renal pelvis on either side of 12 anaesthetized pigs by open surgery. Extracorporeal SW lithotripsy (ESWL) was applied using a new electromagnetic lithotripter (Lithoskop®, Siemens AG Healthcare, Munich, Germany) at 60 and 120 SW/min; 3000 SW were applied to each kidney with the same energy settings. Stone fragments were collected after nephrectomy, passed through calibrated test sieves, and weighed. Fragment size catego…

The role of extracellular calcium in bone metastasis

AbstractThis review summarizes the role of extracellular calcium, as found present in the bone tissue, in the process of bone metastasis.

UP-01.200 Oncological Long-Term Results of Elective Nephron-Sparing Surgery versus Radical Nephrectomy for Renal Tumours Larger Than 4cm

Bone Metastasis in Renal Cell Carcinoma is Preprogrammed in the Primary Tumor and Caused by AKT and Integrin α5 Signaling

Bone metastasis develops in 30% of all patients with renal cell carcinoma. We elucidated the mechanisms that lead to and predict bone metastasis of renal cell carcinoma.Nine renal cell carcinoma primary cell lines and 30 renal cell carcinoma tissue specimens (normal and tumor tissue) were collected from 3 patients with no metastasis and 10 with lung or bone metastasis within 5 years after nephrectomy. Cell migration was analyzed in a Boyden chamber and proliferation was assessed by bromodeoxyuridine incorporation. Adhesion to fibronectin, and collagen I and IV was determined after cell staining. The expression and/or activity of cellular signaling molecules was quantified by Western blot.Co…

Heat shock protein expression and anti-heat shock protein reactivity in renal cell carcinoma.

Heat shock proteins (HSP) are families of highly conserved proteins which are induced in cells and tissues upon exposure to extreme conditions causing acute or chronic stress. They exhibit distinct functions and have been implicated in the pathogenesis of a number of diseases, including cancer. A causal relationship between HSP expression and immunogenicity has been demonstrated in murine and human tumors and is also associated with the immune response. In order to investigate the correlation of HSP expression and their immunogenic potential in renal cell carcinoma (RCC), we here analyzed (i) the protein expression profile of various members of the HSP family in untreated and interferon (IF…

A retrospective analysis of immunohistochemical determined IRF4 (interferon regulating factor 4) expression in a consecutive cohort of 114 ovarian cancer patients

Identification of fatty acid binding proteins as markers associated with the initiation and/or progression of renal cell carcinoma

Renal cell carcinoma (RCC) representing the most common neoplasia of the kidney in Western countries is a histologic diverse disease with an often unpredictable course. The prognosis of RCC is worsened with the onset of metastasis, and the therapies currently available are of limited success for the treatment of metastatic RCC. Although gene expression analyses and other methods are promising tools clarifying and standardizing the pathological classification of RCC, novel innovative molecular markers for the diagnosis, prognosis, and for the monitoring of this disease during therapy as well as potential therapeutic targets are urgently needed. Using proteome-based strategies, a number of RC…

High proliferation rate and TNM stage but not histomorphological subtype are independent prognostic markers for overall survival in papillary renal cell carcinoma

Papillary renal cell carcinoma (PRCC) is currently divided in 2 subtypes. We reviewed a large cohort of PRCC and correlated subtype, morphological features and diagnostic marker expression with overall survival (OS) to uncover differences between the 2 subtypes. Three hundred seventy-six renal tumors initially diagnosed as PRCC with clinical and survival data were collected from the participating centers. Two hundred forty-six tumors were classified as PRCC1 (65.4%) and 130 as PRCC2 (34.6%) and graded according to the 2016 World Health Organization/International Society of Urological Pathology grading system. Morphological features (abundant cytoplasm, necrosis, fibrous stroma, foamy macrop…

Migration of renal tumor cells depends on dephosphorylation of Shc by PTEN.

The tumor suppressor PTEN is a phosphatase using FAK and Shc as direct substrates, and Akt as a key effector via PIP3. PTEN regulates cell migration and may influence metastases. We quantified PTEN in 135 clear cell renal cell carcinomas (ccRCC) by Western blot analysis and found statistically significant lower PTEN expression in patients who died, usually caused by metastases, within 5 years after surgery, compared to those surviving this time period. In athymic mice, PTEN transfected 786-O cells were injected into the tail vein and metastatic load of the lungs was quantified. We observed a strongly reduced metastatic load after PTEN transfection. For analyses of the PTEN activities, trans…

(TA)MUC1 as a potential new target for breast cancer therapy

Angiotensin type 2 receptor is important in the normal development of the ureter

In humans, the actions of angiotensin II are transduced through the AT1 and AT2 receptors which have recently been implicated in renal organogenesis. Polymorphisms in the human angiotensin II receptor genes have been linked to cardiovascular and nephrological disorders. In this study we evaluated 35 patients with either primary obstructive megaureter or posterior urethral valves. Each was genotyped for the A1166 AT1 polymorphism and the recently described A-1332G AT2 transition. The incidence of these genetic variants was also evaluated in normal controls without any ultrasonographic urological abnormalities. Similar to our previous findings in congenital urological abnormalities, the AT1 r…

Interferon-beta: a therapeutic for autoimmune lupus in MRL-Faslpr mice.

Type I interferons are associated with lupus. Genes that are regulated by IFN-alpha are upregulated in pediatric lupus patients. Gene deletion of the IFN-alpha/beta receptor in experimental lupus-like NZB mice results in reduced disease activity. Conversely, IFN-beta is a well-established treatment in multiple sclerosis, another autoimmune disease. For determining whether IFN-beta treatment is harmful or beneficial in lupus, MRL-Fas(lpr) mice were injected with this type I IFN. Treatment was initiated in MRL-Fas(lpr) mice with mild and advanced disease. IFN-beta was highly effective in prolonging survival and ameliorating the clinical (renal function, proteinuria, splenomegaly, and skin les…

256 Functional analysis of elective nephron-sparing surgery versus radical nephrectomy for renal tumors larger than 4 cm

Objective To preserve renal function, nephron sparing surgery (NSS) for renal tumors should be performed. Little is known about perioperative morbidity and long-term functional outcome of patients after elective NSS compared with radical nephrectomy (RN) in renal tumors >4 cm. Materials and Methods Eight-hundred twenty-nine patients were treated with either RN (n = 641) or NSS (n = 188) for renal tumors >4 cm. After pairing the cohort for age, grading, TNM, size, gender, and preoperative renal function and excluding patients with imperative indication and metastases, 247 patients remained for functional analysis. Serum creatinine (SCr) values were used to estimate glomerular filtration rate…

DNA repair protein O6-methylguanine-DNA methyltransferase in testis and testicular tumors as determined by a novel nonradioactive assay

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT, alkyltransferase) is an important suicide enzyme involved in defense against O6-alkylating endogenous metabolites and environmental carcinogens. It also plays a pivotal role in primary and acquired resistance of tumors to alkylating anticancer drugs targeting the O6-position of guanine (i.e., methylating and chloroethylating agents). MGMT can thus be considered a crucial biomarker for individual susceptibility to alkylating carcinogens and tumor drug resistance. This implies a need for a fast and convenient method for determination of MGMT. Routinely, MGMT is being quantified by radioactive assays which are relatively labo…

DHH is an independent prognosticator of oncologic outcome of clear cell renal cell carcinoma.

Aberrant HH signaling has proved important in the pathogenesis of several solid cancers. Limited in vitro analyses suggested an oncogenic role for HH in renal cell carcinoma. In this explorative study we sought to validate aberrant HH expression in patients with renal cell carcinoma.A tissue microarray was constructed from 140 radical nephrectomy specimens of patients with clear cell renal cell carcinoma. We performed immunohistochemistry for Ki67 and HH pathway biomarkers, including PTCH1, Smo, SHH, IHH, DHH, Gli1, Gli2 and Gli3. Staining intensity was measured by automated image processing and related to tumor stage and grade. The impact of biomarker expression on cancer specific survival…

Downregulation of β2-microglobulin in human cord blood somatic stem cells after transplantation into livers of SCID-mice: an escape mechanism of stem cells?

Adherently growing, non-hematopoietic somatic stem cells isolated from human cord blood were stained with the fluorescent dye PKH26 and transplanted into livers of SCID-mice to examine a possible cell fate transition. Already 7 days after transplantation stem cells were well integrated into the liver tissue. Human albumin that was not expressed by the stem cells before transplantation was detectable in the host's livers after injection of cord blood stem cells. Human alpha1-antitrypsin was detectable in stem cells already before transplantation and remained positive in the mouse liver. The most interesting observation in this study was the downregulation of human beta2-microglobulin (beta2M…

Identification of metabolic enzymes in renal cell carcinoma utilizing PROTEOMEX analyses

Abstract PROTEOMEX, an approach which combines conventional proteome analysis with serological screening, is a powerful tool to separate proteins and identify immunogenic components in malignant diseases. By applying this approach, we characterized nine metabolic enzymes which were differentially expressed in renal cell carcinoma (RCC) cell lines and compared their expression profiles to that of normal kidney epithelium cells. Four of these proteins, superoxide dismutase (SODC), triosephosphatase isomerase (TPIS), thioredoxin (THIO) and ubiquitin carboxyl-terminal hydrolase (UBL1) were further analysed for both their constitutive and interferon (IFN)-γ inducible protein expression pattern i…

Superior antitumor in vitro responses of allogeneic matched sibling compared with autologous patient CD8+ T cells.

AbstractAllogeneic cell therapy as a means to break immunotolerance to solid tumors is increasingly used for cancer treatment. To investigate cellular alloimmune responses in a human tumor model, primary cultures were established from renal cell carcinoma (RCC) tissues of 56 patients. In three patients with stable RCC line and human leukocyte antigen (HLA)-identical sibling donor available, allogeneic and autologous RCC reactivities were compared using mixed lymphocyte/tumor cell cultures (MLTC). Responding lymphocytes were exclusively CD8+ T cells, whereas CD4+ T cells or natural killer cells were never observed. Sibling MLTC populations showed higher proliferative and cytolytic antitumor …

The Impact of Insulin on Low-dose Metronomic Vinorelbine and Mafosfamide in Breast Cancer Cells

Background/aim Breast cancer (BC) may be affected by diabetes and anti-diabetic medication, as well as its therapeutic agents. Low-dose metronomic chemotherapy (LDMC) is an available treatment option in BC. We investigated the impact of insulin on low-dose metronomic vinorelbine and mafosfamide in BC cell lines. Materials and methods Human BC cell lines T-47D, MCF-7, MDA-MB-231, BT-549 and non-tumorigenic breast cell line MCF-10A were exposed to 0.01 μg/ml and 10 μg/ml insulin in combination with low-dose metronomic vinorelbine or mafosfamide. The cell viability was determined after 24-72 hours using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results Insulin, especi…

Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP wit…

Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid.

Abstract Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells. Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination. Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUC1, and clinical trials with tumor-associated MUC1 yielded unsatisfac…

Differential inhibition of renal cancer cell invasion mediated by fibronectin, collagen IV and laminin.

Invasion of tumor cells into the extracellular matrix is an essential step in the formation of metastases in renal cancer. Cell adhesion molecules such as beta(1)-integrins, which bind to the RGD sequence (arginine-glycine-asparagine) and CD44 are involved in this process. We examined the invasion of a renal carcinoma cell line (CCF-RC1) into the extracellular matrix compounds fibronectin, collagen IV and laminin and the effect of TGFbeta and IFNgamma on this process. The inhibitory effect of an antibody against the beta(1)-subunit of integrins (CD29), as well as a pentapeptide including the RGD sequence, was also evaluated. A micro-chemotaxis chamber, including a polycarbonate membrane wit…

Prognostic Impact of Immunoglobulin Kappa C in Breast Cancer Patients Treated with Adjuvant Chemotherapy.

<b><i>Introduction:</i></b> Immunoglobulin κC (IGKC)-positive tumor-infiltrating plasma cells are associated with better prognosis in node-negative breast cancer patients without adjuvant systemic therapy. In the present study we evaluated the prognostic significance of IGKC in breast cancer patients treated with adjuvant chemotherapy ± tamoxifen. <b><i>Methods:</i></b> IGKC expression was immunohistochemically analyzed in 193 breast cancer patients who were treated with adjuvant chemotherapy, either with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) between 1993 and 2001 wit…

Migration of renal carcinoma cells is dependent on protein kinase Cδ via β1 integrin and focal adhesion kinase

Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. In order to identify a connection between PKC isoforms and tumor progression in renal cell carcinoma (RCC), the influence of PKC isoforms on cell migration, adhesion and proliferation and possible influences of the activity of integrins and focal adhesion kinase (FAK) were analyzed in RCC cells. The experiments were performed in the RCC cell line CCF-RC1 after pre-incubation of the cells with the PKC inhibitors GF109203X, GO6976, RO31-8220 and rottlerin. Cell migration and adhesi…

317 Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Introduction/Background* In high-grade serous ovarian cancer (HGSOC) an early intraperitoneal metastatic spread is common which determines the therapeutical approach and prognosis. Integrins may be involved in metastatic spread of HGSOC. In this study, integrin expression was examined in primary tumour and metastases of HGSOC. Methodology The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumour samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumour localisations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progressi…

Full‐thickness tissue engineered oral mucosa for genitourinary reconstruction: A comparison of different collagen‐based biodegradable membranes

Tissue engineering is a method of growing importance regarding clinical application in the genitourinary region. One of the key factors in successfully development of an artificially tissue engineered mucosa equivalent (TEOM) is the optimal choice of the scaffold. Collagen scaffolds are regarded as gold standard in dermal tissue reconstruction. Four distinct collagen scaffolds were evaluated for the ability to support the development of an organotypical tissue architecture. TEOMs were established by seeding cocultures of primary oral epithelial cells and fibroblasts on four distinct collagen membranes. Cell viability was assessed by MTT-assay. The 3D architecture and functionality of the ti…

Primary Mucosal Epithelial Cell Cultivation: A Reliable and Accelerated Isolation

We illustrate a reliable and accelerated isolation routine for mucosal epithelial cells, which thereupon can be used for soft tissue engineering. This is highly important in the field of soft tissue engineering because mucosal equivalents are frequently usable in several surgical fields like gynecology, urology, otorhinolaryngology, ophthalmology, maxillofacial surgery, and many others. In this context the isolation of mucosal epithelial cells suitable for tissue engineering is mandatory. The reliable cultivation of mucosal or skin epithelial cells is challenging and there is currently no reproducible method. We demonstrate a solution for this problem by developing an accelerated and nevert…

Short-Term Functional and Oncologic Outcomes of Nephron-Sparing Surgery for Renal Tumours ≥7cm

Abstract Background Nephron-sparing surgery (NSS) for renal tumours preserves renal function and has become the standard approach for small renal tumours. Little is known about perioperative and oncologic outcomes of patients following NSS in renal tumours ≥7cm in the presence of a healthy contralateral kidney. Objective To analyse oncologic outcomes and perioperative morbidity in patients treated by NSS for renal tumours ≥7cm. Design, setting, and participants In total, 5767 patients were treated for renal tumours at two institutions from 1984 to 2009. In 91 patients, elective NSS was performed for renal tumours ≥7cm. Measurements Complication rates were assessed in detail and stratified u…

Deregulation of E2-EPF Ubiquitin Carrier Protein in Papillary Renal Cell Carcinoma

Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expressio…

Identification and analysis of tumor-associated antigens in triple-negative breast cancer (TNBC)

Single center comparison of anastomotic strictures after radical perineal and radical retropubic prostatectomy.

OBJECTIVES To analyze the incidence and management of anastomotic strictures (ASs) after radical perineal prostatectomy (RPP) and retropubic prostatectomy (RRP) and to identify possible predisposing factors. METHODS Between 1997 and 2007, we performed 866 RPP and 2052 RRP for localized prostate cancer. Median follow-up was 52 months (12-136). We analyzed preoperative serum prostate-specific antigen, prostate size, clinical and pathologic tumor stage, neoadjuvant hormone deprivation, previous transurethral resection of the prostate, transfusion requirement, anastomotic insufficiency, and acute urinary retention (AUR) and its subsequent management to identify possible predisposing factors for…

Loss of tumor suppressor protein PTEN during renal carcinogenesis

The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) encodes a dual specific protein and phospholipid phosphatase that affects cell proliferation, apoptosis and migration. In our study, we examined protein expression of PTEN in renal carcinogenesis. PTEN protein levels were examined in 42 clear cell renal cell carcinomas (ccRCC) and oncocytomas as well as in the corresponding normal renal tissue of the same patients using Western blot analysis. Cellular localization was analyzed by immunohistochemistry. PTEN was highly expressed in all investigated normal renal tissue specimens. Immunohistochemical analysis showed an almost exclusive staining of proxi…