Role of Notch, IL-1 and leptin expression in colorectal cancer.

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1ß, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer.

Foreign Body Reaction to Dialysis Chatheter and Peritoneal Fluid Eosinophilia in a Child on Continuous Ambulatory Peritoneal Dialysis.

Foreign body reaction is a tissue response against implanted materials. We described for the first time the eosinophilic peritonitis and foreign body giant cell reaction to dialysis catheter in a nonatopic child on continuous ambulatory peritoneal dialysis. We found tenderness, redness, and swelling without purulent discharge around the peritoneal catheter; increased eosinophil count in cloudy dialysis fluid; and blood and hyperechoic granulomatous formation appearance surrounding the peritoneal catheter on ultrasonography and foreign body giant cell reaction to dialysis catheter in pathologic examination of granulomatous lesionin in our patient. The peritoneal dialysis catheter was removed due to resistance to antibiotic and antihistamine treatments for suspected peritonitis and tunnel infection. Foreign body reaction and eosinophilic peritonitis with eosinophilic cloudy dialysis effluent can exist simultaneously. Foreign body reaction should be considered in the differential diagnosis of exit site and/or tunnel infection. Ultrasonography helps distinguish between foreign body reaction and exit-site or tunnel infection.

An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

IDH1 mutations is prognostic marker for primary glioblastoma multiforme but MGMT hypermethylation is not prognostic for primary glioblastoma multiforme.

PURPOSE: To establish the frequency of IDH1 mutations and MGMT methylation in primary glioblastomas. EXPERIMENTAL DESIGN: We screened primary glioblastoma multiforme (GBM) in a population-based study for IDH1 mutations and MGMT methylation and correlated them with clinical data. RESULTS: IDH1 mutations were detected in 5 of 40 primary glioblastomas (12,5%). Primary GBM patients carrying IDH1 mutations were significantly younger, mean age of 41±5.06years, than patients with wild-type IDH1, mean age of 57±2,29years, p=0.011. The mean survival time of all GBM patients with and without IDH1 mutations was 19months (5 cases) and 16months (35 cases), respectively (p>0,05). MGMT methylation was detected in 13 of the 40 patients (32,5%). MGMT-promoter methylation did not correlate with overall survival (OS; p>0,05). CONCLUSION: In summary, our study is the first study to investigate the IDH1 mutation status and MGMT methylation in primary GBMs in Turkish population and confirmed IDH1 mutation as a genetic marker for also primary GBMs. Our data are still insufficient for definite ascertainment; and our preliminary results suggest: IDH1 status shows an association with younger age and there is a lack of association between IDH1 mutation and survival time. Furthermore MGMT promoter methylation had no prognostic value and lower frequency in primary glioblastomas.

Giant Condyloma Acuminate Due to Human Papillomavirus Type 16 in an Infant Successfully Treated with Topical Imiquimod Therapy.

Anogenital warts related to human papillomavirus (HPV) have been observed in children. Definition of the transmission mode, therapy, and follow-up for long term potential complications is important. A 27-month old girl was admitted with multiple pedunculated red-purple colored cauliflower-like lesions of 1.5 years duration. Clinical/histopathological and microbiological diagnosis was condyloma acuminate due to HPV type 16. After 12 weeks of imiquimod 5% cream application (pea-sized) overnight three times per week, the perianal warts had completely disappeared. The mode of transmission of HPV 16 in our case was probably horizontal, related to the sharing of common personal hygiene items in the women's shelter. We report herein the case of an infant living in a women's shelter with giant condyloma acuminata due to HPV 16, which was successfully treated with topical imiquimod therapy. This patient should be followed up for recurrence and potential malignant lesions related to HPV type 16.

Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools.

Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.

Detection of kinase amplifications in gastric adenocarcinomas.

AIM: To determine the incidences of copy number aberrations of receptor kinases and their relations in Turkish patients with gastric adenocarcinoma. MATERIALS AND METHODS: The prevalence of genomic copy number aberrations of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/topoisomerase IIa (TOP2A), centrosome-associated kinase aurora A (AURK A), centrosome-associated kinase aurora B (AURK B), and mesenchymal-epithelial transition factor (MET) genes and polysomies of related chromosomes were analyzed by fluorescent in situ hybridization (FISH) in tumor samples from 35 patients with gastric cancer. RESULTS: There were 28.6%, 65.7%, 20.0%, 17.1%, 60.0%, and 45.7% cases considered FISH-positive for EGFR, MET, HER2, TOP2A, AURK A, and AURK B genes, respectively. Statistically significant associations were determined in detection of amplifications of 1) EGFR gene with chromosome 7 polysomy, 2) MET gene in nonpolysomic chromosome 7 nuclei, 3) HER2/TOP2A genes in nonpolysomic chromosome 17 nuclei, 4) coamplification of HER2/TOP2A in poorly differentiated carcinomas, and 5) AURK A gene in nonpolysomic chromosome 20 nuclei. Most of the aberrations were predominantly seen in poorly differentiated tumors, but a high rate of the amplified MET gene was also detected in moderately differentiated carcinomas. CONCLUSION: Chromosome 7 polysomy may be responsible for EGFR gene amplifications, and we concluded that MET and AURK A genes amplifications were commonly seen aberrations in gastric adenocarcinomas and may offer information about disease progression and administration of individualized treatment for gastric cancer patients.

Prognostic value of osteopontin in patients treated with primary radiotherapy for head and neck cancer.

BACKGROUND: The prognostic value of tumor osteopontin (OPN) in patients with squamous-cell head and neck cancer (SCHNC) was investigated. MATERIALS AND METHODS: OPN expression was assessed by immunohistochemical methods in 50 patients, who were treated with primary radiotherapy (RT) for locally advanced SCHNC. The effects of OPN on clinical parameters, local-regional control after RT and metastasis-free survival, was assessed. RESULTS: The rate of OPN expression in tumor tissue was 76%. OPN positive cases had lower Hb levels (p=0.088). Mean time to local recurrence was 53.8 months (SE 3.9) in OPN-negative cases and 39.1 months (SE 4.7) in OPN-positive cases (p=0.047). OPN increased the risk of local recurrence 5.9 times (p=0.085). It had no effect on metastasis-free (p=0.116) or overall survival (p=0.123). OPN was positive in 12 of 19 cases that developed grade 3-4 acute radiation dermatitis (p=0.096). CONCLUSIONS: OPN expression is associated with an increase in local recurrence in patients who were treated with primary RT for locally advanced SCHNC.

Necrotic ulcer: a manifestation of leukemia cutis.

A 71-year-old man presented to our dermatological clinic with a 3-month history of a wound on his leg. He complained of weakness for the past few months. On his dermatological examination he had a 3x3-cm necrotic ulcer on his left tibia (Figure 1). On physical examination, there was 1 x 1-cm axillary lymphadenopathy. There was no other lymph node enlargement, hepatosplenomegaly, or gingival hypertrophy. Peripheral blood results showed 2.4x103/mm3 leukocytes (normal range 4-11 x 103/mm3) with 66% neutrophils. The hemoglobin value was 10.1 g/dL (13-18 g/dL), and the platelet count was 63x103/mm3 (150-440 x 103/mm3). No blasts were detected in a peripheral blood smear. His lactate dehydrogenase level was 567 U/L (240-480 U/L). All other results of blood chemistry were within normal limits. Punch biopsy of the skin lesion showed ulceration and dense dermal acute and chronic inflammation. There was a superficial and deep perivascular and periadnexal infiltrate of neoplastic cells composed of relatively abundant eosinophilic cytoplasm and large nuclei with blastic chromatin and occasional small nucleoli (Figure 2). Mitotic figures were prominent. Immunohistochemical stains were performed, and the neoplastic cells were CD3, CD20, CD138, and S100 protein negative. Myeloperoxidase and CD68 were positive. The histopathological findings were consistent with leukemic infiltration. Examination of bone marrow biopsy revealed that the blastic cells constituted more than 20% of the bone marrow cellularity. Cytogenetic analysis of bone marrow aspiration with fluorescence in situ hybridization was negative for inversion 16, t(8;21) and t(15;7). Histochemical stains for myeloperoxidase, sudan black, periodic acid-Schiff, and alpha naphthyl acetate were also negative. Blastic cells were DR, CD13, CD117, and CD34 positive and CD5, CD7, CD10, CD14, CD19, CD20, CD33, CD41, CD56, CD64, and CD79 negative according to flow cytometry immunophenotyping. Blastic cells were 35% in the bone marrow. Based on the findings of bone marrow examination, the patient was diagnosed as having acute myeloblastic leukeamia (AML) with minimal differentiation (subtype MO) according to French-American-British and World Health Organization classification. The examination of abdominal ultrasonography and thorocic and abominal computed tomography revealed no metastases. The patient was treated with chemotherapy that consisted of cytarabin and daunorubicin. After chemotherapy, the lesion regressed. One month after chemotherapy, the patient presented to the hospital with a complaint of fever. He was diagnosed with febrile neutropenia. He died of cardiac failure 12 months after appearance of skin infiltration.

Differential expression of P16 and P21 in benign and malignant uterine smooth muscle tumors.

PURPOSE: The diagnosis of benign and malignant uterine smooth muscle tumors depends on morphologic criteria such as nuclear atypia, coagulative tumor cell necrosis and mitotic activity. Most of these tumors are readily classifiable into benign or malignant categories using these criteria. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. Hence, it would be useful to have additional markers which could help to distinguish these tumors. The aim of the study was to evaluate p16 and p21 expressions in uterine smooth muscle tumors and determine whether p16 and p21 have a potential value in the differential diagnosis of problematic cases. In addition, we evaluated whether the differential expression of p16 and p21 in uterine leiomyosarcomas correlated with tumor recurrence and patient survival. METHODS: p16 and p21 expressions were investigated by immunohistochemistry from paraffin-embedded tissues in 53 cases of uterine smooth muscle tumors consisting of 15 cases of leiomyoma, 14 cases of atypical leiomyoma (leiomyoma with bizarre nuclei), 3 cases of smooth muscle tumor of uncertain malignant potential (STUMP) and 21 cases of leiomyosarcoma. Cases were evaluated with respect to both staining percentage and intensity. RESULTS: There was a statistically significant difference in p16 and p21 staining percentage and intensity between leiomyosarcomas and the other groups. There was no difference in p16 and p21 expressions between leiomyomas, atypical leiomyomas (leiomyoma with bizarre nuclei) and STUMPs. Multivariate analysis showed that the tumor stage was the only independent significant prognostic factor for overall survival in leiomyosarcomas. Neither p16 nor p21 was correlated with disease-free or overall survival. CONCLUSIONS: Our findings suggested that p16 and p21 may be of value as an adjunct to conventional morphologic criteria in the assessment of problematic uterine smooth muscle tumors.

Multiple intradural-extramedullary ependymomas: proven dissemination by genetic analysis.

This 45-year-old woman was admitted with neck and back pain and difficulty in ambulation that had been progressively worsening for 2 years. Admission MR imaging revealed a cervicomedullary junction tumor and 2 intradural-extramedullary spinal tumors located separately at the levels of T5-6 and T8-9. All masses were successfully resected in a 2-stage operation. Histopathological examination of the surgical specimens revealed that all the lesions were ependymomas. Genetic analysis was performed to determine if the tumors were related. Conventional cytogenetics, multiplex fluorescence in situ hybridization (M-FISH), interphase-FISH specific to 22q11, and epidermal growth factor receptor loci analyses of the tumor samples revealed that the lesions originated from the same primary tumor. Although 3 simultaneous tumors in different compartments of the neural axis were diagnosed as ependymoma by histopathological examination, it was not possible to be sure if their multiplicity was due to spread of tumor cells via CSF or if it was due to multicentric foci. Thus, genetic analysis of the tumor samples is essential to confirm the exact mechanism of development of multiple ependymomas.

Diffuse uterine adenomatoid tumor in a patient with chronic hepatitis C virus infection.

Uterine adenomatoid tumors are usually solitary lesions. Adenomatoid tumors diffusely infiltrating the entire myometrium have rarely been reported in the literature. A feature common to half of the reported cases of diffuse uterine adenomatoid tumor was an immunocompromised status of the patient caused by the medications for renal transplantation. In this article, we describe an unusual case of diffuse uterine adenomatoid tumor in a patient with chronic hepatitis C virus infection. Pelvic examination showed an irregular and enlarged uterus. Supracervical hysterectomy and bilateral salpingo-oophorectomy was performed with a clinical diagnosis of uterine leiomyoma. Pathological examination showed, in addition to multiple leiomyomas, diffuse uterine adenomatoid tumor. We suggested that the diffuse pattern in our patient might be related to immunosuppression secondary to chronic hepatitis C virus infection.

Symptomatic foraminal extradural meningeal cyst.

The authors described the case of a 39-year-old man with Klippel-Trénaunay syndrome, who had an extradural meningeal cyst expanding into intervertebral foramen of lumbar 2 and 3 vertebrae. The patient suffered from low back pain radiating to the left lower extremity. Magnetic resonance imaging revealed a huge extradural meningeal cyst growing through intervertebral foramen far laterally. A widened neural foramen of L2 and L3 vertebrae was observed on his plain radiography. The cyst was totally excised after tying the ostium connecting the subarachnoid space of the dural sac. This case supports the congenital theory in the pathogenesis of spinal cysts because the Klippel-Trénaunay syndrome is a congenital disorder including a mesodermal abnormality which may be the causative factor for a congenital defect in dura.

Efficacy of prognostic factors on survival in patients with low grade glioma.

AIM: In this report, we aim to determine the prognostic factors influencing the length of survival in patients with low-grade gliomas. MATERIAL AND METHODS: In a retrospective evaluation, we have reviewed fiftythree patients who had been operated between the years of 1980 and 2006. The diagnoses of the patients were histopathologically verified as low-grade glioma(LGG). The medical records of the patients were reviewed for age, gender, tumor locations, extent of resection, and presence of seizure, the neurological status as defined by the Karnofsky Performance Scale (KPS) and radiotherapy treatment after surgery as possible prognostic factors. RESULTS: Median cumulative survival time for all the patients with LGG was 141+/-14.83 months. Median survival time was 216+/-78.52 months for astrocytoma Grade I; 115+/-8.22 months for astrocytoma Grade II, and 242+/-76.36 months for oligodendroglioma. Young age, histology subtype (oligodendroglioma) and preoperative KPS were determined to have positive influence on survival according to Log Rank Test. In contrast, age, histology type and the extent of resection remained independent prognostic factors upon survival when Cox Regression Backward Stepwise (Wald) method was performed. CONCLUSION: It can be concluded that surgery seems to be an appropriate first step option in the treatment of LGG.

PAP smear screening among married women living in Osamangazi University ALPU training area.

An inquiry including questions about socio-demographic and fecundity properties and covering the knowledge and attitudes of women about Pap smears was applied to 585 women living in Alpu district of Eskisehir, Turkey. Smear specimens were taken from 513 women and colpography was performed before and after acetic acid application with a digital camera. The women who had cervical lesions and/or aceto-white epithelium during the gynecological examination and/or had pathological findings in the smear and/or had suspicious findings at the colpography were invited (n=125, 24.4%) to the Department of Gynecology for colposcopic evaluation. Colposcopy was performed to 77 and biopsies were taken from 40 of the women during colposcopic examination. Of the biopsy specimens, 31 were accepted as benign while 9 were reported as pathology positive, one being high grade squamous intraepithelial lesion (HGSIL) and 8 low grade squamous intraepithelial lesion (LGSIL).

An unusual case of cervical clear-cell meningioma in pediatric age.

INTRODUCTION AND BACKGROUND: A 4-year-old girl was admitted with complaints of diplegia, right lower limb monoplegia, and left lower limb monoparesia. Cervical magnetic resonance imaging revealed an intradural-extramedullary tumor at the level of C1-C2. The tumor was resected totally. Histopathologic diagnosis revealed clear-cell meningioma. DISCUSSION: Intraspinal clear-cell meningioma (ICCM) is a rare aggressive variant of meningioma. There are only 25 cases reported to date, and only 13 of them are in pediatric age group. Of these 25 ICCM cases, only two are at cervical region. This report is the first ICCM case at upper cervical region (C1-C2) in both adult and pediatric age populations.

Peripheral intrapulmonary lipoma: a case report and review of the literature.

Lipomas are common benign tumours, but intrathoracic lipomas are rare and peripheral lung lipomas are exceptionally rare. Eight cases have been described in the world literature. We report a case of lipoma arising in the periphery of the left lower lung in a 54-year old woman. Grossly, it was presented as a well- circumscribed, thinly encapsulated, rounded, pale yellow mass. A wedge resection was done of the left lung and the microscopic findings revealed lipoma of the lung. The present paper recapitulates the macroscopic and microscopic features, the treatment and the differential diagnosis of this rare neoplasm.

Plasmacytoid myoepithelioma of the soft palate: a review of the literature and report of a case with immunohistochemical findings.

Myoepitheliomas of salivary glands are rare neoplasms, accounting for less than 1% of all salivary gland tumors. They are classified into four cell types: epithelioid, spindle, clear, and plasmacytoid. Among them, the plasmacytoid cell type appears to have a predilection for the oral cavity, especially the palate. We presented a 32-year-old man with plasmacytoid myoepithelioma arising in the soft palate, together with a brief discussion of the clinicopathologic features and differential diagnosis in the light of the literature.