Plasticity of committed mouse B cells has been demonstrated by inactivation of the B-cell commitment transcription factor PAX5, resulting in loss of the B-cell phenotype and differentiation into various hematopoietic lineages. Furthermore, mature mouse B cells could be reprogrammed into macrophages by overexpression of myeloid-specific transcription factors. Here, we report that aberrant activity of the transmembrane receptor, Notch1, interferes with the B-lymphoid phenotype of mature human germinal center-derived B cells in Hodgkin lymphoma, so called Hodgkin and Reed-Sternberg cells. They have lost the B-cell phenotype despite their mature B-cell origin. Notch1 remodels the B-cell transcription factor network by antagonizing the key transcription factors E2A and early B-cell factor (EBF). Through this mechanism, B lineage-specific genes were suppressed and B lineage-inappropriate genes were induced. We provide evidence that absence of the Notch inhibitor Deltex1 contributes to deregulated Notch activity in Hodgkin and Reed-Sternberg cells. These data suggest that Notch activation interferes with dedifferentiation of neoplastic B cells in Hodgkin lymphoma.

Netrin-1, a laminin-related protein, is known to be involved in the nervous system development. Recently, Netrin-1's involvement in other processes such as cell adhesion, motility, proliferation, and differentiation that are important for the development of epithelial tissues has been described. In addition, Netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated-5 homolog, have been linked to apoptosis and angiogenesis. Since these properties are essential for tumor development, Netrin-1 and its receptors have been reported to promote tumorigenesis in many types of cancers. Here, we review the Netrin-1 mediated regulation of cancer, its potential use as a biomarker, and the targeting of the Netrin-1 pathway to treat cancers.

Recent years have seen the start of treatment of metastatic castration-resistant prostate cancer with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT), especially 177 Lu-PSMA-617. However, PRLT has side effects on the salivary glands that limit the safety of the treatment. The current study aimed to show the effect of external cooling with ice packs on 177 Lu-PSMA-617 uptake by the parotid glands (PGs). Methods:The study included 19 patients (mean age, 72.9 y) with metastatic castration-resistant prostate cancer who had been referred for the first time for 177 Lu-PSMA-617 treatment and underwent pretreatment 68 Ga-PSMA-11 PET/CT. Before the initiation of PRLT, the SUV max and SUV mean of the right and left PGs were measured on 68 Ga-PSMA PET/CT. Frozen ice packs were then affixed over the right PG of each patient for approximately 5 h; 1 h after they were affixed, PRLT was administered. At 4 h after PRLT, head-and-neck SPECT/CT was performed, and at both 4 and 24 h after PRLT, whole-body planar scintigraphy was performed. Regions and volumes of interest were applied for the right and left PGs, and the counts and volumes were determined. Results: Before PRLT, 68 Ga-PSMA-11 PET/CT showed no significant difference in SUV max or SUV mean between the right and left PGs (P . 0.05). At 4 and 24 h after PRLT, planar imaging showed no significant difference in counts between the cooled and noncooled PGs (P . 0.05). Furthermore, at 4 h after PRLT, SPECT/CT showed no significant difference in counts or volumes between the cooled and noncooled PGs (P . 0.05). Conclusion: External cooling does not reduce uptake of 177 Lu-PSMA-617 by the PGs.

Background: Lymph node involvement is an important prognostic factor in patients with gastric cancer. The aim of this study was to determine the prognostic significance of metastatic lymph node ratio (MLNR) and compare it to the number of lymph node metastasis in pN3 gastric cancer. Methods: We retrospectively analyzed 207 patients with pN3 gastric cancer who had undergone radical gastrectomy. Prognostic factors and MLNR were evaluated by univariate and multivariate analysis. Results: An MLNR of 0.75 was found to be the best cut-off value to determine the prognosis of patients with pN3 gastric cancer (p = 0.001). The MLNR was significantly higher in patients with large-sized and undifferentiated tumors, vascular, lymphatic and perineural invasion, and total gastrectomy. In multivariate analysis, MLNR (p = 0.041), tumor differentiation (p = 0.046), and vascular invasion (p = 0.012) were found to be independent prognostic factors for disease-free survival, while both MLNR (p < 0.001) and pN stage (p = 0.002) were independent prognostic indicators, as was tumor size, for overall survival. There was significant difference with respect to the recurrence patterns between MLNR groups. Lymph node and peritoneal recurrences were significantly higher in patients with MLNR > 0.75 compared to the MLNR < 0.75 group (p < 0.05). However, recurrence patterns were similar between pN3a and pN3b. Conclusion: Our results showed that MLNR was a useful indicator to determine the prognosis and recurrence patterns of patients with radically resected gastric cancer. Moreover, MLNR is a beneficial and reliable technique for evaluating lymph node metastasis.

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Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL) was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide) chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

e14618 Background: Wnt signal transduction pathway plays an important role in carcinogenesis. Wnt signal transduction pathway is a key component of the β-catenin-TCF / LEF family of transcription factors interact with and activate the transcription of Wnt target genes. The aim of this study is to evaluate the prognostic value of β-katenin and LEF-1 expression in patients with operable gastric cancer and the relationship between demographic and histopathological variables. Methods: In this study, 82 gastric cancer patients treated with adjuvant treatment after operation and followed in Oncology Department between 2006-2010 were included. β-katenin and LEF-1 expression were examined by immunuhistochemical analysis in paraffin embedded tumor tissues of the patients. Results: In this study, median age was 56 (26-81) years and median follow up was 19 (4-61) months. Performance status (ECOG PS) were 0-1 in all patients. Men/women ratio was 53/29 (64.6/35.4%). Median disease free survival (DFS) time was 17 months (SE:3 95% CI: 11-23) in 19 months of follow up. 3 years DFS rate was 39.7%. In all patients group, median overall survival (OS) time was 28 months (SE:4 95% CI: 20-36) and 3 years OS rate was 41,2%. There was no statistical correlation between β-catenin and LEF-1 expression and age, gender, performance status, tumor localization, T and N stage, lymphovascular, perinoral invasion, grade and operation type (>0.05). In addition, there was also no correlation between β-catenin and LEF-1 expression. According to univariate analysis, we did not find significant effect on age, gender, T stage, lymphovascular, perinoral invasion, grade and operation type on overall survival (p>0.05). Good performans status (ECOG 0), tumor infiltration without diffuse type like linitis plastica, and lower N stage had positive effect on survival (p=0.04, 0.033 and 0.005, respectively). In multivariate cox regression analysis, only N stage was found as an independent prognostic factor (p<0.05). Conclusions: In this study group, we found that the only N stage as an independent prognostic factor. Demographic features of the patients, histopathological characteristics other than N stage, β-catenin and LEF-1 prognostic effects have not been shown.

The aim of this study was to investigate the predictive and prognostic value of PLR, and the relationship between PLR and tumor localization.A total of 229 patients with de-novo metastatic CRC were retrospectively analyzed. The cutoff value for PLR was defined by the receiver operating characteristic (ROC) curve analysis and threshold value of 196.5 as best cut-off value was found.The higher rate of BRAF mutation was significantly detected for patients with PLRhigh (> 196.5) compared to those with PLRlow (≤196.5) (P = .001). PLR was significantly higher in tumors located on the right colon (P = .012). PLR, tumor localization, the presence of surgery for primary tumor, the presence of curative surgery, the presence of metastasectomy for progression-free survival (PFS) and PLR, gender, BRAF mutation, tumor localization, the presence of surgery for primary tumor, the presence of metastasectomy for overall survival (OS) were found to be prognostic factors by univariate analysis. Multivariate analysis showed that PLR, the presence of curative surgery and the presence of metastasectomy for both PFS and OS were found to be independent prognostic factors. Moreover, a logistic regression analysis indicated that PLR and tumor localization were found to be an independent factors for predicting response to systemic treatment (P < .001 and P = .023 respectively).Our results showed that pretreatment PLR was readily feasible and simple biomarker predicting response to treatment and survival, in addition it was significantly associated with tumor localization.