Schannoma cells induce a tumor-cell-specific cytotoxic- T-cell response upon transplantation into syngeneic rats but escape elimination through the secretion of immunosuppressive factors

Tumor cells often express antigens that can be recognized by the immune system. Despite induction of an immune response, the tumor cells escape their elimination. We have studied the mechanisms and factors which mediate these events in a syngeneic tumor model. NV2Cd rat schwannoma cells were transplanted into BDIX rats. After injection of 10⁷ to 2 × 10⁷ cells, tumors grew very slowly for 10 to 12 days. After that time, rapid growth was observed. The tumors consisted of compact areas of spindle-shaped cells with small cysts, many blood vessels and central necrotic areas. During tumor growth, the number of spleen cells and T lymphocytes increased, and cytotoxic T cells with specificity for the NV2Cd tumor cells were detected. The strong specific cellular immune response did not prevent the increase in tumor volume. We studied the biological activity of the fluid present in the cysts of the tumor. At a concentration of 1 ng to 10 μg protein per ml, the cyst fluid inhibited the proliferation of splenic T lymphocytes and B lymphocytes and of lymphoma cells, but enhanced the proliferation of NV2Cd tumor cells. The cyst fluids contain the immunosuppressive transforming growth factors (TGF)-β1, -β2 and -β3, also the vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Antibodies directed against TGF-β relieved the suppression of T-cell growth by cyst fluid, but did not influence the proliferation of NV2Cd cells. The growth-modulating factors present in the tumor cyst fluid were also detected in conditioned medium from NV2Cd cells cultured in vitro. Our data suggest that tumors can escape the cellular immune response by the production of factors that inhibit lymphocytes. They also enhance their own growth environment by secreted factors. Int. J. Cancer 70:542–550. © 1997 Wiley-Liss Inc.     

Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy : A multicenter randomized, double-blind, placebo-controlled trial

BACKGROUND:

The medical community lacks results from prospective controlled multicenter studies of the diagnostic efficacy of 5‐aminolevulinic acid (5‐ALA) cystoscopy on tumor recurrence in patients with superficial bladder tumors.

METHODS:

A prospective randomized, double‐blind, placebo‐controlled study was conducted in 370 patients with nonmuscle‐invasive urinary bladder carcinoma who received either 5‐ALA (n = 187) or a placebo (n = 183) intravesically before cystoscopy. Each group underwent cystoscopy under visible white light and under fluorescent light followed by transurethral tumor resection. The primary study objective was to evaluate the 12‐month recurrence‐free survival.

RESULTS:

Slightly more patients with tumors were detected by using 5‐ALA than by using the placebo (88.5% vs 84.7%). The mean numbers of tumor specimens per patient were 1.8 (5‐ALA) and 1.6 (placebo). Intrapatient comparison of fluorescent light versus white light cystoscopy in patients randomized to receive 5‐ALA showed a higher tumor detection rate with fluorescent light than with white light cystoscopy. In patients receiving 5‐ALA cystoscopy, the percentage of lesions that would not have been detected in these patients by white light cystoscopy ranged between 10.9% (pT1) and 55.9% (atypia). Progression‐free survival was 89.4% (5‐ALA) and 89.0% (placebo) (P = .9101), and recurrence‐free survival 12 months after tumor resection was 64.0% (5‐ALA) and 72.8% (placebo) (P = .2216).

CONCLUSIONS:

In comparison to the placebo, 5‐ALA cystoscopy did not increase the rates of recurrence‐free or progression‐free survival 12 months after tumor resection. Although more tumors per patient were detected in the 5‐ALA group, the higher detection rate did not translate into differences in long‐term outcome. Cancer 2011. © 2010 American Cancer Society.     

Ivor-Lewis Esophagectomy With and Without Laparoscopic Conditioning of the Gastric Conduit

Background

Anastomotic leakage is still the major surgical complication following transthoracic esophagectomy with intrathoracic esophagogastrostomy (Ivor-Lewis procedure). Modifications of this standard procedure aim to reduce postoperative morbidity and mortality.

Methods

In this retrospective analysis of a 12-year period, 419 patients who had an Ivor-Lewis (IL) procedure for esophageal carcinoma were included. Due to modifications of the standard procedure, two different groups were compared with respect to their mortality and anastomotic leakage rate. In 181 patients (43.1%), esophagectomy and gastric reconstruction was performed as a one-stage procedure (classical IL group). Two hundred thirty-eight patients (56.9%) underwent a modified IL procedure that included minimally invasive gastric mobilization and a two-stage operation following ischemic conditioning of the gastric conduit.

Results

The hospital mortality rate was lower in the modified IL group without statistical significance (2.9 vs. 6.1%). Thirty-five anastomotic leaks were diagnosed postoperatively, 17 in the classical IL group (9.4%) and 18 in the modified IL group (7.6%). The rate of late leakages (after the 10th postoperative day) was higher in the modified IL group. Septic complications and mortality following anastomotic leakage were less frequent in the modified IL group. Leaks in the classical IL group predominantly required rethoracotomy, whereas leaks of the modified IL group were sufficiently treated with endoscopic stenting.

Conclusions

Surgical modifications of the classical IL procedure, including a minimally invasive approach and ischemic conditioning of the gastric conduit, seem to reduce postoperative morbidity and mortality. However, due to the retrospective design of this study, the impact of other factors influencing the outcome cannot be ruled out.     

Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease

A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains “global cognitive functioning,” “memory,” “working memory,” “attention,” and “executive function.” These domain‐specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN‐DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa‐equivalence dosage (LED) and axial subscore of the UPDRS in the off‐medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN‐DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN‐DBS. © 2010 Movement Disorder Society     

Designer T cells by T cell receptor replacement

T cell receptor (TCR) gene transfer is a convenient method to produce antigen-specific T cells for adoptive therapy. However, the expression of two TCR in T cells could impair their function or cause unwanted effects by mixed TCR heterodimers. With five different TCR and four different T cells, either mouse or human, we show that some TCR are strong--in terms of cell surface expression--and replace weak TCR on the cell surface, resulting in exchange of antigen specificity. Two strong TCR are co-expressed. A mouse TCR replaces human TCR on human T cells. Even though it is still poorly understood why some TCRalpha/beta combinations are preferentially expressed on T cells, our data suggest that, in the future, designer T cells with exclusive tumor reactivity can be generated by T cell engineering.     

Pathohistological classification systems in gastric cancer:Diagnostic relevance and prognostic value

Several pathohistological classification systems exist for the diagnosis of gastric cancer.Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics,disease specific criteria and overall outcome.It is still controversial as to which classification system imparts the most reliable information,and therefore,the choice of system may vary in clinical routine.In addition to the most common classification systems,such as the Laurén and the World Health Organization(WHO)classifications,other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients.In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer,there is no sole classification system that is consistently used worldwide in diagnostics and research.However,several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making,which underlines the importance of a reliable classification system for gastric cancer.The latest results from gastric cancer studies indicate that it might be useful to integrate DNA-and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance.This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.     

Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival

Gastric Cancer - Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the...     

Endothelial Notch1 Activity Facilitates Metastasis

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