Browsing by Subject "Cancer staging"

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Open Access
Adjuvant autologous melanoma vaccine for macroscopic stage III disease: survival, biomarkers, and improved response to CTLA-4 blockade
(Hindawi Limited, 2016) Lotem, M.; Merims, S.; Frank, S.; Hamburger, T.; Nissan, A.; Kadouri, L.; Cohen, J.; Straussman, R.; Eisenberg, G.; Frankenburg, S.; Carmon, E.; Alaiyan, B.; Shneibaum, S.; Ayyildiz, Z. O.; Isbilen, M.; Senses, K. M.; Ron, I.; Steinberg, H.; Smith, Y.; Shiloni, E.; Gure, A. O.; Peretz, T.
Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.
Open Access
Colon cancer associated transcript-1 (CCAT1) expression in adenocarcinoma of the stomach
(Ivyspring International Publisher, 2015) Mizrahi, I.; Mazeh, H.; Grinbaum, R.; Beglaibter, N.; Wilschanski, M.; Pavlov, V.; Adileh, M.; Stojadinovic, A.; Avital, I.; Gure, A. O.; Halle, D.; Nissan, A.
Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Methods: Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Results: Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). Conclusion: CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance.
Open Access
Metastasis suppressor proteins in cutaneous squamous cell carcinoma
(Elsevier, 2016-07) Bozdogan, O.; Vargel, I.; Cavusoglu, T.; Karabulut, A. A.; Karahan, G.; Sayar, N.; Atasoy, P.; Yulug, I. G.
Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research.
Open Access
Phased-array MRI of canine prostate using endorectal and endourethral coils
(John Wiley & Sons, Inc., 2003) Yung, A. C.; Oner, A. Y.; Serfaty, J-M.; Feneley, M.; Yang, X.; Atalar, Ergin
A four-channel phased array consisting of one surface coil, two endorectal coils, and one flexible endourethral loop coil was designed for MRI of the canine prostate. The endorectal coils provide high signal in the posterior region of the prostate, while the endourethral and surface coils are sensitive to the central and anterior regions of the prostate. Gel phantom experiments indicate that the proposed phased-array configuration generates 15 times more signal-to-noise ratio (SNR) than a combination of two surface coils and one endorectal coil within the posterior region of the prostate; the performance of the two configurations is comparable near the anterior prostate surface. Ultimate intrinsic SNR (UISNR) analysis was used to compare the proposed phased array's performance to the best possible SNR for external coils. This analysis showed that the proposed phased array outperforms the best-case external coil within the posterior and central regions of the prostate by up to 20 times. In canine experiments in vivo, high-resolution fast spin-echo (FSE) images of the prostate were obtained with a pixel size of 230 μm obtained in 3 min 12 s. The proposed phased-array design potentially can be used to increase the accuracy of prostate cancer staging and the feasibility of MR-guided prostate interventions. © 2003 Wiley-Liss, Inc.
Open Access
PPAR-alpha L162V polymorphism in human hepatocellular carcinoma
(Turkish Society of Gastroenterology, 2008) Koytak, E. S.; Mızrak, D.; Bektaş, M.; Verdi, H.; Arslan-Ergül, Ayça; İdilman, R.; Çınar, K.; Yurdaydın, C.; Ersöz, S.; Karayalçın, K.; Uzunalimoğlu, Ö.; Bozkaya, H.
Background/aims: Several lines of evidence suggest that peroxisome proliferator-activated receptor alpha may be involved in hepatocarcinogenesis. L162V polymorphism of the peroxisome proliferator-activated receptor alpha gene enhances the transactivation activity of this transcription factor. The aim of this study was to determine the frequency and clinical correlates of peroxisome proliferator-activated receptor alpha L162V polymorphism in hepatitis virus-induced hepatocellular carcinoma. Methods: 90 hepatocellular carcinoma patients diagnosed at Ankara University Gastroenterology Clinic between January 2002 and July 2003 and 80 healthy controls with normal body mass index, blood chemistry and with negative viral serology were included. peroxisome proliferator-activated receptor alpha L162V polymorphism was determined by PCR-RFLP. Results: hepatocellular carcinoma etiologies were as follows: 56 HBV, 12 HBV+HDV, 22 HCV. Eighty-seven patients (97%) were cirrhotic, and 60 patients (67.5%) had advanced tumors. In 83 (92%) of 90 hepatocellular carcinoma patients, gene segment including polymorphic region could be amplified by PCR (50 HBV, 12 HBV+HDV, 21 HCV) and 6 of them (7.2%, all infected with HBV) had L162V polymorphism, while 2 (2.5%) of 80 controls had this polymorphism (p=0.162). This trend became more remarkable when only HBV (HBV+HDV)-infected patients were compared with controls (6/62, 9.7% vs. 2/80, 2.5%, respectively, p=0.071). Five of 6 patients with L162V had advanced disease. Conclusions: Peroxisome proliferator-activated receptor alpha L162V polymorphism tends to occur in HBV-induced epatocellular carcinoma and is absent in HCV-related epatocellular carcinoma. These findings may show clues for the existence of different carcinogenesis mechanisms in these two common etiologies. Frequent occurrence of advanced disease in patients with L162V polymorphism suggests a role for this polymorphism in tumor progression.
Open Access
Prognostic value of p53 gene mutations in a large series of node-negative breast cancer patients
(1998) Falette, N.; Paperin, M. P.; Treilleux, I.; Gratadour, A. C.; Peloux, N.; Mignotte, H.; Tooke, N.; Löfman, E.; Inganäs, M.; Bremond, A.; Ozturk, M.; Puisieux, A.
The most important subgroup of breast cancer patients for which reliable prognostic factors are needed are women without axillary lymph node involvement. Although overall, these patients have a good prognosis, it is known that 20-30% will experience a recurrence of the disease. To determine the prognostic significance of P53 tumor suppressor gene mutation, specimens from 113 primary breast cancers were evaluated for the presence of P53 alterations, as detected by cDNA sequencing of the entire coding sequence of the gene. The median follow-up for patients was 105 months. P53 gene mutation was an independent prognostic marker of early relapse and death. Our results suggest that P53 gene mutations could be an important factor to identify node-negative patients who have a poor prognosis in the absence of adjuvant therapy. Prospective studies should be designed to determine which therapy should be performed in this subgroup of patients.
Open Access
Quantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two groups of genes with coordinate expression
(BioMed Central, 2008) Avci, M. E.; Konu, O.; Yagci, T.
Background: SLIT-ROBO families of proteins mediate axon pathfinding and their expression is not solely confined to nervous system. Aberrant expression of SLIT-ROBO genes was repeatedly shown in a wide variety of cancers, yet data about their collective behavior in hepatocellular carcinoma (HCC) is missing. Hence, we quantified SLIT-ROBO transcripts in HCC cell lines, and in normal and tumor tissues from liver. Methods: Expression of SLIT-ROBO family members was quantified by real-time qRT-PCR in 14 HCC cell lines, 8 normal and 35 tumor tissues from the liver. ANOVA and Pearson's correlation analyses were performed in R environment, and different clinicopathological subgroups were pairwise compared in Minitab. Gene expression matrices of cell lines and tissues were analyzed by Mantel's association test. Results: Genewise hierarchical clustering revealed two subgroups with coordinate expression pattern in both the HCC cell lines and tissues: ROBO1, ROBO2, SLIT1 in one cluster, and ROBO4, SLIT2, SLIT3 in the other, respectively. Moreover, SLIT-ROBO expression predicted AFP-dependent subgrouping of HCC cell lines, but not that of liver tissues. ROBO1 and ROBO2 were significantly up-regulated, whereas SLIT3 was significantly down-regulated in cell lines with high-AFP background. When compared to normal liver tissue, ROBO1 was found to be significantly overexpressed, while ROBO4 was down-regulated in HCC. We also observed that ROBO1 and SLIT2 differentiated histopathological subgroups of liver tissues depending on both tumor staging and differentiation status. However, ROBO4 could discriminate poorly differentiated HCC from other subgroups. Conclusion: The present study is the first in comprehensive and quantitative evaluation of SLIT-ROBO family gene expression in HCC, and suggests that the expression of SLIT-ROBO genes is regulated in hepatocarcinogenesis. Our results implicate that SLIT-ROBO transcription profile is bi-modular in nature, and that each module shows intrinsic variability. We also provide quantitative evidence for potential use of ROBO1, ROBO4 and SLIT2 for prediction of tumor stage and differentiation status.