Outcome In Gastric Carcinoma Research Articles

Photothermal/Photodynamic Therapy with Immune‐Adjuvant Liposomal Complexes for Effective Gastric Cancer Therapy

AbstractA diagnosis and therapeutic strategy for gastric cancer is developed herein by combining thermosensitive liposomal (TSL)‐based photothermal/photodynamics therapy (PTT/PDT) with chemotherapy and adjuvant immunotherapy. IR820, a photothermal agent, paclitaxel (PTX), an antitumor drug, and imiquimod (R837), a Toll‐like‐receptor‐7 agonist, are coencapsulated into a TSL drug delivery system. These formed PTX‐R837‐IR820@TSL complexes exhibit excellent optical properties, good dispersibility, and stability. Under NIR light irradiation, the measurement of singlet oxygen production and thermal efficiency indicate promising potential of PTX‐R837‐IR820@TSL complexes for PTT and PDT. Confocal microscopy and small animal NIR imaging demonstrate tumor targeting ability of the liposomal complexes to gastric cancer cells. In vitro cell viability assays and in vivo animal experiments show prominent antitumor efficiency of PTX‐R837‐IR820@TSL complexes upon NIR light irradiation. This excellent therapeutic efficacy is attributed to the simultaneous chemotherapy and PTT/PDT. Furthermore, the liposomal complexes under NIR irradiation would ablate tumors to generate a pool of tumor‐associated antigens, which is able to promote strong antitumor immune responses in the presence of those R837‐containing liposomal complexes acted as adjuvant. These results indicate that the multifunctional liposomal complexes could realize a remarkable synergistic therapeutic outcome in gastric carcinoma.

Management and outcome of gastric carcinoma in a tertiary health care centre

Background: Cancer is a biggest burden of modern society. Gastric cancer is the second leading cause of cancer death in the world. The objective of study was to study the clinico pathological features and management and outcome of gastric cancer patients admitted to hospital.Methodology: A prospective descriptive study was conducted in 50 diagnosed patients of gastric adenocarcinoma using pre-designed questionnaire collecting information on demographics, stage and site of tumor, clinical history, duration of stay etc.Results: There were 50 patients with male to female ratio 2.5: 1 with mean age of 62+/- 7.89 SD. 88% patients had tumor at antrum region. 25 (50%) and 28 (56%) patients gave h/o smoking and alcohol consumption respectively with 23 (46%) had biopsy positive for H. pylori. Of the gastrectomies, 41 (82%) study subjects were managed by curative surgeries. The overall hospital stay in stage II gastric adenocarcinoma was 6-8 days and 7-8 days in stage III (p=0.16).Conclusion: systematic population screening program of upper gastrointestinal endoscopy should be established to detect early cases of gastric cancer show that treatment may be initiated early which has impact on survival for this dreaded diseases.

Overexpression of YEATS4 Contributes to Malignant Outcome in Gastric Carcinoma

Kiuchi, Jun MD; Komatsu, Shuhei MD, PhD, FACS; Shoda, Katsutoshi MD, PhD; Kosuga, Toshiyuki MD, PhD; Konishi, Hirotaka MD; Shiozaki, Atsushi MD, PhD; Kubota, Takeshi MD, PhD; Fujiwara, Hitoshi MD; Okamoto, Kazuma K. MD; Otsuji, Eigo MD Author Information

Overexpression of SETDB1 Is Related to Poor Outcome in Gastric Carcinoma

Overexpression of SETDB1 Is Related to Poor Outcome in Gastric Carcinoma

Overexpression of SETDB1 in relation to poor outcome in gastric carcinoma.

71 Background: SETDB1 is a Histone H3 lysine 9-specific Methyl Transferase belonging to the SET domain. In this study, we tested whether SETDB1 acts as a cancer-promoting gene through its overexpression in gastric cancer (GC). Methods: We analyzed5 GC cell lines and 135 primary GC samples curatively resected in our hospital. Results: Overexpression of the SETDB1 protein was detected in all GC cell lines and primary GC samples (115/135 cases, 85%). Knockdown of SETDB1 using specific siRNA inhibited the proliferation, migration and invasion. Overexpression of the SETDB1 was significantly correlated with lymphatic invasion, deeper tumor depth and higher recurrence rate. Patients with SETDB1-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0041, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SETDB1 was independently associated with worse outcome (P = 0.0178, HR 3.1 (1.20-9.83)). Conclusions: These findings suggest that SETDB1 has a crucial role in tumor cell proliferation and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.

Development of a quantitative PCR assay to evaluate HER2 status of Gastric carcinoma in a cohort of Sri Lankan patients

Introduction Human epidermal growth factor receptor2 (HER2) protein over expression and/or HER2gene amplification are/is linked to dismal outcome of Gastric carcinoma (GCa). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are key-methods to identify patients for HER2 targeted therapy. Drawbacks of both methods warrant novel-tests. Objective To determine whether quantitative Polymerase Chain Reaction (qPCR) could serve as a supplementary-method to evaluate HER2 status of GCa in a cohort of Sri Lankan patients and investigate correlation between HER2 assessed by different methods and clinicopathological features. Methods Twenty GCa-patients with known IHC-HER2 scores were evaluated. qPCR was performed for HER2 gene and Ameloid precursor protein (reference gene) in Formalin fixed paraffin embedded GCa tissue. Threshold values (Ct) were analyzed using Pfaffl-method to detect HER2 gene amplification. Results HER2positivity by IHC (protein) and qPCR (gene) were 20% and 35% respectively. Sensitivity and specificity of qPCR was 67% and 76% respectively and results were reproducible. HER2 protein positivity was correlated with Tumour TNM-stage and Lauren-histological types (P Discussion & Conclusion Discrepancies between HER2 positivity by IHC and qPCR were possibly due to transcription activation by other genes in the absence of HER2 gene amplification and the aberrant form of HER2 protein not detected by IHC. Studies also indicate a higher-proportion of IHC negative, but HER2gene amplified GCa by FISH. qPCR may be used as a supplementary-method for detection of HER2 status of GCa in local setting.

Application of a quantitative PCR assay to evaluate Human Epidermal Growth Factor Receptor - 2 status of Gastric carcinoma in a cohort of Sri Lankan patients

Introduction Human epidermal growth factor receptor2 (HER2) protein over expression and/or HER2 gene amplification is linked to dismal outcome of gastric carcinoma (GCa). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are key methods to identify patients for HER2 targeted therapy. Draw backs of both methods warrant novel tests. The objectives were to determine whether quantitative Polymerase Chain Reaction (qPCR) could serve as a supplementary method to evaluate HER2 status of GCa and investigate the correlation between HER2 assessed by different methods and clinicopathological features. Methodology Twenty GCa patients with known IHC-HER2 scores were evaluated. qPCR was performed for HER2 gene and Amyloid precursor protein (reference gene) in formalin fixed paraffin embedded GCa tissue. Threshold values (Ct) were analyzed using Pfaffl-method to detect HER2 gene amplification. Results HER2 positivity by IHC (protein) and qPCR (gene) were 20% and 35% respectively. Sensitivity and specificity of qPCR was 67% and 76% respectively and results were reproducible. HER2 protein positivity was correlated with TNM-stage and Lauren histological types (P Discussion Discrepancies between HER2 positivity by IHC and qPCR were possibly due to transcription activation by other genes in the absence of HER2 gene amplification and the aberrant form of HER2 protein not detected by IHC. Studies also indicate a higher proportion of IHC negative, but HER2 gene amplified GCa by FISH. Conclusion qPCR may be used as a supplementary method for evaluation of HER2 status in gastric carcinoma proven to be HER2 negative by immunohistochemistry.

Overexpression of denticleless E3 ubiquitin protein ligase homolog (DTL) is related to poor outcome in gastric carcinoma.

Denticleless E3 ubiquitin protein ligase homolog (DTL) has been identified in amplified region (1q32) of several cancers and has an oncogenic function. In this study, we tested whether DTL acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). We analyzed 7 GC cell lines and 100 primary tumors that were curatively resected in our hospital between 2001 and 2003. Overexpression of the DTL protein was detected in GC cell lines (4/7 cell lines; 57%) and primary GC tumor samples (42/100 cases; 42%). Knockdown of DTL using several specific siRNAs inhibited the proliferation, migration and invasion in a TP53 mutation-independent manner. Overexpression of the DTL was significantly correlated with lymphatic invasion, deeper tumor depth and higher recurrence rate. Patients with DTL-overexpressing tumors had a worse survival rate than those with non-expressing tumors in overall survival (P = 0.0498, log-rank test) and disease-free survival (P = 0.0324, log-rank test). In a multivariate analysis, DTL positivity was independently associated with a worse overall survival (P = 0.0104, hazard ratio 3.7 [1.36-10.1]) and disease-free survival (P = 0.0070 (hazard ratio, 3.9 (1.45-10.46)) following radical gastrectomy. These findings suggest that DTL overexpression plays a crucial role in tumor cell proliferation and highlights its usefulness as a prognosticator and potential therapeutic target in gastric cancer.

Novel prognostic score for patients with gastric carcinoma

Objective The lack of a simple criterion for gastric carcinoma creates a persistent challenge for clinicians trying to provide patients with useful prognostic information. The aim of this study was to identify baseline prognostic factors, and use this information to establish a simple criterion to predict outcome in gastric carcinoma.

Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma

BCL2L10 protein is an apoptosis-related member of the Bcl-2 protein family. The clinical significance of its expression in gastric carcinoma is poorly understood. The aim was to investigate BCL2L10 expression and its clinical and prognostic significance in gastric carcinoma patients. Immunohistochemistry, real-time polymerase chain reaction (PCR) and immunoblotting all revealed extensive loss of BCL2L10 expression in gastric cancer cells. The scaled BCL2L10 expression data was categorized into three groups (groups 0-2) to facilitate statistical analysis. A significant correlation was observed between the lower BCL2L10 expression group and shorter disease-free survival (P=1.956×10(-18)). Multivariate regression analysis showed that loss of BCL2L10 protein expression [P=4.883×10(-8), hazard ratio (HR)=0.252] is an independent prognostic predictor of gastric carcinoma. The receiver operator characteristic (ROC) curve showed that the area for BCL2L10 protein was 0.817 (P=8.331×10(-14)), indicating that loss of BCL2L10 protein expression is an excellent prognostic predictor of gastric carcinoma. Loss of BCL2L10 protein expression predicts poor clinical outcome in gastric carcinoma.

Pathological prognostic score as a simple criterion to predict outcome in gastric carcinoma

The aim of this study was to establish a simple criterion to predict prognosis of patients with gastric carcinoma. Two hundred four patients with gastric carcinoma, who had been treated with curative resection, were enrolled. One point was added for each category among four pathological factors of depth of tumor, lymph node metastasis, venous invasion, and lymphatic invasion. Pathological Prognostic Score (PPS) was determined by an aggregate of these points for each category. There existed a significant difference between survivals of patients with PPS 0 or 1 and 2 or 3 (P = 0.0002). Similarly, there also existed a significant difference between survivals of patients with PPS 2 or 3 and 4 (P = 0.010). PPS can be quite simple criteria to predict prognosis of gastric carcinoma with a strict stratification.

Expression of the Antiapoptosis Gene Survivin Predicts Poor Prognosis of Stage III Gastric Adenocarcinoma

This study was designed to determine the level of survivin expression and its clinical significance as a prognostic factor in Stage III gastric adenocarcinoma. We performed immunohistochemical staining for survivin, p53 and Bax in formalin-fixed, paraffin-embedded blocks from 157 surgically resected Stage III gastric cancer tissues. To determine the association with clinical course, we reviewed the patients' clinical records. Of the 157 gastric cancer tissues, 63 (40.1%) cases showed positive expression for survivin protein. There was no significant association between survivin expression and p53 or Bax. For clinicopathologic parameters, large tumor size was closely related to survivin expression (P < 0.05). The 5-year survival rate of patients with positive survivin expression was significantly lower compared with that for survivin-negative cancer patients (P < 0.05). Survivin and p53 were independent prognostic factors in Stage III gastric cancer. Survivin protein is an important predictive and prognostic parameter of poor outcome in gastric carcinoma.

MSI predicts favorable outcome in gastric carcinoma

MSI predicts favorable outcome in gastric carcinoma

P27Kip1 expression and survival in NO gastric carcinoma.

p27Kip1, a cyclin-dependent kinase inhibitor, is considered to be a tumor suppressor gene. Absent or reduced expression of the p27Kip1 protein has been reported being a negative prognostic marker in primary lung, breast, colon, bladder, and prostate carcinomas. p27Kip1 protein expression was evaluated in a series of 96 gastric carcinomas with no lymph node involvement (NO) to verify any impact on the clinical outcome. The analysis also considered the classic clinico-pathological parameters, such as age, sex, and depth of tumor invasion (pT). The most widely used classification systems for gastric carcinoma were adopted. The expression of p27pKip1 was related neither to the pT category nor to tumor histology. Kaplan-Meier analysis documented a significant impact of an advanced pT category (p < 0.0001) and p27Kip1-reduced expression (p < 0.0002) on survival. Multivariate analysis confirmed that the reduced p27Kip1 protein expression was a strong independent predictor of poor outcome, ranking second to the pT category only (p < 0.006 and p < 0.004 respectively). As reported for other neoplasms, the expression of p27Kip1 appears to be associated with the clinical outcome of gastric carcinoma.

Dimeric sialyl-Le x expression in gastric carcinoma correlates with venous invasion and poor outcome

Background & Aims: High expression of sialyl-Le x in tumors of different organs correlates with hematogenous metastasis and adverse outcome. Dimeric sialyl-Le x expression in gastric carcinoma was evaluated, and its prognostic significance within this setting was determined. Methods: Dimeric sialyl-Le x immunohistochemical expression in 97 gastric carcinomas was analyzed using the FH6 monoclonal antibody. Scoring was based on the percentage of immunoreactive cells: negative, low expression (≤25%), and high expression (>25%). Results: Immunoreactivity was observed in 45 cases (46.4%), encompassing 27 and 18 cases with low and high expression, respectively. Significant relationships were found between dimeric sialyl-Le x expression and venous invasion ( P = 0.0025) and histological classification ( P = 0.05). No correlation was observed with other clinicopathologic features. Patients with tumors showing high expression of dimeric sialyl-Le x had a significantly shorter survival time than those with low or no expression ( P = 0.03). By multivariate analysis, pathological TNM (pTNM) staging and venous invasion emerged as independent prognostic factors in the whole series. Within the group of patients with tumors in pTNM stages II and III, dimeric sialyl-Le x was the only independent prognostic factor. Conclusions: High expression of dimeric sialyl-Le x correlates with venous invasion and poor outcome in gastric carcinoma. GASTROENTEROLOGY 1998;114:462-470

Correlation of DNA ploidy, histopathology, stage and clinical outcome in gastric carcinoma

The determination of nuclear DNA ploidy from paraffin-embedded specimens was performed by flow cytophotometry on 277 surgically resected primary gastric carcinomas to assess the relationship of various pathological findings and DNA content with survival. The preparation of samples was performed by a modification of Hedley's technique and the staining method of Vindelov. Eighty-nine (32%) carcinomas were DNA diploid, 69 (25%) were DNA tetraploid, and 119 (43%) were DNA aneuploid. DNA non-diploid patterns were significantly associated with macroscopic ulcerative appearance, location of the tumour in the proximal stomach, histological grade, and advanced stage of tumour. Patients with DNA non-diploid cancers, and specifically DNA aneuploid cancers, exhibited significantly poorer survival than patients with DNA diploid tumours. These data support the prognostic value of tumour DNA content in patients with resected gastric carcinoma.