Association between Glutathione-S-Transferase and Gastric Carcinoma: A Case Control Study

Gastric carcinoma is the fourth most common cancer type and the second leading cause of cancer deaths worldwide. Every year, around 1 million new cases and 0.7 million deaths are caused due to gastric carcinoma. Gastrointestinal tract is involved in absorption and metabolism of toxic or potentially carcinogenic compounds which may be present in the food we eat. In this context, digestive tract may be considered as a major site of cancer in humans. Glutathione-S-Transferase (GST) is an important metabolizing enzyme, present in the epithelial cells of human GIT. As nearly all reactive, ultimate carcinogenic forms of chemicals are electrophiles, GST is substantially important as a mechanism for carcinogen detoxification. The present study was conducted to evaluate the role of GST in gastric carcinoma and analyse the level of serum GST in patients suffering from gastric carcinoma. METHODSThis is a case control study, conducted among 50 cases of gastric carcinoma and 50 age sex matched controls. Patients included in this study were diagnosed with gastric carcinoma, after clinical and histological examination. Circulating levels of GST were assayed in the in the serum of control group and in patients with gastric carcinoma, using standardized method. RESULTSMean GST activity in serum was significantly higher (p < 0001) in gastric carcinoma patients (8.24 ± 1.94) as compared to control (5.47 ± 0.52). After chemotherapy (12.34 ± 1.05) the activity of GST was significantly higher (p < 0001) than before chemotherapy (10.23 ± 2.12). The generation of free radicals is as reflected by increased GST and GST-π activity in carcinoma cases. CONCLUSIONSSerum GSTs measurement in plasma may be a useful tumour marker in stomach cancer and serum GSTs activity might be helpful in predicting the response of chemotherapy in advanced stages of cancer. GST values are helpful in predicting the radiation response. Overexpression of GST in neoplasia may be causal, allowing replicative advantage, or casual, accompanying clonal expansion. The major limitation to its widespread use is the time needed for doing the assay and until this is overcome it will remain primarily a research tool.

Study of ovarian cancer at a tertiary care centre

Background: Despite major advances in case management, ovarian cancer continues to have the highest case fatality rate of all gynaecologic malignancies. There is paucity of meaningful screening and diagnostic protocols. Present study was planned with the objective of assessment of the prevalence of ovarian cancer and the associated risk factors at a tertiary care centre.Methods: The present prevalence study was conducted at a tertiary care government hospital and entailed analysis of data of 73 patients of ovarian cancer. All the participants were subjected to comprehensive history taking, followed by general, systemic, per-speculum and per-vaginal examination. Serum tumour markers of the patients were assessed. Imaging studies including ultrasound, CT or MRI abdomen/pelvis were done as per need. Final diagnosis was confirmed on histopathology and the cases were classified according to histological classification of World Health Organization.Results: Majority (41, 56.2%) were aged more than 45 years and above, most of them with one to two previous issues (64.3%). The disease was observed to be more common in postmenopausal women (65, 89%). Three fourth participants had negative family history of ovarian or breast cancer. Out of 73 patients, 31 had value of CA 125 between 150-400 U/mL and 42 had values >400 U/mL. Epithelial ovarian cancer (serous- 33, 45.2%, mucinous- 18, 24.7%) was observed to be the commonest histological type.Conclusions: To diagnose ovarian tumours early using multipronged approach with focussed risk factor identification and screening with CA-125 is very important and is strongly recommended.

Role of serum CA 19-9 as a tumor marker in TCC bladder

Background: There is a dearth of reliable blood and urine markers for transitional cell carcinoma of urinary bladder. CA 19-9 is a well-known marker for gastrointestinal malignancies and is being investigated for other malignancies including carcinoma bladder. In this prospective study, we evaluated the role of serum CA 19-9 as a tumor marker and correlated its level with tumor grade and stage.Methods: One hundred and fifteen patients with transitional cell carcinoma of urinary bladder and 69 healthy volunteers, as controls were included in the study. Preoperative blood sample was analysed for level of CA 19-9 using ELISA kit (normal - 0 U/ml to 37U/ml) and were correlated with grade and TNM stage of tumor.Results: The range of the control group is 2-38U/ml (mean: 17.67±9.68U/ml); TCC group is 1-94U/ml (mean: 37.12±31.52U/ml) (p=0.304). When CA 19-9 level >37IU/ml was taken as cut-off for a positive test, sensitivity of detecting T3 disease, T4 disease, MIBC, presence of node and high grade tumour were 80%, 75%, 70.3%, 78% and 57.8% respectively. However, there was a statistically significant increase in levels of CA19-9 in relation to higher grade (<0.001), presence of muscle invasion (<0.001), T stage (<0.001) and N stage (<0.001).Conclusions: Serum CA19-9 is almost invariably raised in patients with high grade and invasive disease. Thus, it has a place as a prognostic marker rather than as a diagnostic tool due to its low sensitivity for TCC bladder.

Expression and clinical significance of Gli1 in peripheral blood and cancer tissues of gastric cancer patients / 中华普通外科杂志

Objective To explore the relationship and clinical significance of Gli1 expression in peripheral blood and cancer tissues of gastric.Method 95 gastric cancer patients were recruited as surgery group,and 40 recurrent gastric cancer patients were recruited as recurrent group.50 normal subjects were recruited as control group.Paraffin specimens of gastric cancer tissues and gastric mucosa adjacent to cancer were collected to test expression of Gli1 protein.ELISA was applied to test Gli1 in peripheral blood.Results Levels of Gli1 in peripheral blood of preoperative surgery group were higher than in control group [(9.21 ± 1.37) ng/ml vs.(0.79 ±0.18) ng/ml,t =43.193,P ＜0.001].Post-up Gli1 decreased significantly to the level of control group (t =0.722,P =0.472).Levels of Gli1 in peripheral blood of recurrent group were higher than that in preoperativesurgery group (t =14.575,P ＜ 0.001).Gli1 protein in cancer tissues was higher than that in adjacent gastric mucosa (t =33.471,P ＜0.001),and Gli1 protein in cancer tissues of surgery group was higher than that in cancer tissues of recurrent group (t =8.808,P ＜0.001).Conclusion In postoperative gastric cancer patients increased Gli1 level in peripheral blood and cancer tissues predicts recurrence.

Determinants of lymph node status in women with breast cancer: A hospital based study from eastern India.

Background & objectives: Number of metastatic lymph nodes has a strong prognostic value in the course of breast cancer treatment, morbidity and mortality. This study was undertaken to determine the association between axillary lymph node metastasis and several variables such as age, tumour size, grade, lymphovascular invasion, oestrogen and progesterone receptor expression and HER2/neu status in patients with breast cancer. Methods: In this study 426 (with complete information on study variables) patients with breast cancer on treatment during March 2010 to December 2013, were analyzed. TNM (tumour node matastasis) staging was evaluated. The histological grading of tumours was done according to modified Bloom-Richardson Grading System. The immunophenotype of the tumour was determined as the expression of oestrogen (ER) and progesterone (PR) receptors and HER2/neu status. Univariate and multivariate analyses were carried out to determine the independent predictors of metastatic lymph node. Results: Among the studied patients, 44.36 per cent (189 of 426) of the patients had nodal metastases. Tumour histology, tumour grade, size and lympho-vascular invasion were related with node positivity. On univariate analysis, age, menopause, hormone receptor status did not relate with the node metastasis. Age, tumour grade, tumour size, lympho-vascular invasion and HER2/neu expression was likely to be associated with the number of lymph node metastasis. Interpretation & conclusions: The lymph node status was associated with clinical stage, tumour grade, tumour histology and HER2/neu status. These factors may be used for better management of such patients.

Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer

PURPOSE: To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. MATERIALS AND METHODS: We included 223 patients who received staging laparotomy and were diagnosed with stage IIC-IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. RESULTS: The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). CONCLUSION: Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.

Annual Report on External Quality Assessment Scheme for Immunoassay Tests in Korea (2014)

In 2014, two external quality assessment trials were performed on 13 test items grouped in four categories. The laboratories procured the materials for the first and second trials on 13 May 2014 and 11 November 2014, respectively. The trials were performed on 13 test items, including tumour markers, thyroid hormones, cardiac marker troponin (troponin T or troponin I), and procalcitonin as a new biomarker for immunoassay methods. The bone marker carboxy-terminal collagen crosslinks (CTX) has been replaced by procalcitonin this year because only a limited number of institutions used it. External quality surveys of the 13 immunoassay test items with 8 control materials were performed as scheduled. The 13 control materials included six tumour markers, alpha-fetoprotein, carcinoembryonic antigen, carcinoma antigen 125, carbohydrate antigen 19-9, human chorionic gonadotrophin, and prostate specific antigen, as well as five thyroid markers, thyroid hormone 3 (T3), T4, thyroid stimulating hormone, free T4, and thyroglobulin. This year, procalcitonin has been introduced as a new biomarker in addition to troponin, which was introduced last year. Five homemade pooled sera and three commercial control sera were used as survey materials. The MAS Tri-point Liquimmune level 3 (Medical Analysis Systems Inc., USA) was used for controls of thyroid hormones, while Elecsys PreciControl Varia and Elecsys PreciControl Troponin (Roche, Germany) were used for controls of the new biomarkers procalcitonin and troponin, respectively. In the external quality assessment by the Immunoassay Subcommittee, 712 institutions participated in the first trial survey (response rate 97.9%), while 715 participated in the second survey (response rate 97.9%). The quality of the participating laboratories seems to be continuously improving compared to the results of their peers. Additionally, this year procalcitonin has been introduced as a new biomarker instead of the CTX, which was used in 2013, while thyroglobulin and troponin-T/troponin-I, which were used for the 2013 samples, continue to be used in surveys by the Immunoassay Subcommittee.

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

Combined Assessment of TGF-beta-1 and Alpha- Fetoprotein Values Improves Specificity in the Diagnosis of Hepatocellular Carcinoma and Other Chronic Liver Diseases in Malaysia

Transforming growth factor beta-1 (TGF-β-1) is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. The main aim of this study was to determine whether TGF-β-1 or alpha fetoprotein (AFP) or the combination of the two is a better indicator for hepatocellularcarcinoma (HCC). Serum TGF-β-1 and AFP were measured by ELISA in 40 healthy subjects, 23 patients with hepatocellular carcinoma (HCC), 70 patients with hepatitis B, 26 patients with hepatitis C and 16 patients with liver cirrhosis (LC). Patients with liver diseases showed significantly higher serum TGF-β-1 values (>3 fold) compared to control subjects. As for serum AFP, significant elevation was only observed for HCC cases. Serum TGF-β-1 exhibited higher percent sensitivity compared to serum AFP in all liver diseases. Combination of serum TGF-β-1 and AFP increased specificities in all cases studied. In conclusion, serum TGF-β-1 is a more sensitive marker for HCC when compared to serum AFP and its specificity is increased when combined with serum AFP.

Evaluation of clinical significance of a new tumour marker, cyfra21-1, in diagnosios of squamous cell cervical cancer: A preliminary study.

The purpose of this study was to evaluate the significance of Cyfra21-1 as a new tumour marker in the diagnosis of squamous cell cervical cancer. Cyfra21-1 enzyme immunoassay was used for the determination of Cyfra21-1 levels in sera of 120 cervical cancer patients and 17 normal control cases. According to the International Federation of Gynaecology and Obstetrics (FIGO) stage, these cervical cancer patients were staged at CIN or CIS, stage I, stage II and stage III (19,17,42 and 42 cases, respec-tively). The 17 normal controls comprised five healthy women and 12 patients with benign gynaecological diseases and tumours that had presented negative results from Papanicolauo smears. We found that the normal value of serum Cyfra21-1 level was 0.99 + 0.28 ng/ml (mean+ 2SE). Serum Cyfra21-1 levels of the cervical cancer patients increased depending on the severity of the disease. Moreover, the Serum Cyfra12-1 levels of only the patients with FIGO stage III were significantly higher than those of the normal controls, and the patients in CIN or CIS and stage I (p=0.0055). The serum Cyfra21-1 levels of the normal controls the patients in CIN or CIS, stage I, and stage II differed insignificantly from one another. This test showed a sensitivity of 65 per cent and specificity of 82 per cent. The ROC curve was used to determine the cut-off value (1.3 ng/ml) of the increased levels. A prospective study should be further performed to evaluate the usefulness of this marker as a non-invasive modality for diagnosis and monitoring cervical cancer in the future.